Heart failure following allogeneic haematopoietic stem cell transplantation  is a serious complication that requires early detection; however, the clinical implications of early-onset cancer therapy-related cardiac dysfunction (CTRCD) following allo-HSCT remain unclear. We investigated the determinants and prognostic impact of early-onset CTRCD in allo-HSCT recipients.The records of 136 patients with haematological malignancies who underwent allo-HSCT at our institute were retrospectively reviewed. Early-onset CTRCD was defined as a decrease in left ventricular ejection fraction (LVEF) of ≥10% and an LVEF of ≤53% within 100 days after HSCT.2) and severity of acute graft-versus-host disease (GVHD/grade) were independent indicators of early-onset CTRCD (OR (95% CI) 1.04 (1.00 to 1.07); p=0.032; OR (95% CI) 1.87 (1.19 to 2.95), p=0.004, respectively). The overall and primary disease death rates were significantly higher in allo-HSCT recipients with early-onset CTRCD than in those without early-onset CTRCD (HR (95% CI) 1.98 (1.11 to 3.52), p=0.016; HR (95% CI) 2.96 (1.40 to 6.29), p=0.005, respectively), independent of primary disease type, remission status and transplantation type.Early-onset CTRCD was diagnosed in 23 out of 136 included patients (17%), and the median duration from HSCT to CTRCD diagnosis was 24 (9–35) days. Patients were followed up for 347 (132–1268) days. In multivariate logistic regression analysis, cumulative doxorubicin dosage (each 10 mg/mSevere acute GVHD and higher cumulative anthracycline are two significant determinants of early-onset CTRCD. Early-onset CTRCD following allo-HSCT regulates survival in patients with haematological malignancies. Haematopoietic stem cell transplantation (HSCT) is a key treatment for refractory haematological malignancies.The preconditioning therapy and cell transplantation can cause various complications that make patient management difficult and worsen prognosis.Cancer therapy-related cardiac dysfunction (CTRCD) following HSCT can be a serious complication; however, the clinical implications of early-onset CTRCD in recipients of HSCT remain unclear.Severe acute graft-versus-host disease (GVHD) and higher cumulative anthracycline dose are independent risk factors for early-onset CTRCD after allogeneic HSCT.Early-onset CTRCD aggravates the prognosis of patients with haematological malignancies who have undergone allogeneic HSCT.Adequate immunosuppression for GVHD and preconditioning regimen alternative for anthracycline might preserve cardiac function.Monitoring of cardiac function and early intervention or prophylactic therapy for heart failure have a potential to improve prognosis of the patients who undergo allogeneic HSCT.Haematopoietic stem cell transplantation (HSCT) is an effective therapy for malignant and non-malignant haematopoietic disorders. Its outcomes have dramatically improved following advances in transplantation procedures and supportive care, resulting in more long-term survivors who have undergone HSCT.6 7Recently, left ventricular systolic dysfunction after cancer therapy, detected by a decrease in left ventricular ejection fraction (LVEF), was defined as cancer therapy-related cardiac dysfunction (CTRCD). Therefore, periodic monitoring of LVEF via echocardiography is recommended for patients with cancer.This single-centre, retrospective study included 416 consecutive patients who underwent allo-HSCT for haematological disease between January 2007 and December 2018 at Kyushu University Hospital. Patients with benign haematopoietic disease (n=65) in whom neutrophils were not engrafted after allo-HSCT (n=10), those whose echocardiograms had not been recorded prior to HSCT or within 100 days after HSCT (n=192), and those whose LVEF was ≤53% at the time of HSCT (n=13) were excluded; therefore, 136 patients were eligible for inclusion in the analysis . The medSince the aim of this study was to investigate the predictors of early-onset CTRCD and its impact on patient prognosis, candidates for the predictors of early-onset CTRCD included common cardiac risk factors, anthracycline dosage and haematologically important factors for the management of patients who underwent HSCT. Overall survival (OS), treatment-related mortality and death due to underlying diseases were evaluated as prognostic indicators. The protocol of this study was approved by the internal review board , and patient consent was obtained via an opt-out method. This was a retrospective observational study, and patients or the public could not be involved in the design, conduct, reporting or dissemination plans of our study. All procedures performed in this study were in accordance with the principles of the updated Declaration of Helsinki (2013).Growing evidence suggests that cardiooncology is a contemporary, diverse and challenging field of clinical science, and terminology relating to this field is somewhat confusing; therefore, we defined the terminology used in this study.Early-onset CTRCD was defined as CTRCD occurring within 100 days after allo-HSCT; CTRCD was defined as a decrease in LVEF by ≥10% from baseline LVEF and an LVEF of ≤53% after HSCT, irrespective of baseline LVEF.Cardiac risk factors include diabetes, hypertension, dyslipidaemia and current smoking.14 15The disease status of haematological malignancies evaluated at the time of HSCT was categorised as complete remission (CR) or non-CR, irrespective of the status following prior HSCT. Disease relapse was defined as a haematologically detected relapse. Acute GVHD was defined as GVHD occurring within 100 days after HSCT and graded according to the standard criteria.Continuous variables are presented as medians (IQR) and compared between groups using the Mann-Whitney U test. Discrete variables were analysed with a contingency table using Fisher’s exact test. Patient characteristics were analysed using logistic regression analysis. Additionally, multiple logistic regression analyses were performed to elucidate the independent values. OS was summarised using the Kaplan-Meier method with the log-rank test, and Cox proportional hazards models, adjusted for several independent clinical factors, were used to estimate mortality. Independent factors with a p value of <0.05 in the univariate analysis, or those considered clinically relevant, were included in the multivariate analysis; factors with a high correlation (>0.6) were excluded as covariate factors to avoid multicollinearity. All multivariate analyses were conducted after confirming the fitting of models. Statistical significance (p) was set at <0.05. All statistical calculations were performed using JMP PRO V.15.1.0 .Early-onset CTRCD was detected in 23 of the 136 patients (17%); symptomatic HF was observed in 11 of them, including three severe HF required ventilatory support. The median duration from HSCT to CTRCD diagnosis was 24 (9 to 35) days.The median age of the included patients was 51 (37 to 61) years at the time of HSCT, and there was no difference in age between the CTRCD and non-CTRCD groups . Creatin10.1136/openhrt-2022-002007.supp1Supplementary dataUnderlying diseases included acute myeloid (n=60), acute lymphoblastic leukaemia (n=21), chronic myeloid (n=2) and other types of leukaemia (n=15) as well as malignant lymphoma (n=35) and plasma cell neoplasm (n=3). Eighty-nine patients (65%) were categorised as non-CR at the time of HSCT. The sources of transplanted cells were bone marrow (n=58), cord blood (n=34) and peripheral blood (n=44) stem cells, including those from haploidentical donors (n=13). All recipients who underwent haploidentical peripheral blood stem cell transplantation had a non-CR status. The incidence of high-grade acute GVHD (grade III or IV) was significantly higher in the CTRCD group than in the non-CTRCD group .In all participants, LVEF decreased from 68% (63%–73%) to 63% (56%–72%) after HSCT (p<0.001). LVEF after HSCT was 41% (26%–50%) in patients with CTRCD and 66% (60%–73%) in those without CTRCD (p<0.0001) . LVEF re2; OR, 1.04; 95% CI 1.00 to 1.07; p=0.032) and the grade of acute GVHD  had a significant association with early-onset CTRCD  was found to be significant predictors of early-onset CTRCD in univariate analysis  . Remarkaet CTRCD . This reet CTRCD .The OS rate was significantly lower in recipients with early-onset CTRCD  than in those without early-onset CTRCD  months; p<0.001; Regarding the cause of death, primary disease and treatment-related deaths were observed in 39 (29%) and 42 (31%) patients, respectively . Early-oThis study elucidated the predictors and prognostic impact of early-onset CTRCD after allo-HSCT in patients with haematological malignancies, and two major findings were identified. First, severe acute GVHD, in addition to high-dose cumulative anthracycline, was a significant indicator of early-onset CTRCD. Second, patients with early-onset CTRCD had insufficient OS with a higher primary disease mortality than those without early-onset CTRCD.et alHertenstein Notably, grade of acute GVHD had a significant association with early-onset CTRCD. The graft versus host reaction was reported to have direct cardiotoxicity through donor T-cell infiltration into the myocardium as well as indirect toxicity due to cytokine release.2 has been demonstrated to increase the risk of HF by up to 10-fold.Our study also demonstrated an association between the cumulative dose of anthracycline and early-onset CTRCD. Several mechanisms of anthracycline-related cardiomyopathy have been suggested, such as oxidative stress, redox cycling by iron complexes and genetic variants.Early-onset CTRCD increased the risk of overall death by two-fold, and the HR for overall death was higher in patients with early-onset CTRCD than in those with a non-CR status. This suggests that early-onset cardiac dysfunction is a highly important determinant of recipient survival. As a cause of death, early-onset CTRCD has been shown to increase the risk of primary disease death more than double. One of the possible reasons for the high primary disease mortality in patients with CTRCD is the undertreatment of the primary disease. Treatment for refractory haematological malignancies after HSCT is performed with much difficulty due to decreased performance status, impaired immune system and tissue damage—including to the cardiovascular system—during prior treatment.Early detection and treatment of cardiac dysfunction are of great significance to avoid undertreatment of haematological malignancies caused by HF. Repeated examinations of biomarkers such as troponin and echocardiographic parameters including global longitudinal strain may be useful for early detection of cardiac injury.A recent study suggested that HF is induced or aggravated via inflammation provoked by somatic mutations associated with clonal haematopoiesis of indeterminate potential (CHIP), such as tet methylcytosine dioxygenase 2 (TET2) and deoxyribonucleic acid methyltransferase 3 alpha (DNMT3A).This study has some limitations. First, LVEF measured by the Teichholz method, which allows a potential off-axis measurement and has a relatively low accuracy of intra-LV volume presumption, was adopted. This is because LVEF from biplane image could not be measured in part of the recipients because of the difficulty in the apex approach in the lateral position due to poor physical status. Although CTRCD in this study was defined by only LVEF, detection of cardiac dysfunction by only LVEF poses a potential limitation as LVEF can be affected by volume status, preload and afterload. Subtle deterioration in LV systolic function may be better detected by the global longitudinal strain method.Our study identified severe acute GVHD as well as higher cumulative anthracycline as indicators of early-onset CTRCD. Additionally, early-onset CTRCD was an independent factor for poor prognoses with a higher primary disease mortality in recipients following allo-HSCT. Further research is needed to clarify the mechanism underlying the relationship between CTRCD and GVHD, an optimised regimen of less cardiotoxic cancer chemotherapy for patients with CTRCD and the appropriate time to initiate HF treatment in recipients of allo-HSCT.


