The objective of this study is to explore the long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) expression profiles of monocyte-derived dendritic cells (DCs) obtained from peripheral blood mononuclear cells (PBMCs). DCs are known to play a major role in the regulating function of allergic rhinitis (AR).PBMCs were separately isolated from the human peripheral blood of patients with AR and normal person (NP). The mixed lymphocyte reaction (MLR) assay was used to evaluate the function of DCs. Flow cytometry was used to determine the immune regulatory function of immature DCs (imDCs) and mature DCs (mDCs). lncRNAs and mRNAs in the NP group (DCs isolated from NP) and the test group (DCs isolated from patients with AR) were identified via chip technology and bioinformatic analyses. Moreover, bioinformatic analyses were employed to identify the related biological functions of monocyte-derived DCs and construct the functional networks of lncRNAs and mRNAs that are differentially expressed (DE) in imDCs and mDCs.p < 0.001). We identified 962 DE lncRNAs and 308 DE mRNAs in the imDCs of NP and patients with AR. Additionally, there were 601 DE lncRNAs and 168 DE mRNAs in the mDCs in the NP and test groups. Quantitative RT-qPCR was used to study the significant fold changes of lncRNAs and mRNAs. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found 16 significant regulated pathways in imDCs and 10 significant regulated pathways in mDCs, including the phagosome, cell adhesion signaling pathway, and inflammatory mediator regulation of TRP channels pathway.MLR was significantly higher in the mDCs group than that in the imDCs group. CD14 was highly expressed in imDCs, whereas HLA-DR, CD80, and CD86 were highly expressed in mDCs (Our research studied the lncRNA and mRNA expression profiles of monocyte-derived DCs and demonstrated the functional networks that are involved in monocyte-derived DCs-mediated regulation in AR. These results provided possible molecular mechanisms of monocyte-derived DCs in the immunoregulating function and laid the foundation for the molecular therapeutic targets of AR. Allergic rhinitis (AR) is a very common allergic disease that affects 10–40% of the global population . Its remDendritic cells (DCs), which are the most important antigen-presenting cells (APCs) that send signals to the T cells, mainly participate in the pathogenesis of many diseases with immunoregulatory mechanisms, such as AR. DCs link the innate and adaptive immune responses. The peripheral blood mononuclear cells (PBMCs) have a round nucleus . PBMCs iLong non-coding RNAs (lncRNAs), over 200 nt in length, is a type of RNA that does not a protein coding function . These RThe combination of lncRNA–messenger RNA (mRNA) expression profiles and functional networks is adopted to analyze the DC-mediated regulation functions. These results improve our understanding of lncRNAs in the immunoregulatory function of monocyte-derived DCs and indicate the potential targets for the curative treatment of AR.Patients with AR visited doctors in the outpatient service in the Guo Yi Tang of Beijing University of Chinese Medicine. In this study, there were 24 subjects: 12 males and 12 females. They were divided into two groups: the AR group  and NP group . With support/approval from the Ethics Committee of Beijing University of Chinese Medicine, this study was conducted while adhering to the principles of the Declaration of Helsinki. Patients in the AR group were positive for skin puncture test, including pollen, food, dust mites, paint, or molds as well as in specific IgE. Two weeks before study recruitment, these patients with AR received no topical or systemic corticosteroid therapy. We chose the study participants with no history of smoking or other immune system disorders, such as rheumatoid arthritis, systemic lupus erythematosus, and scleroderma.L-glutamine . After incubation at 37°C for 2 h, the non-adherent cells were removed and the adherent cells were cultured within the medium containing 100 ng/ml of rhGM-CSF and 100 ng/ml of rhIL-4 . On the sixth day, 50 ng/ml of TNF-α  was added into the samples; the method had the same protocol in the study of The whole blood samples obtained from the two groups were stored in vacuum tubes with heparin, and PBMCs were isolated from these samples by lymphocyte separation solution . Mononuclear cells were seeded in 12-well plates with the RPMI 1640 medium that contains 10% heat-inactivated fetal calf serum  and 2 mM of 8 cells per well at a quantity of 200 μl and incubated with non-adherent PBMCs obtained from the same healthy people. These samples were later stimulated by lymphocytes in the concentration proportions of 1:10, 1:50, and 1:100. Thereafter, the samples were mixed and incubated with non-adherent PBMC from the same healthy persons at the same concentrations in triplicate. The cells were treated with 10% fetal bovine serum. Then, 10 μl of 3--2,5-diphenyl-2H-tetrazolium bromide (MTT) solution  was added to each well, and the cells were incubated for 72 h in the incubator. Then, 150 μl of DMSO was added followed by the addition of enzymes after 4 h. The absorbance was detected using a spectrophotometer at 570 nm.After being treated with 25 μg/mL of mitomycin at 37°C for 30 min, the DCs were placed at the concentrations of 2 × 10g for 5 min. Data were acquired using a FACSCalibur cytometer  and the ratios of CD14+, HLA-DR+, CD80+, and CD86+ DCs were determined.The CD14 , HLA-DR , and isotype mouse IgG2a-PE  were added in the samples of imDCs. Moreover, CD86-APC, CD80-PE, and isotype mouse IgG1–FITC  were added in the samples of mDCs. The cells were then suspended with precooled PBS, counted under a microscope, and centrifuged at 1000 ∗180K, Design ID: 062918). All the chip results were detailed according to the processes of software operations. The screening criteria were to increase or decrease the fold change value ≥ 2.0 and p-value < 0.05.The RNA extraction, labeling, chip hybridization, and scanning were all finished following the use of Agilent Human lncRNA–mRNA profiling chip  enrichment analysis were used to study the differentially expressed (DE) mRNAs. The results of the target gene analysis of lncRNA and the mRNA expression results on the chip need to be correlated so that the upregulated and downregulated DE genes can be investigated. The corrected p-value < 0.05, FDR < 0.05) were screened. The co-expression network of lncRNAs and mRNAs was constructed, and the co-expression network of lncRNAs and mRNAs was then established.The correlation of the lncRNA–mRNA expression in the imDCs and mDCs was calculated. Then, the relationship pairs of LncRNA and mRNA based on the abovementioned criteria  and reverse transcriptase  to analyze the qPCR results. The thermal cycler conditions were set as follows: amplificated at 95°C for 10 min, 95°C for 15 s, 60°C for 60 s, 40 cycles of denaturation , 15 s at 95°C, and a combined process of annealing and extension . p-values < 0.05 were considered significant values for this study.The SPSS 22.0 software was used for statistical analysis in this study. Results were expressed as mean ± standard deviation. The relationship of lncRNAs and mRNAs was determined by the Spearman’s correlation coefficient. p < 0.001).In allergenic mixed lymphocyte reaction (MLR), the levels of T-cell proliferation were increased with the proportion of T cells. DCs in the patients with AR have a stronger stimulation ability than NP as shown in + DCs in the patients with AR was 0.84 ± 0.25% (median: 0.78%), and it was significantly lower than the value in the NP group (p = 0.0008), where the mean percentage of these cells was 0.012 ± 0.013% (median: 0.017%)  .+ mDCs in the patients with AR was 44.25 ± 8.64% (median: 44.8%) and was higher (p = 0.0006) than the NP group, where the mean percentage of these cells was 95.3 ± 3.84% (median: 99.0%) (The mean proportion of HLA-DR: 99.0%) .+ mDCs in the patients with AR was 72.15 ± 7.64% (median: 67.78%) and was higher (p = 0.0003) than the NP group, where the mean percentage of these cells was 95.3 ± 3.84% (median: 96.92%) (The mean proportion of CD80 96.92%) .+ mDCs in the patients with AR was 62.15 ± 7.64% (median: 64.69%) and was higher (p = 0.006) than the control group, where the mean percentage of these cells was 92.3 ± 5.84% (median: 95.12%) (The mean proportion of CD86 95.12%) .In total, 308 DE mRNAs, including 175 upregulated mRNAs and 133 downregulated mRNAs, were found in the imDCs of patients with AR and NP. A clustergram  and volcIn total, 962 DE lncRNAs, including 434 upregulated and 528 downregulated lncRNAs, were found in patients with AR and NP. The clustergram  and volcWe identified 268 target genes after analyzing the possible DE lncRNAs target genes in imDCs. Additionally, we also investigated the possible presence of DE lncRNA target genes in mDCs. In our study, 99 target genes were identified in these DE lncRNAs. RT-qPCR was used to evaluate DE mRNAs and lncRNAs to verify our RNA chip results. We randomly detected three lncRNAs and 10 mRNAs. MARCO, KIR2DS3, F11R, HLA-B, HLA-C, NON-HSAG046717, and NON-HSAT089067 were upregulated, whereas ITGAV, CD36, IFNB1, PTAFR, HLA-DQB1, NON-HSAT 059748, NON-HSAT024276, and NON-HSAT098958 were downregulated. The results of RT-qPCR were consistent with those of RNA chip results, hence confirming that our chip data were reliable .in vitro from patients with AR and the NPs. Besides that, we used RT-qPCR to confirm these findings. Our KEGG pathway analysis (In our research, we used rhGM-CSF, rhIL-4, and TNF-α to induce the mDCs from PBMCs. The generation of human monocyte-derived DCs from whole blood was recognized by all the scientists . We inveanalysis , 6 indicin vitro techniques allow the in vitro differentiation of DCs (Dendritic cells play a central role in allergic inflammation . The latn of DCs . Their an of DCs . In MLR n of DCs . DCs areMore number of studies have focused on exploring the mRNA expressed in DCs, but none have been conducted to reveal which and how mRNA affects DCs in patients with AR. To investigate the mechanism of DCs’ functions in patients with AR, the mRNA expression profile was determined and bioinformatics analysis was performed in our study. In total, 308 mRNAs were identified in the analysis. Among these DE genes, HLA-C, ITGAV, MARCO, CD36, IFNB1, and KIR2DS3 were found to be most significantly upregulated in the imDCs’ network. HLA-C plays an important role in promoting differential DC maturation . ITGAV iThe imDCs migrate to the lymphoid organs that will be matured in the future. They present captured Ag to the naïve T cells . Hence, Long non-coding RNA is an important component in the mRNA expression profiles . SeveralLong non-coding RNAs do not have a protein coding function, but they can be used as a new modulator, such as cis- or trans-gene regulating expression, demethylation-promoting effect, and mRNA-processing control were the major mechanisms . To analWe used RT-qPCR to validate the mRNA–lncRNA chip results with only one randomly selected transcript, and found that the RT-qPCR results are consistent with the chip results in better understanding the role of lncRNA in the pathogenesis of DC-mediated AR.In summary, our study proved that several mRNAs and lncRNAs of DC affect a certain process of AR pathogenesis by regulating the target genes. This result points out the direction for future studies on determining and explaining the functions and mechanisms of AR-related mRNA and lncRNA, and provides new therapeutic targets for patients with AR.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by the medical and experimental animal ethics committee of Beijing University of Traditional Chinese Medicine. The patients/participants provided their written informed consent to participate in this study.YZ, XC, and YZ carried out the experiments. JW, QW, YZ, XC, and YZ designed the study and edited the manuscript. All authors read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Background: Remote virtual rehabilitation aroused growing interest in the last decades, and its role has gained importance following the recent spread of COVID19 pandemic. The advantages of virtual reality (VR), augmented reality (AR), gamification, and telerehabilitation have been demonstrated in several medical fields. In this review, we searched the literature for studies using these technologies for orthopedic rehabilitation and analyzed studies’ quality, type and field of rehabilitation, patients’ characteristics, and outcomes to describe the state of the art of VR, AR, gamification, and telerehabilitation for orthopedic rehabilitation. Methods: A comprehensive search on PubMed, Medline, Cochrane, CINAHL, and Embase databases was conducted. This review was performed according to PRISMA guidelines. Studies published between 2015 and 2020 about remote virtual rehabilitations for orthopedic patients were selected. The Methodological Index for Non-Randomized Studies (MINORS) and Cochrane Risk-of-Bias assessment tool were used for quality assessment. Results: 24 studies  and 15 non-randomized studies) and 2472 patients were included. Studies mainly concern telerehabilitation (56%), and to a lesser extent VR (28%), AR (28%), and gamification (16%). Remote virtual technologies were used following knee and hip arthroplasty. The majority of included patients were between 40 and 60 years old and had a university degree. Remote virtual rehabilitation was not inferior to face-to-face therapy, and physical improvements were demonstrated by increased clinical scores. Orthopedic virtual remote rehabilitation decreased costs related to transports, hospitalizations, and readmissions. Conclusion: The heterogeneity of included studies prevented a meta-analysis of their results. Age and social context influence adaptability to technology, and this can modify compliance to treatment and outcomes. A good relationship between patient and physiotherapist is essential for treatment compliance and new technologies are useful to maintain clinical interactions remotely. Remote virtual technologies allow the delivery of high-quality care at reduced costs. This is a necessity given the growing demand for orthopedic rehabilitation and increasing costs related to it. Future studies need to develop specific and objective methods to evaluate the clinical quality of new technologies and definitively demonstrate advantages of VR, AR, gamification, and telerehabilitation compared to face-to face orthopedic rehabilitation. Orthopedic rehabilitation is of paramount importance after a trauma or surgery to recover impaired function . A succeVR and AR aim to deceive the brain of patients by making them believe that they are in other places than the real one . In VR, The concept of gamification is based on the application of “game design elements in a non-game context” to motivate participation . BeneficTelerehabilitation is a branch of telemedicine that allows patients to communicate with their health care provider remotely during rehabilitation session .These technologies reduce patient hospitalization times and costs and increase the number of