Mage = 32.31, SDage = 12.40, 39.8% women) were recruited and completed an online survey. The results showed that participants with regular exercise scored lower than those without exercise on ADHD, impulsivity, and PPU . Using latent moderated structural equations (LMS), the findings revealed that the relationship between ADHD symptoms and PPU was mediated by impulsivity, and physical exercise moderated this relationship . Specifically, when individuals’ physical exercise was higher than 0.84 standard deviations above the mean, the positive predictive effect of impulsivity on PPU was not significant. These findings indicate the important role of impulsivity in the relationship between ADHD and PPU, and physical exercise could be a meaningful component of interventions among individuals experiencing PPU.Investigating the relationship between attention-deficit/hyperactivity disorder (ADHD) symptoms and impulsivity will benefit our understanding of the concept of problematic pornography use (PPU), and revealing predisposing and malleable moderators of PPU will be beneficial for its prevention and intervention. The current study not only aimed to observe these relationships, but also explored the potential moderating role of physical exercise in the general population. A total of 600 Chinese adults ( The availability of the internet has provided people with unprecedented access to sexually explicit materials ,2,3, eveImpulsivity is a multidimensional construct , referring to the tendency to act prematurely and without foresight, and is agreed to be a core symptom of attention-deficit/hyperactivity disorder (ADHD) ,20. TherAs impulsivity is a prominent manifestation of ADHD, several studies showed that individuals with ADHD demonstrated elevated levels of impulsivity as measured by a variety of tasks  and selfSince physical exercise is frequently used as a non-pharmacological complementary treatment recommendation for impulsivity-related psychopathologies ,34,35, pwww.wjx.cn (accessed on 2 December 2021)) in December 2021. The study was advertised as a research project about problematic pornography use, including impulsivity and ADHD symptoms. It took approximately 8 min to complete the survey. Participants were informed about the aims of the survey and would receive CNY 10 in compensation after completing it. Informed consent was obtained from the participants before data collection, and participants were assured of their anonymity. Eligible participants had to be 18 years old or older and had used pornography in the past six months. To prevent potential biases rooting in individual heterogeneity , SRMR = 0.07. The results showed that the main effect of impulsivity , ADHD  and gender  on PPU were statistically significant. All independent variables together accounted for 29.0% of the variance in PPU. As the model without the latent interaction fit the data well, we could proceed to Step 3.Following the assessment of the measurement model, an SEM without the latent interaction term (Model 2) was estimated. We only estimated the main effects of impulsivity, ADHD, and physical exercise on PPU. Model 2 had an acceptable fit to the data: χ2 (1) = 7.05, p < 0.01), and physical exercise significantly moderated the relationship between impulsivity and PPU . The estimated index of moderated mediation was −0.10, 95% CI  and the indirect effect of mediation was 0.22, 95% CI . All the independent variables accounted for 30.1% of the explained variance in PPU  was added to Model 3. To evaluate the model fit of this LMS model, we conducted a chi-square difference test based on the log likelihood values and scaling correction factors estimated from model 3  and model 2 . The results indicated that Model 3 showed a significant improvement in model fit  , with having a steeper slope in the case of low exercise. We also plotted the interaction effect with the Johnson–Neyman technique [To better understand the moderation effect, we conducted a simple slope test using bootstrapping to examine the statistical significance of the effect of impulsivity on PPU, with given conditional values of exercise habits ( ± 1 SD) . In bothechnique  providedechnique . Figure Exploring potential predisposing factors of PPU will contribute to better understanding its development and maintenance. Among these characteristics, ADHD and impulsivity were deemed important in prior studies, but no closer look was taken on these variables considering them concurrently. The present study not only revealed a positive and moderate association among ADHD, impulsivity and PPU, but also showed that impulsivity worked as a mediator in this association, that is, individuals with higher levels of ADHD may experience higher levels of impulsivity, which, in turn, may result in higher levels of PPU. Additionally, the predictive level of impulsivity on PPU depended on the individual’s amount of physical exercise. More precisely, for those individuals who exercised regularly, the predictive effect of impulsivity on PPU seemed to disappear. These results provide information for developing efficient and cost-effective intervention strategies for PPU.This study found a moderate and positive association between ADHD and PPU, which was slightly higher than in recent previous studies . As suggIn addition to the direct effect of ADHD symptoms on PPU, the mediation of impulsivity in the association between ADHD and PPU implied that impulsivity might be a possible mechanism explaining this association. The mediating role of impulsivity might root in the fact that urgency and sensation seeking (the two major dimensions of impulsivity) are common features of ADHD ,72, whicAccording to the notions of the I-PACE (Interaction of Person-Affect-Cognition-Execution) model, impulsivity was identified as an important predisposing factor of PPU ; howeverThere were some limitations in the present study that needed to be addressed. Because the data was collected using anonymous self-report measures, the reliability of the results is dependent on the respondents’ honesty and accuracy in understanding the scale items. Due to the use of self-reported scales without clinical diagnosis, only the associations of ADHD symptoms, impulsivity, and PPU could be examined without establishing comorbidity rates. Future studies may apply various research methods to assess not only the self-reported severity of ADHD symptoms, impulsivity, and PPU but also clinical diagnosis. Given that impulsivity is a multi-dimensional and multi-faceted construct and different dimensions may play different roles in PPU , more reImpulsivity did contribute as importantly and directly to PPU in this study as previous studies suggested. This result has conceptual and research implications: supporting that PPU is a sub-type of CSBD and that it is reasonable to be included under the classification of impulse control disorders in the ICD-11. In line with the results of previous studies, ADHD may contribute to individuals’ PPU ,25. ThusThe findings of the present study showed that impulsivity was a mediator between ADHD and PPU, physical exercise moderated the relationship between ADHD and PPU. Thus individuals with PPU should also be screened for ADHD in the diagnostic process and exercise might help individuals reducing their PPU.


At the intersection of injury-prone sports such as baseball and conditions like ADHD that affect all aspects of life, there is a lack of research. This limits the availability of preventive care programs designed to target potential risks and promote a safe experience. In this retrospective cohort study, we assess the frequency of injury in youth baseball players with and without ADHD, along with further investigation into how treatment with stimulant medication may modify risk factors. The data for this study were obtained in deidentified, aggregate format from the TriNetX research database. We identified all patients under 25 years of age with a designation of baseball activity. Within this population, we separated patients by presence or absence of ADHD diagnosis, and then by stimulant usage. The studied outcomes were injuries commonly occurring in baseball, including fractures, sprains, and specific injury patterns. We identified 17,710 patients under 25 years old with designated baseball activity, 1,183 of which had a diagnosis of ADHD. Of these, 511 had a history of stimulant medication and 470 had no history of stimulant use. For most events , there were no statistical differences between cohorts. The overall ADHD cohort significantly differed from the Not ADHD cohort in 3 events: “thorax, abdomen, pelvis injuries,” “ankle sprain,” and “concussion.” When athletes with ADHD received treatment, this trend reversed for select injuries: “any fracture”, “head or neck injuries”, “upper limb injuries”, and “lower limb injuries” were less likely in ADHD athletes on stimulants. Given the ongoing debate around stimulant use in athletics, our study is relevant to many patients, providers, and the baseball community. Attention-deficit/hyperactivity disorder (ADHD) is one of the most common childhood neurodevelopmental disorders, affecting 6%–9% of children and adolescents in the United States . It is cBaseball is a longstanding facet of American culture. In 2020 alone, 3,403,000 children between the ages of 6–12 and 1,845,000 youths aged 13–17 played baseball; numbers which were even higher before the COVID-19 epidemic  and has been well-established for medical research, including a wide range of fields such as obstetrics , sexualiUsing International Classification of Diseases (ICD) codes, we identified all patients under 25 years of age with a designation of baseball activity (Y93.64) between August 11, 2002 and August 11, 2022. Within this population, we separated patients by presence or absence of ADHD diagnosis (F90). The ADHD cohort was further separated by stimulant usage. Stimulant use was defined by the presence of either amphetamine-class medications or phenidate-class medications individually. Patients with both amphetamine- and phenidate-class medications present at the same instance in their chart were excluded from analysis, as combined stimulant use is reserved for significantly severe cases .Using the TriNetX software, we performed statistical analysis between the cohort without ADHD and each of the other groups, for a total of 3 analyses . Prior to comparison, the cohorts were balanced based on age, sex, and race using nearest-neighbor matching to a difference in propensity scores <0.1 . After mt-test was used to compare event rates between cohorts. Odds ratios with a 95% confidence interval were also calculated from event rates. The results are compiled in P < 0.05. As this study contained only deidentified aggregate data, the Colorado Multiple Institutional Review Board (COMIRB) designated it as non-human research not in need of approval.The studied outcomes were injuries commonly occurring in baseball: “upper limb fractures,” consisting of fractures of the shoulder, humerus, forearm, wrist, or hand ; “lower limb fractures,” consisting of fractures of the femur, lower leg, ankle, or foot ; “any fractures,” consisting of any prior mentioned fracture type; “head & neck injuries” consisting of injuries to the musculoskeletal system above the clavicle (ICD: S00–19); “upper limb injuries” consisting of injuries from the shoulder to fingers (ICD: S40–69); “lower limb injuries” consisting of injuries from the hip to toes (ICD: S70–99); “thorax, abdomen, pelvis injuries” consisting of injuries from the clavicle to the hip, including the innominate and genitals (ICD: S40–69); shoulder sprain (ICD: S43.4); rotator cuff and/or labrum injury ; elbow sprain (ICD: S53.4); ulnar collateral ligament (UCL) damage (IDC: S53.44 & S53.3); knee sprain (ICD: S83.4–5); ankle sprain (S93.4); and concussion (ICD: S06.0). Injuries were considered binary variables based on presence or absence of the corresponding ICD code in the health record within the time window. A P = 0.001), “ankle sprain” , and “concussion” . The no stimulant group differed in “ankle sprain” , and “concussion” . The stimulant group differed in 4 of the 14 measured outcomes but not in the 3 outcomes mentioned previously by other groups. Further results are in We identified 17,710 patients under 25 years old with designated baseball activity, 1,183 of which had a diagnosis of ADHD. Of these, 511 had a history of stimulant medication and 470 had no history of stimulant use. For most events , there were no statistical differences between cohorts. The overall ADHD cohort significantly differed from the Not ADHD cohort in 3 events: “thorax, abdomen, pelvis injuries” , which most often occurs in high-energy collisions , but theConcussion is an important event that is increased in both overall ADHD and ADHD without stimulant use. Research into associations between concussion and athletes with ADHD has been performed at all levels of baseball, including high school, college, and professional play. In one study, more than 50% of athletes with ADHD in NCAA Division I sports reported at least one prior concussion, compared to 14% of athletes without ADHD . Given tConcussions were not the only improved outcome present in our stimulant group. Compared to baseball players without ADHD, athletes with ADHD on stimulants were less likely to have fractures of the axial skeleton, less likely to have any fractures at all, and less likely to injure the head, neck, upper limb, and lower limb. Reduced fracture rates in ADHD patients on stimulants has been reported in prior research , but theStimulant use is a controversial topic within the baseball community . StimulaAs the average age in our study is 17.7 years old, our findings are more relevant for athletes at the high school and early collegiate level. Stimulants are the mainstay of ADHD treatment due to their highly beneficial effects on academic performance, as well as social development, emotional regulation, and overall mental health , 24. StiWhile our study avoids many potential confounders, such as age, sex, and race, there are some limitations that restrict the generalizability of our findings. The data obtained from TriNetX are deidentified and presented in aggregate form, which prevents analysis on an individual level and restricts important information such as severity of ADHD symptoms. Furthermore, electronic medical records are limited to information entered by health care providers; it is extremely likely that our findings are an underestimate of baseball injuries as we only included patients identified as playing baseball through their health record. Similarly, medications may be entered in the record but not taken. However, the large size of our study mitigates most of these limitations, and ensures our findings have some generalizability to ADHD athletes in baseball.Given the growing population of ADHD youth, and the ongoing debate around stimulant use in athletics, our study is relevant to a wide variety of patients, providers, and the baseball community at large. Still, further research is needed to investigate potential causes behind the associations identified. As more is discovered about the link between ADHD and injuries, the use of stimulants in baseball should be continually reassessed. With collaborative effort, the rate of injuries in ADHD athletes might be reduced, allowing more players to continue enjoying the quintessential American pastime.