patients who can be treated at the same time . AnotherDespite these benefits, there are still many aspects of remote technologies for orthopedic rehabilitation that need to be analyzed and definitive conclusions about their advantages compared to face-to-face rehabilitation still need to be achieved .In this review, we searched the literature for studies using remote virtual technologies for orthopedic rehabilitation and analyzed studies’ quality, type and field of rehabilitation, patients’ characteristics, and outcomes to describe the state of the art of VR, AR, gamification, and Telerehabilitation for orthopedic rehabilitation.Literature search was performed according to PRISMA guidelines . PrelimiKeywords and combinations of keywords were used to search electronic databases and were organized according to the Population, Intervention, Comparison, Outcome (PICO) model as follows.Study: original studies with different study designs ; English language; articles published from 2015 to 2020.Participants: orthopedic patients.Interventions: remote virtual rehabilitations . Outcome measures: the primary outcome was to evaluate quantitative outcomes of remote virtual rehabilitation for orthopedic patients. The secondary outcome was to assess qualitative outcomes, patients’ characteristics such as age and social context, and costs. Other goals were to describe fields of orthopedic surgery and disease where remote virtual technologies were used. A comprehensive search on PubMed, Medline, Cochrane, CINAHL, and Embase databases was conducted. Keywords were combined using the Boolean operators “AND” and “OR”. The search strategy was iterative and flexible within the limits of the search engines of the individual databases. The following medical subject heading (MeSH) keywords and free terms were used for the search: rehabilitation, physiotherapy, remote rehabilitation, virtual rehabilitation, virtual reality, augmented reality, gamification, telerehabilitation, orthopedic, hip, knee, shoulder, elbow, wrist, hand, humerus, femur, spine, ankle, foot.Search strategies were checked by two reviewers (S.F. and L.G.).Exclusion criteria included: reviews, books, and protocol study.The systematic review was carried out in June 2020. Two researchers (S.F. and L.G.), independently reviewed all studies  that met inclusion criteria and extracted relevant data. A discussion among reviewers resolved disagreements.Two reviewers (S.F. and L.G.) independently evaluated the potential risk of bias of included studies using the Methodological Index for Non-randomized Studies (MINORS) , and theMINORSs’ items were scored 0 if not reported, 1 when reported but inadequate, 2 when reported and adequate. The global ideal score was 16 for non-comparative studies and 24 for comparative studies.The Cochrane Risk-of-Bias Tool assessed randomized controlled trials with the following criteria: selection, performance, detection, attrition, reporting, and other biases. All criteria were evaluated assigning 0 for low risk, 1 point for unclear, and 2 points for high risk of bias. The potential total score ranged 0–14. An overall score of 0–1 shows high quality, 2–3 moderate quality, and >3 low quality .Data about study design, number of patients, follow-up period, orthopedic surgery and disease, remote virtual technology used, patients’ age and social context, quantitative and qualitative outcome measures, and costs were extracted. Categorical variables were reported as percentage frequencies. Continuous variables were reported as mean, minimum, and maximum values.The selection process is illustrated in Studies included a total of 2472 of patients. Details about number of patients, study design, remote virtual rehabilitation technology, and follow-up are reported in The majority of the studies analyzed telerehabilitation (56%), 28% analyzed VR and AR, and 16% analyzed gamification.The follow-up of the studies was evaluated to understand the time needed to adapt to the technology. It was the preoperative period in 8% of the studies, 3 days in 4%, 10 days in 4%, 2 weeks in 4%, 3 weeks in 4%, 1 months in 4%, 2 months in 20%, 3 months in 8%, 4 months in 20%, 6 months in 12%, 17 months in 4%, 18 months in 4%, and 21 months in 4%.Age and social context were collected to analyze adaptability to technology in relation to these characteristics . The majRemote rehabilitation was tested mainly for total knee arthroplasty (TKA), total hip arthroplasty (THA), and unicompartmental knee arthroplasty (UKA) (73%). VR and AR were used for TKA (4%); chronic nonspecific low back pain (4%); and interventions of hip, knee, and ankle (1%). Gamification was implemented above all for rheumatoid arthritis (7%) and to a lesser extent for fracture of metacarpal (1%).The qualitative outcomes were used to understand how the patient qualifies the experienced with the new rehabilitation technology .Qualitative studies focused on costs, communication between patient and health care provider, user-friendliness, and perceived improvements.Costs were lower, mainly thanks to the reduction in travel expenses .Patients reported an increase in self-esteem themselves and an improved relationship with the physiotherapist despite the distance . Patients complained about difficult adaptation to the new technology at the beginning, but the majority described physical improvements . Quantitative data were used to verify physical improvements of patients .The Visual Analogue Scale for pain (VAS) was used in 9.4% of the studies ,23,24,25The heterogeneity of clinical scores used in the studies did not allow the calculation of definitive quantitative outcomes.n = 15; 62.5%) were evaluated with MINORS. Of these studies, 10 (66.7%) had a low risk of bias, and 5 (33.3%) had a high risk of bias. Non-randomized studies (Nine studies were RCTs. One article (11.1%) had high quality, six articles (66.6%) had moderate quality due to insufficient details about sources of bias, and two articles (22.3%) had low quality due to inadequate information about the double-blinding process and sources of bias.Remote virtual rehabilitation aroused growing interest in the last decades, and its role has gained importance following the recent spread of the COVID19 pandemic. The advantages of VR, AR, gamification, and telerehabilitation have been already demonstrated in several medical fields ,36, but In this review, we searched the literature for studies using remote technologies for orthopedic rehabilitation and analyzed the studies’ quality, type and field of rehabilitation, patients’ characteristics, and outcomes to describe the state of the art of VR, AR, gamification, and telerehabilitation for orthopedic rehabilitation. Available studies about remote virtual rehabilitation mainly concern telerehabilitation and, to a lesser extent, VR, AR, and gamification. The reason is that gamification has been introduced only recently and only few studies have investigated it so far. The first use of VR and AR dates back to 1998, when the improved image visualization was supposed to be applied for diagnostic purposes . ProgresVirtual technologies have been largely evaluated for remote rehabilitation following knee and hip arthroplasty. Studies usually included patients between 40 and 60 years of age, who mostly had a university degree. Age and social context influence adaptability to technology. For elderly patients, it is challenging to approach technology, while younger patients are predisposed to it . TherefoThe analysis of qualitative and quantitative outcomes showed increased patient self-esteem and a consolidated relationship with the physiotherapist, as well as good clinical outcomes . The effOrthopedic remote rehabilitation leads to reduced costs for the national health system. As already proven in other medical fields , decreasNew technologies offer promise for the growing demand of orthopedic rehabilitation, but barriers and issues need to be overcome in the field. Elderly patients represent a substantial part of orthopedic patients. However, the spreading of VR, AR, gamification, and telerehabilitation is limited among patients of advanced age. This category of patients is not prone to new technologies and showed low adaptability to them. The main challenge is to improve these technologies to be accessible and suitable for this population. Their technology should be targeted, and the experience should be simplified to engage the patient. By employing machine learning, exercises can be tailored to patient’s needs and ability. Moreover, an intuitive interface can facilitate the use of virtual technologies.Real-time monitoring of patients’ physiotherapy is another challenge. The need to analyze user activity as it is happening can be useful to prevent pitfalls during training. It can be bypassed by programmed visual-optic feedbacks for specific tasks. Future developments should focus on adequate data storage systems and real-time analysis of continuous updated information, to provide immediate feedback to patients. Those systems should also guarantee privacy protection. There is huge potential for remote virtual rehabilitation as shown by data reported by available studies. It is recommended that these technologies should be further improved and their fields of application should be expanded as they allow the delivery of high-quality care at reduced costs.Future studies should establish the areas of physiotherapy that will benefit most from this technology. New digitally enabled technological solutions should be searched to underpin transformative health innovations that can have a direct benefit to patients’ rehabilitation.The main limitation of this review is the heterogeneity of included studies that prevented a meta-analysis of their results. There were no standard procedures or protocols, and different equipment were used. Outcomes measurement methods differed between studies, and many data were qualitative rather than quantitative. Only nine RCTs and 15 non-randomized studies were analyzed. Nevertheless, RCTs were of high or moderate quality and the majority of the non-randomized studies had a low risk of bias. The literature lacks data regarding patient’s perception of new technology and adherence to therapy. Future research needs to develop specific and objective methods to evaluate the clinical quality of new technologies. To our knowledge, this is the first study providing an overview of remote virtual techniques for orthopedic rehabilitation. This study provides an overview of the field, highlighting the benefits of these methods. At the same time, this review underlines the need for future research to definitively demonstrate advantages of VR, AR, gamification, and telerehabilitation compared to face-to face orthopedic rehabilitation. This review evaluated literature about remote virtual technologies for orthopedic rehabilitation. Only nine RCTs and 15 non-randomized studies were available in literature, but their quality was high or moderate and the risk of bias was low. Heterogeneity of included studies prevented a meta-analysis of their results. There were no standard procedures or protocols, and different equipment and outcomes measurement methods were employed between studies. Age and social context influence adaptability to technology, and it can modify compliance to treatment and outcomes. A good relationship between patient and physiotherapist is essential for treatment compliance, and new technologies are useful to maintain clinical interactions remotely. Remote virtual technologies allow the delivery of high-quality care at reduced costs. This is a necessity given the growing demand for orthopedic rehabilitation and increasing costs related to it. Future studies need to develop specific and objective methods to evaluate the clinical quality of new technologies and definitively demonstrate advantages of VR, AR, gamification, and telerehabilitation compared to face-to face orthopedic rehabilitation.


Conventional spinal navigation solutions have been criticized for having a negative impact on time in the operating room and workflow. AR navigation could potentially alleviate some of these concerns while retaining the benefits of navigated spine surgery. The objective of this study is to summarize the current evidence for using augmented reality (AR) navigation in spine surgery.We performed a systematic review to explore the current evidence for using AR navigation in spine surgery. PubMed and Web of Science were searched from database inception to November 27, 2020, for data on the AR navigation solutions; the reported efficacy of the systems; and their impact on workflow, radiation, and cost-benefit relationships.In this systematic review, 28 studies were included in the final analysis. The main findings were superior workflow and non-inferior accuracy when comparing AR to free-hand (FH) or conventional surgical navigation techniques. A limited number of studies indicated decreased use of radiation. There were no studies reporting mortality, morbidity, or cost-benefit relationships.AR provides a meaningful addition to FH surgery and traditional navigation methods for spine surgery. However, the current evidence base is limited and prospective studies on clinical outcomes and cost-benefit relationships are needed. Compared to conventional free-hand (FH) surgical techniques, computer-assisted surgery (CAS) has been shown to improve pedicle screw placement accuracy and is gaining use in spine surgery . DespiteAn ideal CAS solution allows for the visualization of the anatomy without obscuring the surgical field or distracting the surgeon. In augmented reality (AR) navigation solutions, the real environment and virtual information is presented in the same field of view . The AR Current research on AR navigation is at an early stage . One of This study aims to present a systematic review of the current state of AR navigation in spine surgery. We describe the currently available AR navigation interfaces and patient tracking solutions, and summarize the reported accuracies and impact on clinical outcomes, as well as the impact on workflow, radiation, and cost-benefit relationships. Focusing on clinically relevant publications, only studies on patients, cadavers, or cadaveric vertebral models are included.A systematic search was performed in two databases, “PubMed” and “Web of Science.” All studies written in English from database inception until 27th of November 2020 were included. A combination of the words and phrases , and  surgery) or (pedicle screw), was used. Each included study was screened for additional cited and relevant studies to be included in the systematic review. Based on title and abstract, an eligibility screening was performed by two authors. Next, a selection of eligible studies was performed by analyzing full texts. The review followed the Preferred Reporting Items on Systematic Reviews and Meta-analysis (PRISMA) guidelines .Inclusion criteria were (1) studies in English; (2) minimum evidence level V using Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence; (3) AR was used in spine surgery on patients, cadavers, or cadaveric vertebral