Numerous resting-state studies on attention deficit hyperactivity disorder (ADHD) have reported aberrant functional connectivity (FC) between the default-mode network (DMN) and the ventral attention/salience network (VA/SN). This finding has commonly been interpreted as an index of poorer DMN regulation associated with symptoms of mind wandering in ADHD literature. However, a competing perspective suggests that dysfunctional organization of the DMN and VA/SN may additionally index increased sensitivity to the external environment. The goal of the current study was to test this latter perspective in relation to auditory distraction by investigating whether ADHD-adults exhibit aberrant FC between DMN, VA/SN, and auditory networks.n = 17) and controls (n = 17); from which the FC between predefined regions comprising the DMN, VA/SN, and auditory networks were analyzed.Twelve minutes of resting-state fMRI data was collected from two adult groups: ADHD (A weaker anticorrelation between the VA/SN and DMN was observed in ADHD. DMN and VA/SN hubs also exhibited aberrant FC with the auditory network in ADHD. Additionally, participants who displayed a stronger anticorrelation between the VA/SN and auditory network at rest, also performed better on a cognitively demanding behavioral task that involved ignoring a distracting auditory stimulus.Results are consistent with the hypothesis that auditory distraction in ADHD is linked to aberrant interactions between DMN, VA/SN, and auditory systems. Our findings support models that implicate dysfunctional organization of the DMN and VA/SN in the disorder and encourage more research into sensory interactions with these major networks. Current etiological models of attention deficit hyperactivity disorder (ADHD) emphasize dysfunctional interactions between intrinsic brain networks, rather than regional brain abnormalities, for explanations of behavioral and clinical symptoms in the disorder , ADHD participants showed significantly poorer attenuation in auditory regions. Further, this heightened auditory activity was correlated with individual differences in symptomatic inattentiveness and 2-bT performance—for which the ADHD group were significantly inferior to controls. In the current study, we pose the question as to whether these aforementioned outcomes are related to both individual, and group level variances in intrinsic FC between the DMN, VA/SN, and auditory regions.Heightened sensory sensitivity is a frequently reported symptom in adults with ADHD particularly in the auditory modality . HoweverOur first objective (O1) in this regard was to determine if a weakener DMN–VA/SN anticorrelation was evident in the ADHD group. Our second objective (O2) was to test for group differences in FC between auditory seeds  and regiM = 28, SD = 6.8) and 17 healthy controls . Of the 17 ADHD participants, 15 were prescribed stimulant medication and abstained from their medication for at least 48 h prior to testing. The 18-item adult ADHD self-report scale (ASRS) v.1.1 (The resting-state data for this study was obtained from the sample of participants from S) v.1.1  was usedImmediately prior to the task-based scan published in Participants were instructed to lie as still as possible, let their mind’s wander, and not to fall asleep. In order to make the acoustic environment as quiet as possible, the external auditory meatus of each ear was first protected with a self-hardening, moldable wax; next, participants were fitted with active noise canceling headphones  which further attenuated the background EPI gradient noise to ∼58 dB SPL. The headphones were kept in place via inflatable positioning pads  that also worked to minimize head movements within the 64-channel head coil.1 and included an additional denoising procedure in order to remove confounds of physiological noise , head movement, outlier scans, as well as constant, and first-order linear session effects. We applied the software’s default preprocessing pipeline for volume-based analyses but with indirect normalization to standard stereotactic (MNI) space as we had obtained gradient field maps during image acquisition  were entered into an ordinary least squares regression in order to remove confounding effects on the estimated BOLD signal in each voxel per subject and run. The covariates included five noise components from cerebral white matter; five noise components from cerebrospinal areas; 12 subject motion components , outlier scans identified in the preprocessing procedure and components representing the effect of each task-condition convolved with the canonical hemodynamic response function in order to reduce the influence of slow trends, initial magnetization transients as well as constant task-related effects.Temporal band pass filtering  on the BOLD signal was applied in order to minimize the influence of physiological head motion and other noise sources.M = 0.08, SD = 0.02; ADHD: M = 0.10, SD = 0.03) was not significantly different between groups, F = 3.8, p = 0.06; nor was the mean number of valid  scans  significantly different between groups F = 0.5, p = 0.49.Subsequent quality control analysis of preprocessing outcomes indicated that the mean framewise displacement (disregarding outlier scans) associated with micro-head movements  cluster-level threshold of p < 0.05. Eventual post hoc, ROI-level exploration of the hypothesized reduced anticorrelation (ADHD > Controls) between the two networks utilized an uncorrected, one-tailed p < 0.05 connection-level threshold. In addition, for each network, an FDR corrected (p < 0.05) ROI-to-ROI, 2-tailed univariate analysis  analysis  was usedanalysis  was usedp < 0.05. We additionally performed an FDR corrected (p < 0.05) ROI-to-ROI, 2-tailed univariate analysis . To this end, a separate one-way MANOVA for each target ROI  was used to determine the significance of the TFCE scores. Eventual post hoc analysis utilized an uncorrected, two-tailed p < 0.05 connection-level threshold to identify the individual within-cluster ROI-to-ROI connections associated with the brain-behavior relationship. 2b-T data was missing for one of the ADHD participants, so this TFCE analysis included only 16 of the 17 ADHD participants. Similarly, impulsivity scores were missing for one of the control participants so TFCE analysis of the relationship between FC and impulsivity as well as total ASRS scores included only 16 of the 17 control participants.To explore the brain-behavior relationship between individual differences (collapsed across groups) in connectivity and 2b-T accuracy and ADHD-symptom severity (O3), a threshold free cluster enhancement (TFCE) procedure  was usedF = 7.2, p-FDR = 0.008, in ADHD than controls (O1). Post hoc analysis of ROI-to-ROI connections indicated that the weaker anticorrelation (p-uncorrected) was most strongly associated with the medial prefrontal cortex (PFC) of the DMN and was evident across all VA/SN regions  with individual differences (collapsed across groups) in ADHD-symptom severity. Results indicated that the weaker anticorrelated DMN–VA/SN FC was mostly associated with the severity of inattentive and combined symptoms across participants  = 4.7, p-FDR = 0.006; and significantly less anticorrelated with the medial PFC of the DMN F = 4.8, p-FDR = 0.006, in the ADHD group; providing support to the hypothesis that adults with ADHD may be more inherently sensitive to their acoustic environment (O2). No differences between groups were observed for any of the other target ROIs. Nor did we observe groups differences in FC between auditory regions alone.Between-group, seed-based analysis indicated that the phasic resting-state activity in auditory regions was significantly more positively correlated with the right supramarginal gyrus (SMG) of the VA/SN, p-FWE = 0.040. Post hoc connection-level analysis , identified a significant cluster of connections between auditory and VA/SN ROIs that were negatively associated with 2b-T accuracy. TFCE = 34.9, ysis see . Taken tysis see . Clustere scores  and one y scores  wherein The purpose of the current study was to explore whether adults with ADHD would show aberrant FC compared to healthy controls between DMN, VA/SN, and auditory regions. Our combined results were rather striking. First, as per expectations, a weaker anticorrelation between the VA/SN and DMN was observed in ADHD participants. Second, this aberrant connectivity was underscored by an enhanced coupling between auditory ROIs and the right SMG of the VA/SN and a reduced anticorrelation between the medial PFC of the DMN and auditory ROIs. Third, it was shown that participants who displayed strong intrinsic segregation of the VA/SN and auditory ROIs at rest, were also better at performing well on a cognitively demanding visual working memory task that concurrently required participants to ignore a streaming acoustic signal. We discuss these results in more detail over the proceeding subsections.n = 80) of adults with ADHD. However, unlike some reports from previous studies in ADHD  that concurrently required participants to ignore a streaming acoustic signal (∼75 dB SPL). Throughout this task, controls were more proficient than ADHD participants at attenuating the evoked auditory activity from the distracting acoustic signal and performed overall better than ADHD participants. In addition, the more attenuated the auditory evoked responses were across participants, the lower their symptom severity scores of inattentiveness. In the current study, we showed that participants who had the capacity to perform well on the 2b-T whilst ignoring the distracting acoustic signal, also tended to have more intrinsically segregated VA/SN–auditory connectivity at rest. This pattern of VA/SN–auditory FC was also shown to have an inverse relationship with ADHD-symptom severity. Specifically, increased connectivity between the right SMG of the VA/SN and auditory cortices  was positively associated with the severity of ADHD-symptoms across participants. In sum, the resting-state brain-behavior relationships observed in the current study are supportive of theories that suggest that the VA/SN plays a pivotal role in the manifestation of attentional deficits in neuropsychiatric disorders , whereinBecause we have already addressed in detail the limitations regarding our sample in In addition to the aforementioned limitations regarding our sample, two methodological limitations specific to this study are worthy of addressing. First, we did not implement any physiological methods that would allow us to monitor the arousal levels of the participants throughout the resting-state period. The functional resting-state duration was ∼12 min—prior to which participants also underwent ∼6 min of anatomical scans—and it is known that some participants can fall asleep in the scanner under conditions where they are left to rely on mentation as