models; and (4) surgical outcome was reported. Exclusion criteria were (1) review articles or meeting abstracts; (2) articles lacking an available full text; (3) AR used for surgery other than spinal, or solely for biopsies or non-surgical injections; (4) proof-of-concept studies or case-reports reporting single attempts; and (5) studies reporting only qualitative feedback from surgeons.Data extraction consisted of author and year of study, type of study subjects, AR interface type, patient tracking solution, and the main findings. Main findings were further sub-divided into accuracy assessment, radiation dose, and cost-benefit analyses. The quality of the available evidence was graded according to the GRADE criteria .A total of 28 studies were included, as shown in Fig. Four main types of AR user interfaces were identified among the included studies. The two most common were monitor-based  and head-mounted displays HMD-AR, 12 studies). Monitor-AR typically consisted of video cameras, imbedded in the C-arm, aimed at the surgical field and a separate monitor displaying the video feed with AR overlay  were provided in a majority of Monitor-, Projector-, and HMD-AR studies. However, there was no consensus on 1D, 2D, or 3D translational measurements or the anatomical plane when reporting 1D or 2D measurements. No study using Microscope-AR provided technical accuracy. Target registration error (TRE), describing the calculated reliability, or quality, of the patient registration in the navigation software, was reported instead. Since TRE is only one out of many parts contributing to the final technical accuracy, a direct comparison is not possible.Patient registration was performed in three principal ways. Ten studies used intraoperative cone beam computed tomography (CBCT), with simultaneous patient position registration, to align radiological imaging with the patient in the operating room (OR) –22, 38. Overall, four different patient tracking technologies were used. All technologies relied on optical tracking, where optical or infrared cameras were used. Ten studies used optical markers attached to the patients’ skin, surrounding the surgical field –22, 38. p < 0.05). The same authors used Gertzbein grading to compare AR-navigated and FH pedicle screw accuracies without fluoroscopic guidance in a cadaveric setup where AR had a superior accuracy  [p = 0.50) but in secondary reported outcomes the trend was towards increased accuracy using AR. Although no power analysis was provided, the authors discussed that the study could have been underpowered. Comparing HMD-AR to FH with fluoroscopy, Urakov et al. observed fewer major breaches in the FH group (HMD-AR: 36.8% vs. FH: 0% major breaches) [p = 0.106). Dennler et al. compared HMD-AR to FH in two groups of surgeons: novice or experienced spine surgeons [p = 0.044).Seven studies compared AR to FH with or without fluoroscopy for pedicle screw placement , 38, 42. < 0.05) . Peh et reaches) . No signsurgeons . They fop < 0.05 for all). Wanivenhaus et al. evaluated the benefit of AR for manual rod bending [p = 0.012). Rod length was also significantly more often correct with AR .There were three studies comparing AR navigation to FH, with or without fluoroscopy, for spinal procedures other than pedicle screw placement. In a randomized controlled trial, Auloge et al. compared the accuracy of the pedicle cannulation phase in percutaneous vertebroplasty between two groups of 10 patients each, one using AR and the other FH with fluoroscopy . They fo bending . When cop = 0.85) or angular errors .Only one study compared AR navigation to other modalities of navigated spine surgery. Müller et al. used an HMD-AR device to place pedicle screws . The conThree studies reported shorter and one longer operating times when using AR compared to FH with or without fluoroscopy , 45, 46.All studies reporting on radiation doses used either intraoperative CT or intraoperative CBCT for patient registration Table . No stud2 vs. FH: 367.8 ± 184.7 mGy cm2, p = 0.025) and fluoroscopy time  [One study compared AR navigation with CBCT patient registration to FH with fluoroscopy, and found that AR navigation resulted in significantly lower dose-area product  and 15.8 ± 1.8 mSv (thoracolumbar) –13, 17. No included study provided cost-benefit analyses of using AR navigation or discussed costs and benefits in quantitative terms.The use of AR navigation in spine surgery represents a meaningful improvement over existing CAS technologies concerning workflow and ease-of-use and is favorable to FH surgery in terms of accuracy and radiation exposure. AR systems have demonstrated a high accuracy compared to FH surgery in several clinical studies. Notably, all studies involving pedicle screw placement accuracy that reported favorable results for AR relied on Monitor-AR. HMD-AR was either comparable or inferior to FH surgery for pedicle screw placement. This may be explained by the fact that HMD systems are comparatively newer and have one additional tracked object (the HMD itself), thereby increasing the complexity and potential for errors. Another explanation could be that all Monitor-AR included in this systematic review relies on intraoperative CBCT and skin markers for patient registration and tracking, while most HMD-AR relies on manual registration and direct patient surface tracking. When using manual registration and direct surface tracking, the AR image is manually adjusted to match the reality thereby inducing a potential registration error. Intraoperative imaging in combination with optical markers or a DRF, however, allows for an accurate automatic co-registration , 10. NonAn ideal navigation system for spine surgery should provide a clear interface highlighting only what is important and an unobtrusive patient tracking with high fault-tolerance. Proponents of HMD-AR may argue that it will represent the optimal user experience once the technology is matured, provided it reaches an acceptable accuracy. If the HMD device is unobtrusive and lightweight and offers a wide field of view, having the AR overlay directly in the surgeon’s view could be an advantage. However, HMD may increase the risk for inattentional blindness compared to monitors . NonetheIn this systematic review, the impact of AR navigation on radiation exposure for both patients and staff were favorable compared to FH. Given that AR principally concerns presentation of imaging data, the radiation exposure is expected to be comparable to other CAS solutions. However, improved workflow may reduce staff exposure, while increased accuracy may reduce the need for additional imaging.Notably, no study provided any cost-benefit analyses of using AR navigation. However, the financial benefits of navigation were presented in a recent review indicating that using navigation results in “buying-back” the investment in the long term . There iAn ideal spinal navigation system should provide a time-efficient setup and registration, be easy to use, and allow visualization of the anatomy without distracting the surgeon or obscuring the surgical field , 26. TheThe obtained technical accuracy by AR is already relatively high. The challenge is to achieve maximal accuracy also in complex cases. By including AR tracking of the surgical tools, a more direct feedback could be achieved . MoreoveTo further improve surgical results, AR navigation could be combined with sensing technologies such as impedance probes or optical probes relying on diffuse reflectance spectroscopy (DRS) , 39. TheArguably, it is only a matter of time until