their sole source of stimulation. We can however, state that only two accepted applicants for this study reported falling asleep in the scanner (one ADHD and one control), and these participants were thereby excluded from the sample used here and in REST (VILA in Swedish), which slowly moved (figure-eight animation) within participants’ field of view. This animation continued throughout the duration of the resting-state period. Had participants opted to open their eyes during the resting-state scan, then this was the only visual stimulation they received. Compared with a visually salient fixation cross—which many studies use under these circumstances—we tentatively suggest that our choice of visual stimulation, albeit novel, may have at least circumvented unwanted externally-directed frontal eye field activity associated with ocular fixation  reading: fixation , even thfixation . HoweverIn accord with previous studies, a reduced resting-state anticorrelation between the VA/SN and DMN was observed in our sample of adults with ADHD. Moreover, core hubs of the DMN and VA/SN, which respectively have been implicated in top-down and bottom-up regulation of attention to sensory events, exhibited aberrant FC with the auditory network in ADHD participants. Additionally, it was shown that participants who displayed stronger intrinsic segregation of the VA/SN and auditory network at rest, were also better at performing well on a cognitively demanding visual working memory task whilst attenuating distracting auditory stimulation (task conditions where ADHD participants proved inferior to controls). Overall, our collective results are consistent with the hypothesis that auditory distraction and more generally inattentiveness in ADHD is linked to aberrant interactions between DMN, VA/SN, and auditory systems. Importantly, our findings contribute further evidence to current etiological models of ADHD that implicate dysfunctional organization of DMN, VA/SN and other major intrinsic networks in behavioral and clinical symptoms in the disorder. Our findings also encourage more research into sensory interactions with these major intrinsic networks so that we can refine our theories of inattention and better understand factors that impact symptoms of sensory distraction in the disorder.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Regional Ethical Review Board in Linköping, Sweden (DNR 2019-06158). The patients/participants provided their written informed consent to participate in this study.JR, RB, AC, and HD contributed to the conception and design of the study. AC and RB were responsible for participant recruitment and data collection. RB was responsible for data analysis as well as manuscript drafting and was assisted by IP, AC, and CS. All authors scrutinized the statistical analysis, contributed to the manuscript’s revision, and approved submitted version.


Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder characterized by inattention and/or hyperactivity-impulsivity resulting from the interaction of genetic and environmental risk factors. Family studies shows that persistent ADHD is very familial.We aim to review the literature on this condition and its heritability and describe the implications that a possible misdiagnosis can have during life.Bibliography review was performed using the databases PubMed and Cochrane, using the following keywords: “ADHD”; “Adults”; “Heretability”; “Family” and “Rater effect”.Childhood ADHD persists into adolescence and adulthood substantially, identified in some studies, as going up to 78%. The prevalence of ADHD in children and adults is between 2.5% and 5% worldwide. Family studies have shown that children of adults with ADHD are at higher risk of having ADHD. Some large-scale twin studies of adult ADHD, used self-report assessments of ADHD symptoms and estimated the heritability of this condition to be between 30 to 40%, which differs from other studies that analyse parents and teachers responses and estimates heritability to be between 60 and 90%.Since there is a direct influence of the evaluators in estimating the extent of ADHD heritability, future studies need to clarify and describe in detail all the related characteristics of the raters. Although ADHD is widely studied, there is still a lot to learn about its etiology. The diagnosis of ADHD is clinical and complex and must be considered both in childhood and adolescence and in adulthood, with special emphasis on the family antecedents.No significant relationships.


The link between Attention-Deficit/Hyperactivity Disorder (ADHD) and steeper delay discounting has been established and incorporated into theories of ADHD. This study examines a novel interpretation according to which ADHD is linked to sub-optimal temporal decision-making and suggests inconsistency as a potential underlying mechanism. In two experiments, MTurk workers completed a self-report questionnaire on symptoms of ADHD and a temporal decision making task consisting of choices between smaller–immediate and larger–delayed options. The delayed option was better in some items, whereas the immediate option was better in others. The rate of choices of the delayed option and the consistency of choices were measured. The results of both studies show that high symptoms of ADHD were linked to fewer choices of the delayed option when it was better, but also to more choices of the delayed option when it was not better. In addition, ADHD was linked to higher inconsistency in both conditions. The findings suggest that ADHD is linked to sub-optimal temporal decision-making rather than steeper delay discounting, and provide further support to the phenomenon of inconsistency in ADHD. Attention-Deficit/Hyperactivity Disorder (ADHD) is a neuro-developmental condition defined by persistent symptoms of inattention and/or hyperactivity–impulsivity interfering with functioning or development . ADHD isk  that is computed from the participant’s pattern of choice in a monetary choice questionnaire [Time-related decisions are traditionally characterized by the term delay discounting, meaning that a future payoff has a lower utility than an equivalent payoff in the present. The research on this topic is vast; however, it is mostly agreed that delay discounting is subjective and can be determined experimentally . For exionnaire .Research on temporal decisions often includes a temporal discounting task: the participant is asked to choose between two monetary rewards, a small and immediate or a larger but delayed ,14. As mk parameter for this problem  is around 0.00003, which is very low, so an individual’s k value needs to be at this level or lower for them to accept such an offer. Despite such examples, studies of time preferences of people with ADHD have implicitly assumed that the delayed reward is the better choice. In other words, optimality and delay have been confounded, which raises the question of whether this confounding might have led to overlooking alternative explanations for the immediacy tendency among people with ADHD.While the evidence for immediacy bias seems clear, the studies documenting this tendency have focused on cases where the delayed reward option is better than the immediate one. This focus is well justified and characterizes many real-life temporal dilemmas. However, there might be situations in which it is better to choose the immediate payoff, or at least most people would agree. For an obvious example, consider many banks saving accounts that currently offer incredibly low interest rates. Most people would agree that investing USD 1000 in an account with a yearly interest of 0.01% is not worthwhile or profitable. The calculated An alternative explanation to the temporal decision-making deficit in ADHD is a sub-optimal valuation of delay. This novel interpretation states that ADHD might be related to sub-optimal choices regardless of immediacy. Specifically, when the delayed option is better, people with ADHD might indeed lean towards the immediate option. Still, when the immediate option offers the better choice, people with ADHD might lean towards the less attractive delayed option. This latter tendency, if it exists, contradicts the previously mentioned conclusions regarding steeper delay discounting. Specifically, if ADHD is linked with immediacy preference, people with ADHD should have an advantage in immediate-is-better situations. The first goal of this research is to compare these distinct interpretations.The current study’s second goal is to explore choice inconsistency as a possible explanation for temporal decision-making in ADHD. The consistency of preferences is a core element for making optimal decisions , and incThe current paper examined the sub-optimal valuation and inconsistency hypotheses using two studies. In Experiment 1, we used a between-subject design to explore the hypotheses that people with a high level of symptoms of ADHD will show sub-optimal decision-making in both “better–delayed” and “better–immediate” conditions. Experiment 2 used a within-subject design, where the same participants chose between two options under both better–delayed and better–immediate conditions.The sample consisted of 200 Amazon Mechanical Turk workers  with a “Master” qualification (workers with high credibility). The participants received a compensation of USD 0.8 for their participation. After giving their informed consent, participants were randomly assigned to the study task conditions. All studies reported here were approved by the Ethics Committee of the Seymour Fox School of Education, The Hebrew University of Jerusalem.k) corresponding to indifference between the two rewards. The original scale was split, and items were added to create two scales of 27 items, one with low k values (0.00016–0.0025) and one with high k values (0.045–0.35), to create the two conditions “better–immediate” and “better–delayed”. The items were presented in a fixed order to ensure that the k values were mixed properly  based on Kirby et al.’s  scale asy et al. ).The Adult ADHD Self Report Scale (ASRS-V1.1) , adaptedAttention check questions. To verify that the participants attended to the content of the task, two questions were added: in the middle of the MCQ task, the participants were asked to choose the immediate option , and in the middle of the ASRS questionnaire, to select “often” .In addition, participants reported demographic information  and ADHD-related information (ADHD medication on the day of the experiment and a history of ADHD diagnosis).In total, 2 participants who failed the attention check and 23 who completed the whole study in less than four minutes were excluded from further analysis . The latter criterion was applied to improve data quality, which was found to be poorer when “speeders” were included in online samples . The fink values of the questionnaire [k value of the 24th item. However, suppose a participant mainly chose the immediate option and only chose the delayed option at the 6th, 8th, 10th, 25th, and 26th items. In that case, their assigned k value will be identical to the previous participant, but with a consistency score of 85%. The discounting rate was operationalized as the percent of times a participant chose the delayed reward. The variables age, gender, socioeconomic position, and education were controlled. Regression analyses were performed to examine the relationship between ADHD, delay discounting, and optimality. Considering previous findings of the relationship between delay discounting and psychiatric variables [The consistency score was calculated by ordering the items and computing the percentage of choices most consistent with an indifference point at one of the different ionnaire . For exaariables , we examExperiment 2 was conducted to evaluate the robustness of Experiment 1′s findings using a within-subject design. The same participants chose between two options under both better–delayed and better–immediate conditions, enabling us to examine whether the same participants made sub-optimal choices under both conditions.Mdn = 25–34); 31% female) were recruited the same way as described in Experiment 1. The participants were instructed to choose the option they preferred in each of the 27 choice problems presented. The data of 14 participants were removed from the analysis due to response times shorter than four minutes.One hundred participants  based on Kirby et al.’s  scale watems see  was presk levels of the 27 choices as the within-subjects variable. The ASRS score and ASRS squared score were continuous covariates. A second analysis used consistency score as the within-subjects variable. Demographics and clinical information of the participants are presented in Data analysis. The questionnaires and the task were coded the same way as in Experiment 1. A repeated-measures ANOVA was used with low, medium, and high F  = 30.10, p < 0.001, R2 = 0.25), explaining 25% of the variance in delayed choices. The results reveal that people with higher ASRS scores chose more immediate rewards than those with lower scores ). The quadratic model had better fit  = 19.60, p < 0.001, R2 = 0.30), showing that the level of delayed choices increased and then (more steeply) dropped with the increase in ASRS scores ). In the better–immediate condition, the linear model was insignificant  = 0.57, p = 0.452, R2 = 0.08), while the quadratic model was significant  = 4.32, p = 0.017, R2 = 0.10), explaining 10% of the variance in delayed choices. It showed that ASRS significantly predicted delayed choices in an opposite pattern from the “better–delayed” condition ). That is, the pattern of the quadratic model shows that the level of delayed choices decreased and then increased with the rise in ASRS score. The quadratic curves in both conditions are depicted in Regression analyses were used to examine linear and curvilinear relations between the level of symptoms of ADHD and sub-optimal temporal decision-making. Separate analyses were performed for the two conditions (“better–delayed” and “better–immediate”). In the better–delayed condition, the linear model was significant  = 51.59, p < 0.001), explaining 36% of the change in delayed choices (R2 = 0.36). The quadratic model improved the prediction to 44%  = 35.38, p < 0.001, R2 = 0.44). In the better–immediate condition, the linear model was also significant  = 39.11, p < 0.001), explaining 33% of the change in delayed choices (R2= 0.33). The quadratic model improved the prediction to 43%  = 29.74, p < 0.001, R2 = 0.43). In both conditions, a higher ASRS score significantly predicted less consistency in choices ; β = −0.57, p < 0.001, 95% CI ; respectively). According to the quadratic model, the level of consistency somewhat increased and then (more steeply) dropped with the rise in ASRS scores, in both conditions ; β = −1.76, p < 0.001, 95% CI ; respectively).We next examined whether the level of ADHD affects choice consistency. Specifically, we regressed the rate of consistent choices on the ASRS score under each of the two aforementioned regression models  as the dependent variables, and the ASRS score and ASRS squared score as continuous covariates, to examine the hypothesis of sub-optimal decision-making in relation to high levels of symptoms of ADHD. The analysis yielded a significant interaction effect between both covariates and delayed choices  = 6.43, p = 0.003, F  = 10.11, p < 0.001, F  = 0.67, p = 0.52).We conducted a repeated-measures ANOVA with the three levels of k levels  = 27.47, p < 0.001, R2 = 0.25), explaining 25% of the variance in delayed choices. ASRS significantly predicted less delayed choices ). The quadratic model improved the prediction to 30%  = 17.97, p < 0.001, R2 = 0.30), which implies a rise in choices of the delayed reward that dropped with the rise in ASRS score ). When the k level was low, and it was better to choose the immediate reward, the linear model was insignificant  = 0.31, p = 0.580). However, the quadratic model was significant and explained 10% of the variance  = 4.78, p = 0.011, R2 = 0.10), according to which there was a decrease in the delay options chosen and then a rise compliant with the rise in ASRS score ). For the middle items, the results were similar to those of the high-level delay items.To explore the delay × ASRS interaction, we performed separate post hoc regression tests for the three k levels a. When tk levels  as the dependent variable. The analysis yielded a significant main effect for ASRS and the quadratic covariate ASRS squared  = 13.75, p < 0.001, F  = 33.10, p < 0.001, p’s > 0.05).To test the hypothesis of inconsistency related to a high level of symptoms of ADHD, we performed a second repeated measures ANOVA with consistency scores of the previous y levels b. InteraThe results show that participants with a high level of ADHD symptoms demonstrated sub-optimal choices both when the better choice was the immediate one and when it was the delayed one. In other words, the same person with a high level of ADHD symptoms was more likely to choose both the immediate option when the delayed was better and the delayed option when the immediate was better. Further, high ADHD was related to less consistency in both contexts. The results support the claim that ADHD is characterized by sub-optimal and inconsistent temporal decision-making rather than steeper delay discounting and an immediacy bias.Previous studies have suggested that people with ADHD are characterized by a higher immediacy bias than controls in their temporal decisions ,7. Yet tTwo experiments were conducted to confront these competing hypotheses. The first compared a delay discounting paradigm where the delayed option was better with a condition where the immediate option was better. The second experiment tested whether the results of the first experiment were replicated at the individual level using a within-subject design. The results support the hypothesis that a high level of ADHD symptoms is related to sub-optimality in the valuation of the delay, rather than steeper delay discounting. This pattern implies that a person with ADHD might appear either impatient when the delayed reward is better or too patient when the immediate is better.Sub-optimal decision-making in people with ADHD was also evident in research on decision-making under risk. Dekkers et al.  conductek value is relatively high), typically, the discounting rate of the participant would be relatively consistent across trials, resulting in choosing the better option for most trials. A participant with a high level of ADHD would have a similar discounting rate on average. However, due to inconsistency, in some trials, the discounting rate would be lower than that of the participant with low ADHD, resulting in choosing the immediate option. Nevertheless, in other trials, the discounting rate of the participant with high ADHD would be higher than that of the participant with low ADHD, resulting in more choices of the delayed reward, which is the worse option in this example. As such, this inconsistency can account for sub-optimal choices, regardless of their direction.The second aim of this study was to explore inconsistency as a possible explanation for sub-optimal decision-making in ADHD. How can inconsistency explain the sub-optimal decisions of people with ADHD? For an example of a temporal discounting decision, the choice of whether to wait is determined by the discounting rate assigned to the delayed reward. For example, when facing a series of trials in which the immediate option is better . Importantly, our findings could hence be attributed to the advanced age of some of our participants, and the related neurological diseases and deficits. However, re-examining the data with age as a covariate did not have an impact on the results. We further made sure that participants did not report taking any medication for the treatment of neurological diseases. Future studies should take that issue into account in advance.Third, this study explored delay discounting using an experimental task. The use of the present and similar tasks to examine delay discounting is accepted and well-spread ,7,8. Yetp < 0.001). Therefore, it seems that employing the exclusion criterion removed many of our high-ADHD participants, preventing the replication of some of the findings. Importantly, this demonstration suggests that consistency, or inconsistency, is a fundamental mechanism of ADHD. It also indicates that inconsistency appears together with steeper delay discounting when the delayed option is optimal. However, when the immediate option is optimal, a high inconsistency that characterizes the far end of the ADHD symptoms continuum may be the source of the effects we reported in the results section above.Fourth, some authors recommended excluding responses with consistency scores lower than 0.8 in the MCQ paradigm . Here, wLastly, the suggested mechanism of inconsistency is not the only plausible explanation. In fact, it has been suggested that the sub-optimal decision-making of people with ADHD can be caused by the use of less complex strategies . FurtherFurther research should also investigate sub-optimality in the decision-making process of people with ADHD from a developmental perspective , with clIn conclusion, the current study’s findings suggest that ADHD symptoms might not be linked to steeper delay discounting, but rather to a sub-optimal valuation of the delay, leading to either impatient or overly patient sub-optimal choices. Importantly, ADHD is linked to general inconsistency, which can account for the sub-optimal decision-making deficit demonstrated in this study. Further research should investigate sub-optimality in the decision-making of people with ADHD, and inconsistency as a mechanism.