technological achievements transferred to spine surgery will have the upper hand in terms of accuracy in identifying static anatomical landmarks and eventually also dynamic or moving surgical targets. The boundaries between what can and what cannot be done with computer assistance, robotics, and AI in surgery will primarily be defined by medico-legal concerns rather than technological. However, for a foreseeable time, the surgical handicraft needed for decompression and microneurosurgical handling of intrathecal nervous system tissues will be reserved for the surgeon. Nonetheless, AR visualization may provide the surgeon with valuable assistance in the performance of these delicate maneuvers.clinicaltrials.gov, meaning the ability to objectively evaluate publication bias is currently lacking.AR in spine surgery is a relatively new concept reflected in the limited number of publications. Most included studies were non-controlled or non-randomized, which could introduce a potential bias in the study outcomes and conclusions. Only one RCT was identified in our systematic review. Only one study was publicly registered before beginning the trial and no additional studies could be found by the authors of this review on AR provides a meaningful addition to FH surgery and traditional navigation methods for spine surgery. By enhancing the surgical field with radiological guidance information, the surgeon’s attention is kept on the surgical field. In this systematic review, superior workflow and non-inferior accuracy were the main findings when comparing AR to FH or conventional navigation techniques. A limited number of studies indicated decreased radiation dose for both patients and staff.Future developmental efforts should be focused on further improving the AR system setups regarding workflow optimization and choice of the method to present virtual information. Future studies on the impact on clinical outcomes such as patient mortality, morbidity, and complications are required.


S)-1,1′-bianaphthalene-2,2′-diamine derivatives possessing additional chiral and fluorophore substituents. The Compounds thus obtained were tested as potential detectors of seven amino alcohols, and some of them were found to be able to recognize individual enantiomers of certain amino alcohols by specific changes of their emission spectra in the presence of these analytes. A pronounced dependence of the detecting abilities on the nature of the substituents in the (S)-BINAM derivatives was observed.Pd(0)-catalyzed amination was employed for the synthesis of a new family of ( The application of fluorescent methods for the recognition of individual enantiomers of optically active molecules has gained much attention in the recent decade and successfully competes with other spectroscopic techniques like spectrophotometric (or colorimetric) methods ,2 or meaBoth 1,1′-binaphthalene and chiral 2,2′-binaphthol (BINOL) were shown for the first time to change their fluorescence spectra in the presence of chiral amines ,5. Soon N-Boc-alanine and N-Boc-phenylalanine + 635.3386, found 635.3362.Compound 8. A two-neck flask equipped with a magnetic stirrer and reflux condenser, flushed with dry argon, was charged with Compound 2 , Pd(dba)2 , BINAP , and absolute dioxane (10 mL). After stirring for 2 min, amine 4  and tBuONa  were added and the reaction mixture was refluxed for 15 h. After the reaction was over, the residue was filtered, washed with dichloromethane (3 × 5 mL), combined filtrates were evaporated in vacuo, and the residue was chromatographed on silica gel using a sequence of eluents: CH2Cl2, CH2Cl2–MeOH 200:1–50:1. Target Compound 8 was obtained with CH2Cl2–MeOH 100:1 eluent. Yield 706 mg (85%), light-beige crystalline Compound, m. p. 114–116 °C. 1H-NMR : δ 1.46 , 1.65–1.75 , 1.76–1.90 , 1.90–2.01 , 2.91 br. s + (2.97–3.12) br. m + 3.23 br. s + 3.33 br. s + 3.45 br. s , 3.99 br. s + 4.14 br. s , 5.55 , 6.19 ), 6.27 ), 6.36 ), 6.99 ), 7.14 ), 7.13–7.18 ), 7.27–7.32 ), 7.73 ), 7.82–7.87 ), two NH protons were not assigned. 13C-NMR : δ 22.8 + 23.9 (2CH2), 28.4 (6CH3), 29.3 (2CH2), 46.5 + 46.9 + 49.4 br. (4CH2N), 55.0 + 56.4 (2CHN), 79.6 + 79.9 (2C(t-Bu)), 104.1 br. (2CH(Ph)), 106.7 br. + 107.1 br. (2CH(Ph)), 109.0 br. (2CH(Ph)), 116.1 br. (2C(Nf)), 118.3 (2CH(Nf)), 123.1 (2CH(Nf)), 124.5 (2CH(Nf)), 126.8 (2CH(Nf)), 128.1 (2CH(Nf)), 129.1 (2CH(Ph)), 129.2 (2C(Nf)), 129.7 (2CH(Nf)), 134.0 (2C(Nf)), 140.6 br. (2NC(Ar)), 143.5 br. (2NC(Ar)), 149.1 br. (2NC(Ar)), 154.7 br. + 156.0 (2CO). MALDI-TOF calcd for C52H61N6O4 [M + H]+ 833.4754, found 833.4817.Compound 9. A two-neck flask equipped with a magnetic stirrer and reflux condenser, flushed with dry argon, was charged with Compound 2 , Pd(dba)2 , BINAP , and absolute dioxane (2 mL). After stirring for 2 min, amine 5  and tBuONa  were added and the reaction mixture was refluxed for 15 h. After the reaction was over, the residue was filtered, washed with dichloromethane (3 × 3 mL), combined filtrates were evaporated in vacuo, and the residue was chromatographed on silica gel using a sequence of eluents: CH2Cl2, CH2Cl2–MeOH 200:1–5:1. Target Compound 9 was obtained with CH2Cl2 eluent. Yield 129 mg (79%), yellow glassy Compound. 1H-NMR : δ 1.14 , 1.65–1.88 , 2.21 , 3.48 , 3.67–3.74 , 3.75–3.80 , 4.44 , 4.51 , 5.57 , 6.23–6.28 ), 6.34 ), 7.19 ), 7.16–7.21 , H(BiNp)), 7.22–7.28 , H(BiNp)), 7.29–7.35 ), 7.76 ), 7.86 ), 7.88 ). 13C-NMR : δ 21.8 (2CH2), 30.0 (2CH2), 31.7 (2CH2), 59.9 (2CHN), 71.0 (2CH2O), 85.0 (2CHO), 104.7 (2CH(Ph)), 107.3 (2CH(Ph)), 109.3 (2CH(Ph)), 118.4 (2CH(BiNp)), 119.9 (2C(BiNp)), 123.4 (2CH(BiNp)), 124.5 (2CH(BiNp)), 126.9 (2CH(Ph)), 127.5 (2CH(BiNp)), 127.6 (4CH(Ph)), 128.1 (2CH(BiNp)), 128.3 (4CH(Ph)), 129.2 (2CH(Ph)), 129.3 (2C(BiNp)), 129.8 (2CH(BiNp)), 134.0 (2C(BiNp)), 138.4 (2C(Ph)), 140.5 (2NC(Ar)), 143.5 (2NC(Ar)), 148.6 (2NC(Ar)). MALDI-TOF calcd for C56H55N4O2 [M + H]+ 815.4325, found: 815.4369.Compound 10. A two-neck flask equipped with a magnetic stirrer and reflux condenser, flushed with dry argon, was charged with Compound 2 , Pd(dba)2 , BINAP , and absolute dioxane (10 mL). After stirring for 2 min, amine 6  and tBuONa  were added and the reaction mixture was refluxed for 15 h. After the reaction was over, the residue was filtered, washed with dichloromethane (3 × 5 mL), combined filtrates were evaporated in vacuo, and the residue was chromatographed on silica gel using a sequence of eluents: CH2Cl2, CH2Cl2–MeOH 200:1–50:1. Target Compound 10 was obtained with CH2Cl2–MeOH 100:1 eluent. Yield 688 mg (89%), light-beige crystalline Compound, m. p. 66–68 °C. 1H-NMR : δ 3.20 , 3.39 , 3.57 , 3.93 , 5.63 , 6.24–6.29 ), 6.43 ), 7.04 ), 7.20 ), 7.19–7.23 ), 7.32–7.36 ), 7.78 ), 7.89 ), 7.91 ). 13C-NMR : δ 43.3 (2CH2N), 58.6 (2CH3), 70.8 (2CH2O), 104.4 (2CH(Ph)), 107.3 (2CH(Ph)), 109.4 (2CH(Ph)), 116.2 (2CH(BiNp)), 118.3 (2CH(BiNp)), 123.2 (2CH(BiNp)), 124.4 (2CH(BiNp)), 126.8 (2CH(BiNp)), 128.0 (2CH(BiNp)), 129.1 (2CH(Ph)), 129.2 (2C(BiNp)), 129.8 (2CH(BiNp)), 133.9 (2C(BiNp)), 140.4 (2NC(Ar)), 143.5 (2NC(Ar)), 149.1 (2NC(Ar)). MALDI-TOF calcd for C38H39N4O2 [M + H]+ 583.3073, found: 583.3033.Compound 14. A one-neck flask equipped with a magnetic stirrer was charged with Compound 7 , acetonitrile (2 mL), dansyl chloride 11 , K2CO3 , and the reaction mixture was stirred for 8 h at room temperature. The residue was filtered, washed with dichloromethane (3 × 5 ml), and the combined organic fractions were evaporated in vacuo. The target Compound 14 was obtained as a yellow crystalline powder. Yield 219 mg (98%), m.p. 140–142°C (decomp.). 