MesPDPPh)UO2(THF)and (Cl2PhPDPPh)UO2(THF), are reportedas the UVI uranyl adducts of the bulky aryl substitutedpincers (MesPDPPh)2– and (Cl2PhPDPPh)2– -3-phenyl-1H-pyrrol-2-yl)pyridine , and 2,6-bis-3-phenyl-1H-pyrrol-2-yl)pyridine , respectively).Following the in situ deprotonation of the proligand with lithiumhexamethyldisilazide to generate the corresponding dilithium salts, salt metathesis with [UO2Cl2(THF)2]2 afforded both compounds in moderate yields.The characterization of each species has been undertaken by a combinationof solid- and solution-state methods, including combustion analysis,infrared, electronic absorption, and NMR spectroscopies. In both complexes,single-crystal X-ray diffraction has revealed a distorted octahedralgeometry in the solid state, enforced by the bite angle of the rigidmeridional (ArPDPPh)2– pincerligand. The electrochemical analysis of both compounds by cyclic voltammetryin tetrahydrofuran (THF) reveals rich redox profiles, including eventsassigned as UVI/UV redox couples. A time-dependentdensity functional theory study has been performed on (MesPDPPh)UO2(THF) and provides insight into thenature of the transitions that comprise its electronic absorptionspectrum.The first actinidecomplexes of the pyridine dipyrrolide (PDP)ligand class, ( The synthesis of two uranyladducts of the pyridine dipyrrolideligand class is reported. The characterization of these complexesby cyclic voltammetry and electronic absorption spectroscopy revealsintriguing electronic profiles. With this in mind, researchers have leveragedPDP metal complexes in catalysis,50 atomand group transfer,61 and photochemistry.68 Despite this expanding wealth of research, PDP compounds of eitherlanthanide or actinide elements have not been reported.74Of late, a new family of tridentate pincer ligands,so called pyridinedipyrrolides (PDPs) in their dianionic, doubly deprotonated form (PDPArPDPPh)2– (Ar = Mes or Cl2Ph), (MesPDPPh)2– and(Cl2PhPDPPh)2–, derived fromthe double deprotonation of 2,6-bis-3-phenyl-1H-pyrrol-2-yl)pyridine  and 2,6-bis-3-phenyl-1H-pyrrol-2-yl)pyridine, may support compounds of the general formula(ArPDPPh)UO2(L) . These ligand precursors were attractive choices, aseach may be synthesized in a modular fashion on gram scales withoutthe need for chromatographic separations. Additionally, the rigidcoordination environments imparted by these ligand platforms wereanticipated to yield well-defined, symmetric compounds amenable tostraightforward study by solution NMR spectroscopy. Interestingly,despite the steric similarities of these compounds, the coordinationchemistry of this pair of ligands has been observed to have cleardifferences. For example, some of us have recently reported that the(Cl2PhPDPPh)2– ligand engagesin weak chloride-to-iron interactions in the solid state in iron compoundsin both the +II and +IV formal oxidation states.62Accordingly, our research groups haveendeavored to initiate thestudy of actinide-PDP compounds with the aim of establishing the fundamentalcoordination chemistry of these systems by utilizing the diamagnetic,largely inert, uranyl moiety as a convenient entry point. Interestedin the synthesis of uranyl compounds as a means to gain entry to actinidePDP chemistry, we anticipated that the previously reported bulky ligands(MesPDPPh)UO2(THF) and (Cl2PhPDPPh)UO2(THF) . These effortshave demonstrated that tridentate (ArPDPPh)2– ligands support rigid six-coordinate, distorted octahedraluranyl complexes both in the solid and solution state. CV studiesdemonstrate rich electrochemistry for both compounds, suggesting thatthe charged analogues may be chemically accessible. A complementarytime-dependent density functional theory (TD-DFT) study has been conductedas a means of further elucidating the nature of the electronic transitionsfor (MesPDPPh)UO2(THF). These calculationshave revealed that the nature of the dominant transitions in the visibleregion of the electronic absorption spectrum are primarily a resultof intraligand charge transfer (ILCT) with some ligand-to-metal chargetransfer (LMCT) contributions. We anticipate that the results presentedhere will serve as a foundation for future exploration in PDP f-elementchemistry.Herein, we describe a two-step, one-pot metalationprotocol forthe synthesis of a series of PDP uranyl complexes, namely (UO2(THF) 1. These 6D6) or CaH2 (CD2Cl2) after three freeze–pump–thaw cycles, and stored inthe glovebox over activated 3 Å molecular sieves. Uranyl chloridetrihydrate was purchased from International Bio-Analytical Industriesand used as received. All the remaining chemicals were purchased fromcommercial sources  andused without further purification. H2MesPDPPh,60 H2Cl2PhPDPPh,62 and [UO2Cl2(THF)2]275 were synthesized following reported procedures.All air- and moisture-sensitivemanipulations were carried out using a standard high vacuum line,Schlenk, or cannula techniques or in an MBraun inert atmosphere dryboxcontaining an atmosphere of purified dinitrogen. All solids were driedunder a high vacuum in order to be brought into the glovebox. Solventsfor air- and moisture-sensitive manipulations were dried and deoxygenatedusing a Glass Contour Solvent Purification System  and stored over activated 4 Å molecular sieves (Fisher Scientific)prior to use. Deuterated solvents for NMR spectroscopy were purchasedfrom Cambridge Isotope Laboratories, distilled from sodium metal (C238U) is a weak α-emitter (4.197 MeV) witha half-life of 4.47 × 109 years; manipulations andreactions should be carried out in monitored fume hoods or in an inertatmosphere drybox in a radiation laboratory equipped with α-and β-counting equipment.Caution! Depleted uranium  and 3 mL of diethyl ether, affordinga yellow suspension. In a separate vial, lithium hexamethyldisilazide was dissolved in approximately3 mL of diethyl ether. The LiHMDS solution was added dropwise to thesuspension of H2MesPDPPh with vigorousstirring, inducing an immediate color change to a brilliant yellow.Within minutes, complete dissolution of all the solids was observed;stirring was continued for approximately 2 h. In a separate vial,[UO2Cl2(THF)2]2  was suspended in 3 mL of diethyl ether andadded dropwise to the solution of Li2MesPDPPh, inducing an immediate color change to dark-red/brown. Themixture was stirred for 12 h, after which the suspension was filteredover a 1″ pad of Celite in a glass pipette plugged with a microfiberglass filter. A brown powder was collected on the Celite column andwashed three times with 2 mL aliquots of pentane. The material wasthen extracted from the Celite plug using 10 mL of dichloromethane(DCM). The red/brown extracts were collected in a tared, 20 mL scintillationvial and volatiles were removed in vacuo. The residue was then extractedinto benzene and passed through an additional Celite plug, collectedin a tared, 20 mL scintillation vial, and reduced to dryness. Theresulting dark residue was triturated with pentane, leaving a brick-redpowder that was identified as the title compound. Yield: 0.209 g,0.223 mmol, 53%. 1H NMR : δ 7.83 , 7.57 , 7.29 , 7.18–7.14 , 6.76 , 6.52 ,3.84–3.59 , 2.39 , 2.14 , 1.41–1.38 . 13C NMR : δ20.99, 21.21, 26.27, 76.88, 114.03, 114.35, 126.58, 128.63, 128.70,130.66, 131.31, 133.02, 137.42, 138.58, 138.89, 139.54, 140.44, 141.14,158.05. The red crystals of (MesPDPPh)UO2(THF) suitable for SCXRD were grown from a mixture of tolueneand pentane at −30 °C. Anal. Calcd for C47H45N3O3U (mol. wt. 937.924 g/mol): C,60.19; H, 4.84; N, 4.48. Found: C, 60.79; H, 4.82; N, 4.38.In the glovebox, a20 mL scintillation vial equipped with a magneticstirrer was loaded with H2Cl2PhPDPPh  and 2 mL of diethylether, affording a clear, homogeneous solution. In a separate vial,LiHMDS  was dissolved in approximately2 mL of diethyl ether. The LiHMDS solution was added to the solutionof H2Cl2PhPDPPh with vigorous stirring,inducing an immediate color change to a brilliant luminescent yellow,accompanied by the dissolution of all the solids. The resulting solutionwas stirred for approximately 2 h. In a separate vial, [UO2Cl2(THF)2]2  was suspended in 3 mL of diethyl ether and added dropwiseto the suspension of Li2Cl2PhPDPPh, inducing an immediate color change to dark-red/brown. The mixturewas stirred for 16 h, at which time the resulting suspension was filteredover a 1″ pad of Celite in a glass pipette plugged with a microfiberglass filter. A brown powder was collected on the Celite column andwashed with three 2 mL aliquots of pentane. The material was thenextracted from the Celite plug using 10 mL of DCM. The red-brown extractswere collected and volatiles were removed in vacuo. The residue wasthen extracted into benzene and passed through an additional Celiteplug, collected in a tared, 20 mL scintillation vial, and reducedto dryness. The resulting dark residue was triturated with pentane,leaving a brown powder that was identified as the title compound.Yield: 0.190 g, 0.192 mmol, 62%. Red, single crystals of (Cl2PhPDPPh)UO2(THF) suitable for SCXRD were grownfrom the diffusion of pentane into a toluene solution of the compound. 1H NMR : δ 7.76, 7.46 , 7.26 , 7.15–7.13 , 6.99 , 6.91 , 6.64 , 6.46 , 4.04 , 1.45 . 13C NMR : δ 26.60,77.40, 115.17, 117.03, 126.81, 128.33, 128.59, 128.74, 130.72, 131.20,136.90, 137.35, 138.89, 138.94, 139.26, 156.66. One resonance wasnot detected. Anal. Calcd for C41H29Cl4N3O3U (mol. wt. 991.530 g/mol): C, 49.67; H,2.95; N, 4.24. Found: C, 49.81; H, 2.80; N, 4.12.In the glovebox, a 20 mL scintillation vial equippedwith a magnetic stirrer was loaded with H1H and 13C{1H} NMR spectra wererecorded at room temperature ona 400 MHz Bruker AVANCE spectrometer or a 500 MHz Bruker AVANCE spectrometerlocked on the signal of deuterated solvents. All the chemical shiftsare reported relative to SiMe4 using 1H chemical shifts of the solvent as a secondary standard. The Fouriertransform IR (FT-IR) spectra of compounds were recorded on a ShimadzuIRAffinity-1 FT-IR spectrophotometer and are reported in wavenumbers(cm–1). Electronic absorption measurements wererecorded at room temperature in anhydrous tetrahydrofuran (THF) insealed 1 cm quartz cuvettes using an Agilent Cary 60 UV–Visspectrophotometer. CV experiments were performed at room temperaturein an MBraun inert atmosphere drybox containing an atmosphere of purifiednitrogen using a Bio-Logic SP200 potentiostat/galvanostat and theEC-Lab software suite. A three-electrode system cell configurationthat consisted of a glassy carbon (ø = 3.0 mm) as the workingelectrode , a platinum wire as the counter electrode, and a silver wire as the quasi-reference electrodewas employed. All the CV measurements utilized 1 mM sample solutionsin THF or DCM with 0.1 M tetrabutylammonium hexafluorophosphate asthe supporting electrolyte. Ferrocene (Fc) was added as an internalstandard after the completion of the measurements, and all potentialswere referenced versus the Fc+/Fc0 couple. Elementalanalysis data were obtained from the Elemental Analysis Facility atthe University of Rochester. Microanalysis samples were weighed witha PerkinElmer model AD6000 Autobalance and their compositions weredetermined with a PerkinElmer 2400 Series II analyzer. Air-sensitivesamples were handled in a VAC Atmospheres glovebox.