1H-NMR : δ 1.61–1.70 , 1.75–1.92 , 2.88 , 3.58–3.70 , 3.70–3.76 , 3.83–3.89 , 5.44 , 6.70 ), 6.72 ), 6.80 ), 7.01 ), 7.04 ), 7.12 ), 7.15–7.22 ), 7.29–7.37 ), 7.41 ), 7.77 ), 7.85 ), 8.08–8.13 ), 8.54 ). 13C-NMR : δ 25.3 (2CH2), 29.1 (2CH2), 45.3 (4CH3), 54.0 (2CH2N), 67.9 (2CH2O), 76.4 (2CHO), 115.0 (2CH(Ar)), 116.4 (2C(Np)), 117.3 (2CH(Ar)), 119.0 (2CH(Ar)), 119.6 (2CH(Ar)), 119.9 (2CH(Ar)), 122.5 (2CH(Ar)), 123.0 (2CH(Ar)), 123.6 (2CH(Ar)), 124.2 (2CH(Ar)), 127.0 (2CH(Ar)), 127.7 (2CH(Ar)), 128.1 (2CH(Ar)), 129.3 (2C(Np)), 129.4 (2CH(Ar)), 129.5 (2CH(Ar)), 129.7 (2C(Np)), 130.1 (2C(Np)), 130.3 (2CH(Ar)), 130.7 (2CH(Ar)), 133.5 (2C(Np)), 134.1 (2C(Np)), 139.4 (2NC(Ar)), 140.0 (2NC(Ar)), 142.8 (2NC(Ar)), 151.3 ). MALDI-TOF calcd for C66H65N6O6S2 [M + H]+ 1101.4407, found: 1101.4346.Compound 15. A one-neck flask equipped with a magnetic stirrer was charged with Compound 7 , acetonitrile (1 mL), 4-bromo-7-methoxycoumarin 12 , and K2CO3 , and the reaction mixture was stirred for 8 h at 50 °C. The residue was filtered, washed with dichloromethane (3 × 5 mL), and the combined organic fractions were evaporated in vacuo. The target Compound 15 was obtained as a brownish viscous oil. Yield 149 mg (98%). 1H-NMR : δ 1.48 , 1.78–1.89 , 1.92–2.00 , 3.25 , 3.56 , 3.66–3.72 , 3.77–3.83 , 3.82 , 4.13 , 4.65 , 5.48 , 6.07 , 6.14 ), 6.20 ), 6.32 ), 6.77–6.81 ), 6.96 ), 7.01 ), 7.12–7.16 ), 7.21–7.25 ), 7.43 ), 7.57 ), 7.73 ), 7.75 ). 13C-NMR : δ 25.4 (2CH2), 29.1 (2CH2), 51.3 (2CH2N), 55.0 (2CoumCH2N), 55.6 (2CH3O), 67.9 (2CH2O), 77.9 (2CHO), 104.0 (2CH(Ar)), 106.3 (2CH(Ar)), 109.0 (2CH(Ar)), 109.2 (2CH(Ar)), 110.9 ), 111.4 ), 116.5 (2C(BiNp)), 118.5 ), 120.1 (2CH(Ar)), 123.1 (2CH(Ar)), 124.1 (2CH(Ar)), 124.2 (2CH(Ar)), 126.6 (2CH(Ar)), 128.0 (2CH(Ar)), 128.9 (2CH(Ar)), 129.1 (2C(BiNp)), 129.8 (2CH(Ar)), 133.7 (2C(Ar)), 140.4 (2C(Ar)), 143.7 (2NC(Ar)), 148.5 (2NC(Ar)), 151.6 (2NC(Ar)), 155.4 (2CO), 161.2 (2CO), 162.4 (2CO). MALDI-TOF calcd for C64H59N4O8 [M + H]+ 1011.4333, found: 1011.4297.Compound 16. A two-neck flask equipped with a magnetic stirrer and reflux condenser, flushed with dry argon, was charged with Compound 7 , Pd(dba)2 , DavePhos , and absolute dioxane (2 mL). After stirring for 2 min, 6-bromoquinoline 12  and tBuONa  were added and the reaction mixture was refluxed for 15 h. After the reaction was over the residue was filtered, washed with dichloromethane (3 × 5 mL), the combined filtrates were evaporated in vacuo, and the residue was chromatographed on silica gel using a sequence of eluents: CH2Cl2, CH2Cl2–MeOH 200:1–100:1. Target Compound 16 was obtained with CH2Cl2–MeOH 100:1 eluent. Yield 77 mg (58%), beige crystalline Compound, m. p. 121–124 °C (decomp.). 1H-NMR : δ 1.50 , 1.77–1.98 , 3.71 , 3.79–3.87 , 4.17 , 5.59 , 6.65 ), 6.73 ), 6.78 ), 7.08 ), 7.09 ), 7.18 ), 7.23 ), 7.25–7.31 , H3, H3′(Quin)), 7.40 ), 7.70 ), 7.81 ), 7.85 ), 7.91 ), 7.95 ), 8.69 ). 13C-NMR : δ 25.6 (2CH2), 29.7 (2CH2), 56.8 (2CH2N), 67.9 (2CH2O), 76.6 (2CHO), 112.6 (2CH(Ar)), 114.2 (2CH(Ar)), 114.3 (2CH(Ar)), 116.7 (2C(Ar)), 116.8 (2CH(Ar)), 118.0 (2CH(Ar)), 121.2 (2CH(Ar)), 123.5 (2CH(Ar)), 124.4 (2CH(Ar)), 125.0 (2CH(Ar)), 127.0 (2CH(Ar)), 128.1 (2CH(Ar)), 129.3 (2CH(Ar)), 129.4 (4C(Ar)), 129.5 (2CH(Ar)), 130.1 (2CH(Ar)), 133.8 (2C(Ar)), 134.8 (2CH(Ar)), 139.8 (2C(Ar)), 143.7 (2C(Ar)), 143.8 (2C(Ar)), 146.2 (2C(Ar)), 147.2 (2CH(Ar)), 148.6 (2C(Ar)). MALDI-TOF calcd for C60H53N6O2 [M + H]+ 889.4230, found: 889.4157.Compound 17. A one-neck flask equipped with a magnetic stirrer was charged with Compound 8 , acetonitrile (2 mL), dansyl chloride 11 , and K2CO3 , and the reaction mixture was stirred for 8 h at room temperature. The residue was filtered, washed with dichloromethane (3 × 5 mL), and the combined organic fractions were evaporated in vacuo. The target Compound 17 was obtained as a yellow crystalline powder. Yield 257 mg (99%), m.p. 152–154 °C (decomp.). 1H-NMR : δ 1.10 + 1.32 , 1.70–1.83 , 2.07 + 2.16 , 2.86 , (3.20–3.25) m + 3.30 br. s , (3.50–3.58) m + 3.63 br. s + (3.65–3.79) , 5.44 + 5.46 , (6.61–6.75) m + 6.80 d (3J = 7.8 Hz) + 6.92 br. s ), 6.95–7.12 ), 7.15–7.23 ), 7.27–7.34 ), 7.35–7.43 ), 7.80–7.87 ), 7.98  + 8.05  ), 8.51  + 8.53  ). 13C-NMR : δ 22.3 + 23.3 (2CH2), 27.4 + 28.1 +28.3 (2CH2 + 6CH3(t-Bu)), 45.3 (4CH3N), 46.3 + 46.9 (2CH2N), 50.2 + 51.3 (2CH2N), 55.2 (2CHN), 78.9 + 79.2 (2C(t-Bu)), 115.0 (2CH(Ar)), 116.1 (2C(biNp)), 117.0 br. + 117.4 br. (2CH(Ar)), 119.0 br. + 119.2 br. + 119.6 + 119.8 + 120.3 br. (6CH(Ar)), 121.8 br. + 122.3 br. (2CH(Ar)), 123.0 (2CH(Ar)), 123.5 br. + 123.6 br. (2CH(Ar)), 124.2 (2CH(Ar)), 127.1 br. (2CH(Ar)), 127.6 + 127.7 (2CH(Ar)), 128.1 (2CH(Ar)), 129.4 br. (4CH(Ar)), 129.7 (2C(Nf)), 130.1 (2C(Nf)), 130.3 + 130.4 (2CH(Ar)), 130.6 (2C(Nf)), 130.8 (2CH(Ar)), 133.5 (2C(Nf)), 133.9 + 134.1 (2C(Nf)), 139.3 + 139.4 + 139.5 + 139.7 (4NC(Ar)), 142.8 br. (2NC(Ar)), 151.3 + 151.4 ), 154.0 + 154.2 (2CO). MALDI-TOF calcd for C76H83N8O8S2 [M + H]+ 1299.5775, found: 1299.5712.Compound 18. A one-neck flask equipped with a magnetic stirrer was charged with Compound 8 , acetonitrile (1 mL), 4-bromo-7-methoxycoumarin 12 , and K2CO3 , and the reaction mixture was stirred for 8 h at 50 °C. The residue was filtered, washed with dichloromethane (3 × 5 mL), combined organic fractions were evaporated in vacuo, and the residue was chromatographed on silica gel using a sequence of eluents: CH2Cl2, CH2Cl2–MeOH 200:1–50:1. Target Compound 18 was obtained with CH2Cl2–MeOH 100:1 eluent. Yield 130 mg (71%), yellow glassy Compound. 1H-NMR : δ 1.28 , 1.36 , 1.75–1.97 , 3.05–3.20 , 3.27 , 3.38 , 3.48–3.60 , 3.83 , 4.07 + 4. 14 , 4.43 + 4.48 , 5.34 + 5.50 + 5.58 , 6.00 + 6.04 ), 6.24–6.41 ), 6.73–6.84 ), 6.95–7.04 , H3, H3′(BiNp)), 7.06–7.25 ), 7.31–7.50 , H5, H5′(Coum)), 7.63–7.69 ), 7.73 ). 13C-NMR : δ 22.6 + 23.5 (2CH2), 28.3 (6CH3), 28.6 + 28.9 (2CH2), 46.2 + 46.7 (2CH2N), 51.6 + 53.3 + 53.8 + 55.3 , 55.6 (2CH3O), 79.1 + 79.9 (2C(t-Bu)), 100.8 + 101.1 ), 104.0–104.5 м. (4C), 106.4 (2C), 109.4 (2C), 111.1 + 111.3 (2C), 112.0 + 112.2 (2C), 117.1 (2C), 118.7 + 119.0 (2C), 123.2 (2C), 133.8 + 124.1 + 124.3 (4C), 126.6 (2C), 128.0 (2C), 128.8 + 128.9 + 129.0 (4C), 129.3 (2C), 129.8 (2C), 133.8 (2C), 140.4 (2C), 144.0 + 144.2 (2C), 148.1 + 148.5 (2C), 150.9 + 151.1 (2C), 151.5 + 151.6 (2C), 154.4 + 155.4 (2CO(t-Bu)), 161.1 + 162.5 ). MALDI-TOF calcd for C74H77N6O10 [M + H]+ 1209.5701, found: 1209.5765.Compound 19. A two-neck flask equipped with a magnetic stirrer and reflux condenser, flushed with dry argon, was charged with Compound 8 , Pd(dba)2 , DavePhos , and absolute dioxane (2 mL). After stirring for 2 min, 6-bromoquinoline 12  and tBuONa  were added and the reaction mixture was refluxed for 15 h. After the reaction was over, the residue was filtered, washed with dichloromethane (3 × 5 mL), combined filtrates were evaporated in vacuo, and the residue was chromatographed on silica gel using a sequence of eluents: CH2Cl2, CH2Cl2–MeOH 200:1–100:1. Target Compound 19 was obtained with CH2Cl2–MeOH 100:1 eluent. Yield 68 mg (41%), yellow viscous oil. 1H-NMR : δ 1.38 , 1.45 , 1.66–1.95 , 3.25 br. s + 3.32–3.40 br. m , 3.40–3.46 br. m + 3.52 br. s , 4.02 d (2J = 12.4 Hz) + 4.13 br. d (2J = 12.4 Hz) , 4.21 , 5.53 + 5.65 + 5.67 , 6.60–6.65 m + 6.71 d (3J = 8.0 Hz) ), 6.67 + 6.85 ), 7.05–7.19 m +7.54 br. s , H5, H5′(Quin), H3, H3′, H6, H6′(Np)), 7.24–7.28 m + 7.28–7.33 br. m 7.36–7.41 br. m , H3, H3′(Quin)), 7.62–7.70 br. m + 7.80 d (3J = 8.3 Hz), 7.80–7.85 br. m ), 7.88–7.98 br. m + 8.06 br. d (3Jobs = 8.0 Hz) ), 8.69 ). 