(MesPDPPh)UO2(THF) and (Cl2PhPDPPh)UO2(THF) were mountedon a thin glass optical fiber or a nylonloop and mounted on a Rigaku XtaLAB Synergy-S Dualflex diffractometerequipped with a HyPix-6000HE HPC area detector for data collectionat 100.00(10) K. A preliminary set of cell constants and an orientationmatrix were calculated from a small sampling of reflections.76 A short pre-experiment was run, from which anoptimal data collection strategy was determined. In the case of complex (MesPDPPh)UO2(THF), the full data collection was carried out using a PhotonJet (Cu)X-ray source, whereas data collection for (Cl2PhPDPPh)UO2(THF) was performedusing a PhotonJet (Mo) X-ray source. After the intensity data werecorrected for absorption, the final cell constants were calculatedfrom the xyz centroids of the strong reflections from the actual datacollections after integration.76 See the Supporting Information file for additional crystaland refinement information. The structure was solved using SHELXT77 and refined using SHELXL.78 Most or all non-hydrogen atoms were assigned from the solution.Full-matrix least squares/difference Fourier cycles were performed,which located any remaining non-hydrogen atoms. All the non-hydrogenatoms were refined with anisotropic displacement parameters. All thehydrogen atoms were placed in ideal positions and refined as ridingatoms with relative isotropic displacement parameters.The single crystals of complexes 80 Geometry optimizations used the PBE functional81 and were accelerated using the resolution of identity (RI)approximation.83 Scalar-relativistic effects wereincluded via the zeroth-order regular approximation(ZORA)84 using relativistically recontractedtriple-ζ quality basis sets, ZORA-def2-TZVP85 on nitrogen and oxygen atoms and SARC-ZORA-TZVP86 for uranium. All the other atoms were handledwith the recontracted split-valence ZORA-def2-SVP basis set.85 Noncovalent interactions were considered viaatom-pairwise dispersion corrections with Becke–Johnson (D3BJ)damping.88 The TD-DFT calculations used the B3LYP densityfunctional89 and were accelerated usingthe RIJCOSX approximation.91 Relativistic effectswere included using the Douglas–Kroll–Hess (DKH) Hamiltonianwith DKH-specific basis sets analogous to those used in the geometryoptimizations. The Tamm–Dancoff approximation was not used,and the effects of spin–orbit coupling (SOC) were probed usinga spin–orbit mean field (SOMF) approach.92 All the solvation effects were handled using the conductor-likepolarizable continuum model (C-PCM) and a Gaussian charge scheme.93All the calculations were performedusing the ORCA quantum chemical program package v5.0.1.62 the in situ preparationof the reported PDP dilithium salts Li2ArPDPPh of the corresponding pyridine dipyrrole compounds H2ArPDPPh was chosen as a convenient syntheticaccess point to metathesis chemistry with the popular nonaqueous uranylstarting material [UO2Cl2(THF)2]2.75 Upon the addition of a diethylether slurry of [UO2Cl2(THF)2]2 to a slurry of in situ prepared Li2MesPDPPh in the same solvent, an immediate color change froma luminescent yellow to a dark-red/brown was observed. This colorchange was accompanied by the dissolution of all the solids. The reactionmixture was stirred overnight at room temperature, at which time theformation of a brown precipitate was evident. Following filtrationand workup (see MesPDPPh)UO2(THF) was obtained in 53% yield (vide infra). Furthermore,it was determined that (MesPDPPh)UO2(THF) was amenable to additional purification by means of recrystallization(vide infra) by the diffusion of pentane into a saturated toluenesolution of the compound.Followingliterature protocols,MesPDPPh)UO2(THF) was accomplished by IR spectroscopy . A spectrum obtained from a bulk powdersample of the compound revealed no indication of pyrrole N–Hstretches, consistent with successful deprotonation and metalationof both pyrrolide nitrogens. A prominent band was identified at afrequency of 917 cm–1, attributed to the asymmetric(νasym) O=U=O stretch of (MesPDPPh)UO2(THF).94 This value is in excellent agreement with that of a macrocylic dipyrrolidetetraimine uranyl complex reported by Sessler and co-workers, characterizedby a νasym O=U=O stretch at 910 cm–1.10The initial characterization of (MesPDPPh)UO2(THF) was also performedby means of 1H and 13C{1H} NMR spectroscopyat roomtemperature in benzene-d6 (C6D6). Both the spectra revealed the expected number ofresonances with relative integrations (1H NMR), consistentwith a Cv2 symmetricstructure in the solution . Moreover, closer inspection revealed a diagnostic singlet resonanceat 6.52 ppm, corresponding to the 4-pyrrolide hydrogens of (MesPDPPh)UO2(THF). The 4-pyridyl proton, alsoroutinely used as a convenient spectroscopic handle for PDP compounds,was located at 7.14 ppm, overlapping with a singlet signal attributedto the meta protons of the 5-pyrrolide mesityl substituent.Resonances assigned to the two methylene groups of a bound THF ligandwere identified at 4.01 and 1.98 ppm, respectively. The integrationsof these two signals were consistent with a 1:1 PDP ligand to THFratio, which agrees with the proposed assignment as a monosolvateduranyl complex. The 1H NMR spectra obtained from the samplesof (MesPDPPh)UO2(THF) following prolongedexposure to dynamic vacuum did not reveal any changes in the relativeintegration of the resonances corresponding to the coordinated THFligand, consistent with its retention under these conditions. However,(MesPDPPh)UO2(THF) was determinedto engage in facile ligand substitution with stronger Lewis bases.For example, the addition of 1 equiv of 4-dimethylaminopyridine (DMAP)to a benzene-d6 solution of (MesPDPPh)UO2(THF) was found to readily displacethe coordinated THF ligand, resulting in the formation of the correspondingDMAP adduct, (MesPDPPh)UO2(DMAP),as ascertained by 1H NMR spectroscopy .Furthermore, spectroscopic characterizationof (MesPDPPh)UO2(THF) was obtainedby SCXRD (MesPDPPh)UO2(THF)suitable for analysis. The SCXRD study (100.00(10) K) confirmed theidentity of the compound as the six-coordinate species (MesPDPPh)UO2(THF), which had crystallized in themonoclinic space group I2/a. AnORTEP representation of the molecular structure demonstrates thatthe solid-state structure is consistent with the apparent Cv2 point group symmetry inferredfrom the solution phase 1H and 13C{1H} NMR spectroscopic studies. The equatorial positions of the distortedoctahedral compound are defined by the meridional N3 (MesPDPPh) chelate and THF ligands, of which, theequatorial bond angles sum to 360.09°. Moreover, due to the biteangle enforced by the rigid MesPDPPh2– ligand, which routinely enforces N1–M–N3 bond anglesof less than 140°, a significant deviation from an idealizedoctahedral geometry is noted for (MesPDPPh)UO2(THF), which contains an N1–U–N3 bond angleof 129.05(8)°. Additionally, a deviation from planarity arisesfrom the pyridine of the PDP chelate folding below the plane establishedby the remainder of the PDP chelate UO2(THF) is noteworthy, as often thelarge ionic radius of uraniumresults in uranyl compounds with coordination numbers of seven, formononuclear species. This holds true for most pincer uranyl complexes,51 with the PDI uranyl complexes, Cp*UO2(MesPDIMe) and Cp*UO2(tBu-MesPDIMe) N=CMe)2C5H3N; tBu-MesPDIMe = 2,6-((Mes)–N=CMe)2-p-C(CH3)3C5H2N; Me = methyl), reported by Bart and co-workers being notable exceptions.52 In these instances, the six-coordinate geometryresults as a function of a bulky Cp* ligand, positioned trans to the PDI pyridine nitrogen and approximately orthogonal to theplane of the chelate ligand. Such an orientation presumably rendersa coordination number higher than six unlikely for this class of compounds.Similarly, the steric bulk of the flanking mesityl groups presentin (MesPDPPh)UO2(THF) prohibits accessof an additional THF solvent ligand within the plane of the PDP chelate,disallowing the possibility of a seven-coordinate species [see Figure S20 for a space-filling representationof (MesPDPPh)UO2(THF)].The six-coordinate geometry of (MesPDPPh)UO2(THF) include uranium-oxo (U-Oyl) bondlengths of 1.773(2) and 1.774(2) Å for U(1)–O(1) and U(1)–O(2),respectively. These distances are typical for UVI coordinationcomplexes.95 For example, the uranyl PNPpincer complex, (PNP)2UO2 reported by Kiplingerand co-workers has U–Oyl bond lengths of 1.791(6)and 1.808(6) Å.31 Similar U–Oyl bond lengths (1.7792(12) and 1.7796(12) Å) have beenreported previously by Liddle and co-workers for the pincer type uranylcomplex, [U(BIPMMesH)O2(Cl) (THF)].96 In the case of (MesPDPPh)UO2(THF) the oxo ligands are trans to one another, withan O(1)-U(1)-O(2) bond angle slightly deviated from linearity (173.94(9)°).The U(1)–N(2) (U-Npyridine) and U(1)–O(3)(U-OTHF) bond distances for (MesPDPPh)UO2(THF) are 2.535(2) and 2.3917(19) Å, respectively.For comparison, the U–Npyridine bond distance isshorter than that of the pyridine-2,6-dicarboxamide complex uranylcomplex UO2Cl2L97  possessing(U–Npyridine 2.634(2) Å); however, the U–OTHF distance is in good agreement with the average U–OTHF bond distance found in [UO2Cl2(THF)2]2 (2.40(3) Å).98 Completing the primary coordination sphere, the (MesPDPPh)UO2(THF) U–Npyrrole contacts,U(1)–N(1) and U(1)–N(3), were determined to be 2.354(2)and 2.356(2) Å, which are shorter than in dipyriamethyrin anddipyrrinate analogues.48 It is proposed that the shorterU–Npyridine and U–Npyrrole contactsmay occur as a result of a combination of steric and electronic effects,including a size matching between the coordination environment establishedby the (MesPDPPh)2– ligandand the uranyl moiety and the pi-donor character of the pyrrolidenitrogens.Otherimportant structural metrics for (MesPDPPh)UO2(THF) in hand,we next targeted the preparation of the (Cl2PhPDPPh)UO2(THF) analogue by the extension of the same generalsynthetic protocol (2Cl2(THF)2]2 to a slurry of in situprepared Li2Cl2PhPDPPh in the samesolvent, followed by filtration and workup, provided (Cl2PhPDPPh)UO2(THF) in a 62% isolated yield as apolycrystalline brown powder. A solid-state IR spectrum acquired ona bulk powder sample indicated no pyrrole N–H stretching modes,consistent with metalation, and a νasym O=U=Ostretch located at 930 cm–1, blue shifted relativeto the same feature for (MesPDPPh)UO2(THF) . 1H and 13C{1H} NMR spectroscopic analysis of (ClPh2PDPPh)UO2(THF) in benzene-d6 at room temperature revealed the expected number ofresonances with relative integrations consistent with a Cv2 symmetric structure in the solution. This result isconsistent with either (1) a solution-phase structure where the ortho-chloride substituents interact with the uranium centerbut rapidly interconvert on the timescale of the NMR experiment, or(2) the ortho-chloride substituents do not interactwith the uranium center.62 A diagnosticsinglet resonance assigned to the 4-pyrrolide hydrogens of (Cl2PhPDPPh)UO2(THF) was identified at 6.91 ppm,shifted significantly downfield relative to the same protons in themesityl analogue. A triplet resonance located at 6.64 ppm in the spectrumof (Cl2PhPDPPh)UO2(THF) was assignedto the 4-pyridyl proton, upfield relative to the same proton in (MesPDPPh)UO2(THF). Resonances correspondingto a bound THF ligand were located at 1.45 and 4.04 ppm, respectively,with integrations consistent with a 1:1 THF/Cl2PDPPh ligand ratio.With (protocol 1. The adCl2PhPDPPh)UO2(THF) were obtained from the diffusionof pentane into a concentratedtoluene solution of the compound (Cl2PhPDPPh)UO2(THF) and (MesPDPPh)UO2(THF). First, despite similar crystallization conditionsfor the two compounds (the diffusion of pentane into a concentratedtoluene solution), (Cl2PhPDPPh)UO2(THF) crystallizes as a toluene solvate in the monoclinic space group P21/n. Second, one of the PDPCl2Ph groups in (Cl2PhPDPPh)UO2(THF) is canted, whereas the second Cl2Ph groupis approximately perpendicular to the chelate plane, similar to bothmesityl substitudents in (MesPDPPh)UO2(THF). As a consequence, the ortho chlorides inthe canted Cl2Ph group have distances to the uranium centerof 3.503 Å (U1–Cl1) and 5.503 Å (U1–Cl2),whereas the other Cl2Ph group has U–Cl distancesof 4.688 Å (U1–Cl3) and 4.488 Å (U1–Cl4),respectively. The U1–Cl1 distance in (Cl2PhPDPPh)UO2(THF) is significantly longer than Cl →U dative interactions (3.006(4)–3.227 (3) Å) involvingthe ortho-Cl atoms of C6Cl5 ligands in a pair of U(IV) complexes characterized by Hayton andco-workers.99 Moreover, the solid-statestructure of (Cl2PhPDPPh)UO2(THF)is C1 symmetric. This result is inconsistentwith the NMR data, which indicates that the complex possesses Cv2 symmetry in the solution.We propose that in the solution, (Cl2PhPDPPh)UO2(THF) does not engage in any interactions with the ortho-chlorides, or that there is fast equilibrium of theCl2Ph moieties on the NMR timescale. Despite the differencesthat the Cl2Ph2 substitution pattern impartsrelative to the mesityl analogue, the remainder of the structure of(Cl2PhPDPPh)UO2(THF) is consistentwith that of (MesPDPPh)UO2(THF).The uranyl bond lengths were determined to be 1.771(3) Å (U(1)–O(1))and 1.771(2) Å (U(1)–O(2)) and the O(1)–U(1)–O(2)bond angle is 174.67(11)°. The primary coordination sphere iscompleted by bonds to the PDP pincer nitrogens (U(1)–N(X)  lengths of 2.381(3), 2.504(3),and 2.367(3) Å), and to the THF oxygen, (U(1)–O(3)) witha bond distance of 2.408(2) Å. The O(3)–U(1)–N(2)and N(3)–U(1)–N(1) bond angles were determined to be174.76(10) and 130.61(9)°, respectively. A summary of selectedbond lengths and angles for both (Cl2PhPDPPh)UO2(THF) and (MesPDPPh)UO2(THF) is provided in The red single crystals of (compound 1. ImportArPDPPh)UO2(L)complexes, we next pursued studies aimed at investigating the electrochemicalproperties of these compounds by means of cyclic voltammetry UO2(THF) and (Cl2PhPDPPh)UO2(THF) were conducted on 1 mM solutionsof the indicated compound in THF with 100 mM tetrabutylammonium hexafluorophosphate([nBu4N][PF6]) as the supportingelectrolyte. For (MesPDPPh)UO2(THF),scanning anodically revealed a feature at 0.30 V (vs Fc+/0). This redox event is tentatively assigned as an oxidation of thePDP chelate ligand, as the uranyl center is in its fully oxidized(UVI) state. Noteworthy is that this event is cathodicallyshifted by over 200 mV relative to an analogous redox process forthe Zr bis-PDP complex Zr(MesPDPPh)2 (E1/2 = 0.53 V vs Fc+/0).67 The apparent reversibility of this couple issurprising, as to date, Zr(MesPDPPh)2 is the only reported PDP complex to have reversible oxidative ligandchemistry. This is a consequence of the sterically protected pyrrolidefunctionality, which is normally susceptible to degradation underoxidizing conditions.100Having established a firm understanding of the solution-and solid-statestructures of both  is observed .Given the documented electrochemical stability of PDP ligands at similarpotentials, we ascribed this event to a UVI/UV redox couple.69 The reduction of the uraniumcenter resembles values reported previously for the UVI/UV redox couple for a number of uranyl compounds withnitrogen-based ligands, albeit anodically shifted by ∼100 mVin all cases.95 For example, the UVI/UV reduction potential UO2(Ar2nacnac) (hfac) NC(Me)CHC(Me)N],hfac = hexafluoroacetylacetonate) reported by Hayton is −1.39V versus Fc+/0.101 Furthermore,similar UVI/UV reduction potentials (−1.32and −1.36 V vs Fc+/0) have also been documentedby Blakemore and co-workers for recently characterized heterobimetallicuranyl complexes.102 An additional irreversiblereduction event is observed (Epc = −3.07V vs Fc+/0) and assigned as a one-electron reduction ofthe PDP chelate . Similar eventsat highly reducing potentials are well documented for previously reportedtransition metal PDP complexes; studies of reduced PDP Cr complexeshave confirmed the nature of these events to be ligand based.69When scanning cathodically, a reversible reduction eventcenteredat −1.22 V (vs FcCl2PhPDPPh)UO2(THF) possessed similar features tothat observedin the voltammagram of (MesPDPPh)UO2(THF). A reversible redox event is observed at 0.32 V versus Fc/Fc+ and is assigned as a ligand-based oxidation. The oxidationis shifted by 20 mV relative to (MesPDPPh)UO2(THF), consistent with the electron-withdrawing nature ofthe dichlorophenyl substituents of the pyrrolide moieties. Cathodicscans revealed a reversible reduction event centered at −1.15V versus Fc+/0 . This feature is shifted anodicallyby 70 mV relative to the analogous process for (MesPDPPh)UO2(THF), suggesting the electron-withdrawingnature of the ligand further stabilizes the reduction of the uranylion. The electrochemical behavior of (Cl2PhPDPPh)UO2(THF) at extremely reducing potentials was similarto that of (MesPDPPh)UO2(THF), witha second reduction event assigned to the PDP ligand at −3.26V. However, unlike (MesPDPPh)UO2(THF),in the case of (Cl2PhPDPPh)UO2(THF),this reduction event is entirely irreversible. Notably, the quasi-reversibleUVI/V redox process became strictly irreversible in thesescans, supporting the rapid and complete decomposition of (Cl2PhPDPPh)UO2(THF) upon its two-electron reduction. Although the reason for thisdisparate behavior is not clear at this time, we propose that furtherone-electron reduction of putatitive [(Cl2PhPDPPh)UO2(THF)]1– may result in reductivecleavage of an aryl chloride bond of one of the 2,6-dichlorophenylsubstituents. Consistent with this hypothesis, the irreversible single-electronreduction of chlorobenzene has been reported at −3.23 V andresults in the formation of an aryl radical and a chloride anion.103 Although outer-sphere fluoride abstractionfrom the [NnBu4][PF6] supportingelectrolyte could offer a similar halide-promoted degradation pathway,this possibility is disfavored in light of the quasi-reversible redoxbehavior observed for (MesPDPPh)UO2(THF) under the same experimental conditions.The electrochemical profile of (MesPDPPh)UO2(THF) and (Cl2PhPDPPh)UO2(THF) inthe solution phase we turned to electronicabsorption spectroscopy. The spectra of both species in the THF solutionare essentially identical and are dominated by two charge-transfer bands at 326 and 424 nm  for (MesPDPPh)UO2(THF) and 328 and 422 nm  for (Cl2PhPDPPh)UO2(THF), respectively. It is noted thatboth complexes also weakly absorb past 500 nm. The electronic absorptionspectra of both compounds are thus qualitatively similar to that ofSessler’s related pyrihexaphyrin (0.0.0.0.1.0)-uranyl complex,albeit only below 500 nm.23 Fortier’s familyof DMAP-ligated bis-dipyrrinate compounds, which also have two pyrrolideand one pyridine donor, also possess similar charge-transfer bands,although the lower energy band, assigned as dipyrrin to uranium ligand-to-metalcharge transfer (LMCT), is redshifted to 462–472 nm.48In order to interrogatethe optical properties of (MesPDPPh)UO2(THF) using ORCA quantum chemicalprogram package v5.0.1. The C-PCM was utilized to account for solvationeffects. Overall, the agreement between the calculated and experimentalspectra is quite good . Unfortunately, the lowest energy transitions are incrediblyweak (1–S4 (the strongestlow-energy transitions) are exclusively LMCT in character .This is further evidenced by a Mulliken population analysis on theground and excited states which shows a charge reduction on uraniumof nearly a full electron (57) and 417 nm (S32), respectively, are primarily a π–π*transitions, although some LMCT character is mixed in To gain further insight into the nature of the transitions in theelectronic absorbance spectra of PDP complexes, time-dependent densityfunctional theory (TD-DFT) calculations were undertaken on UO2(THF) and(Cl2PhPDPPh)UO2(THF), which havebeen thoroughly characterized by a variety of physical methods anda complementary TD-DFT study. Notably, the steric pressure impartedby the bulky aryl substituted PDP chelates results in six-coordinatedistorted octahedral complexes in both the solid- and solution-state.The electronic absorption spectrum of (MesPDPPh)UO2(THF) is dominated by two charge-transfer bands at326 and 424 nm with predominantly π–π* character,similar to previously reported uranyl complexes carrying pyrrole-basedligands, while the strongest transitions in the 500–600 nmregion are assigned as LMCT. In THF solution, both (MesPDPPh)UO2(THF) and (Cl2PhPDPPh)UO2(THF) have been found to demonstrate richelectrochemistry, with reversible ligand-based oxidative chemistryand an apparent UVI/UV reduction couple, whichsuggests that a reduced UV analogue may be chemically isolable.In summary, we envision that this report will lay the foundation forfuture investigations of PDP actinide coordination and organometallicchemistry, including reactivity and photophysical studies.We report the synthesis and characterizationof two PDP uranylcomplexes, (