13C-NMR : δ 22.6 + 23.5 (2CH2), 28.4 + 28.6 , 46.4 + 46.7 (2CH2N), 54.3 + 54.5 (2CH2N), 55.3 (2CHN), 79.1 + 79.9 (2C(t-Bu)), 112.6 + 113.0 (2CH(Ar)), 114.1 + 114.4 + 114.8 (4CH(Ar)), 116.4 + 116.8 (2C(Ar), 2CH(Ar)), 118.0 + 118.3 (2CH(Ar)), 121.0 + 121.4 (2CH(Ar)), 123.6 (2CH(Ar)), 124.5 + 125.3 (4CH(Ar)), 126.9 + 127.0 (2CH(Ar)), 128.2 (2CH(Ar)), 129.4 + 129.8 (4CH(Ar), 4C(Ar)), 130.3 (2CH(Ar)), 133.8 + 134.7 (2CH(Ar)), 135.9 + 136.1 (2C(Ar)), 139.8 (2C(Ar)), 144.0 (4C(Ar)), 146.5 + 147.6 (2CH(Ar), 2C(Ar)), 149.0 (2C(Ar)), 154.4 + 154.7 (2CO). MALDI-TOF calcd for C70H71N8O4 [M + H]+ 1087.5598, found: 1087.5663.Compound 22. A one-neck flask equipped with a magnetic stirrer was charged with Compound 10 , acetonitrile (1 mL), dansyl chloride 11 , and K2CO3 , and the reaction mixture was stirred for 8 h at room temperature. The residue was filtered, washed with dichloromethane (3 × 5 mL) and the combined organic fractions were evaporated in vacuo. The target Compound 22 was obtained as a brownish crystalline powder. Yield 130 mg (83%), m.p. 120–122 °C. 1H-NMR : δ 2.89 , 3.19 , 3.38 , 3.75 , 5.45 , 6.87 ), 6.71 ), 6.76 ), 7.01 ), 7.02 ), 7.13 ), 7.19 ), 7.20 ), 7.32 ), 7.34 ), 7.42 ), 7.77 ), 7.84 ), 8.10 ), 8.15 ), 8.55 ). 13C-NMR : δ 45.4 (4CH3N), 49.9 (2CH2N), 58.5 (2CH3O), 69.9 (2CH2O), 115.2 (2CH(Ar)), 116.5 (2C(Ar)), 117.4 (2CH(Ar)), 119.0 (2CH(Ar)), 119.7 (2CH(Ar)), 120.1 (2C(Ar)), 122.7 (2CH(Ar)), 123.1 (2CH(Ar)), 123.7 (2CH(Ar)), 124.3 (2CH(Ar)), 127.0 (2CH(Ar)), 127.7 (2CH(Ar)), 128.2 (2CH(Ar)), 129.5 (6CH(Ar)), 130.2 (2C(Ar)), 130.3 (2CH(Ar)), 130.7 (2CH(Ar)), 133.6 (2C(Ar)), 134.3 (2C(Ar)), 139.4 (2NC(Ar)), 140.0 (2NC(Ar)), 143.0 (2NC(Ar)), four quaternary carbon atoms were not assigned. MALDI-TOF calcd for C62H61N6O6S2 [M + H]+ 1049.4094, found: 1049.4030.Compound 23. A one-neck flask equipped with a magnetic stirrer was charged with Compound 10 , acetonitrile (1 mL), 4-bromo-7-methoxycoumarin 12 , and K2CO3 , and the reaction mixture was stirred for 8 h at 50 °C. The residue was filtered, washed with dichloromethane (3 × 5 mL), and the combined organic fractions were evaporated in vacuo. Target Compound 23 was obtained as a brownish crystalline Compound. Yield 141 mg (98%), m.p. 126–128 °C. 1H-NMR : δ 3.28 , 3.48–3.52 , 3.53–3.56 , 3.83 , 4.56 , 5.47 , 6.09 , 6.11 ), 6.20 ), 6.34 ), 6.79 ), 6.82 ), 6.97 ), 7.03 ), 7.15 ), 7.24 ), 7.40 ), 7.57 ), 7.74 ), 7.76 ). 13C-NMR : δ 50.9 (2CH2N), 51.8 (2CH3O), 55.6 (2CH3O), 58.9 (2CoumCH2N), 70.7 (2CH2O), 101.0 (2CH=), 103.8 (2CH(Ar)), 106.2 (2CH(Ar)), 109.0 (2CH(Ar)), 109.3 (2CH(Ar)), 111.4 ), 112.1 (2CH(Ar)), 116.8 (2C(BiNp)), 118.7 (2CH(Ar)), 123.2 (2CH(Ar)), 124.1 (2CH(Ar)), 124.4 (2CH(Ar)), 126.7 (2CH(Ar)), 128.0 (2CH(Ar)), 129.0 (2CH(Ar)), 129.3 (2C(BiNp)), 129.9 (2CH(Ar)), 133.8 (2C(Ar)), 140.4 (2C(Ar)), 143.9 (2NC(Ar)), 148.2 (2NC(Ar)), 151.7 (2NC(Ar)), 155.5 (2CO), 161.2 (2CO), 162.5 (2CO). MALDI-TOF calcd for C60H55N4O8 [M + H]+ 959.4020, found: 959.3957.Compound 24. A one-neck flask equipped with a magnetic stirrer was charged with Compound 10 , acetonitrile (1 mL), 4-bromo-6, 7-dimethoxycoumarin 20 , and K2CO3 , and the reaction mixture was stirred for 8 h at 50 °C. The residue was filtered, washed with dichloromethane (3 × 5 mL), and the combined organic fractions were evaporated in vacuo. Target Compound 24 was obtained as a brownish crystalline Compound. Yield 150 mg (98%), m.p. 131–133 °C. 1H-NMR : δ 3.29 , 3.48–3.52 , 3.53–3.57 , 3.80 , 3.87 , 4.59 , 5.59 , 6.10 , 6.16 ), 6.20 ), 6.38 ), 6.77 ), 6.82 ), 6.96 ), 7.02 ), 7.12 ), 7.20 ), 7.60 ), 7.73 ). 13C-NMR : δ 50.7 (2CH2N), 51.9 (2CH3O), 56.1 (2CH3O), 56.2 (2CH3O), 58.9 (2CoumCH2N), 70.7 (2CH2O), 100.0 (2CH=), 103.8 (2CH(Ar)), 103.9 (2CH(Ar)), 106.1 (2CH(Ar)), 108.7 (2CH(Ar)), 109.6 (2CH(Ar)), 110.2 ), 116.7 (2C(BiNp)), 118.5 (2CH(Ar)), 123.1 (2CH(Ar)), 124.3 (2CH(Ar)), 126.6 (2CH(Ar)), 127.9 (2CH(Ar)), 128.9 (2CH(Ar)), 129.2 (2C(BiNp)), 129.8 (2CH(Ar)), 133.8 (2C(Ar)), 140.2 (2C(Ar)), 143.8 (2NC(Ar)), 145.9 (2NC(Ar)), 148.3 (2NC(Ar)), 149.5 (2CO), 151.4 (2CO), 152.5 (2CO), 161.3 (2CO). MALDI-TOF calcd for C62H59N4O10 [M + H]+ 1019.4231, found: 1019.4285.Compound 25. A two-neck flask equipped with a magnetic stirrer and reflux condenser, flushed with dry argon, was charged with Compound 10 , Pd(dba)2 , DavePhos , and absolute dioxane (2 mL). After stirring for 2 min, 6-bromoquinoline 12  and tBuONa  were added and the reaction mixture was refluxed for 15 h. After the reaction was over, the residue was filtered, washed with dichloromethane (3 × 5 mL), combined filtrates were evaporated in vacuo, and the residue was chromatographed on silica gel using a sequence of eluents: CH2Cl2, CH2Cl2–MeOH 200:1–100:1. Target Compound 25 was obtained with CH2Cl2–MeOH 200:1 eluent. Yield 91 mg (71%), yellow crystalline Compound, m.p. 106–108 °C. 1H-NMR : δ 3.30 , 3.56 , 3.92 , 5.60 , 6.65 ), 6.70. ), 6.76 ), 7.08 ), 7.10 ), 7.16–7.20 ), 7.18 ), 7.25–7.30 , H3, H3′(Quin)), 7.37 ), 7.70 ), 7.81 ), 7.85 ), 7.90 ), 7.94 ), 8.69 ). 13C-NMR : δ 51.8 (2CH2N), 59.0 (2CH2O), 69.4 (2CH2O), 112.3 (2CH(Ar)), 114.0 (2CH(Ar)), 114.2 (2CH(Ar)), 116.6 (2CH(Ar)), 116.8 (2C(Ar)), 118.1 (2CH(Ar)), 121.2 (2CH(Ar)), 123.6 (2CH(Ar)), 124.4 (2CH(Ar)), 124.8 (2CH(Ar)), 127.0 (2CH(Ar)), 128.1 (2CH(Ar)), 129.3 (2CH(Ar)), 129.5 (4C(Ar)), 129.6 (2CH(Ar)), 130.1 (2CH(Ar)), 133.8 (2C(Ar)), 134.7 (2CH(Ar)), 139.8 (2C(Ar)), 143.7 (2C(Ar)), 143.9 (2C(Ar)), 145.8 (2C(Ar)), 147.3 (2CH(Ar)), 148.1 (2C(Ar)). MALDI-TOF calcd for C56H49N6O2 [M + H]+ 837.3917, found: 837.3882.Compound 26. A two-neck flask equipped with a magnetic stirrer and reflux condenser, flushed with dry argon, was charged with Compound 10 , Pd(dba)2 , DavePhos , and absolute dioxane (2 mL). After stirring for 2 min, 6-bromoquinoline 21  and tBuONa  were added and the reaction mixture was refluxed for 15 h. After the reaction was over, the residue was filtered, washed with dichloromethane (3 × 5 mL), combined filtrates were evaporated in vacuo, and the residue was chromatographed on silica gel using a sequence of eluents: CH2Cl2, CH2Cl2–MeOH 500:1–100:1. Target Compound 26 was obtained with CH2Cl2–MeOH 250:1 eluent. Yield 44 mg (39%), yellow viscous oil. 1H-NMR : δ 3.28 , 3.54 , 3.90 , 5.56 , 6.64 ), 6.66–6.70 ), 7.08 ), 7.09 ), 7.17–7.21 ), 7.27–7.31 ), 7.47–7.56 ), 7.63–7.67 ), 7.70 ), 7.82 ), 7.88 ), 8.10 ), 8.64 ). 13C-NMR : δ 51.9 (2CH2N), 59.1 (2CH3O), 69.5 (2CH2O), 113.4 (2CH(Ph)), 114.5 (2CH(Ph)), 116.0 (2CH(Ph)), 117.2 (2C(Ar)), 118.3 (2CH(Ar)), 122.0 (2CH(Ar)), 123.7 (2CH(Ar)), 124.5 (2CH(Ar)), 126.6 (2CH(Ar)), 127.1 (2CH(Ar)), 127.4 (2CH(Ar)), 127.5 (2CH(Ar)), 128.2 (2CH(Ar)), 129.0 (2CH(Ar)), 129.5 (2CH(Ar)), 129.6 (2CH(Ar)), 130.5 (2CH(Ar)), 133.8 (2CH(Ar)), 139.7 (4C(Ar)), 141.6 (4C(Ar)), 144.3 (2CH(Ar)), 147.2 (4C(Ar)). MALDI-TOF calcd for C56H49N6O2 [M + H]+ 837.3917, found: 837.3855.−5 M solution of the corresponding ligand 7, 14–16, 22–26, and an individual enantiomer of the certain amino alcohol  (C = 0.2 M) was added stepwise  into the cuvette. Emission spectra were recorded with each addition. The excitation wavelengths: 310 nm , 340 nm , 320 nm , 330 nm (24), and 350 nm (26), and they corresponded to the absorption maxima of the ligands under investigation.Titrations of the selected Compounds with amino alcohols using the fluorescence spectra were conducted as follows: The spectrofluorometric cuvette (l = 1 cm) was charged with 3 mL of the 10N,N′-di(3-bromophenyl)substituted (S)-BINAM, was accomplished according to a procedure developed by us earlier [1 with a slight excess (2.2 equiv.) of 1,3-dibromobenzene in the presence of Pd(dba)2/Xantphos (4/4.5 mol%) catalyst -catalyzed amination reactions. The first of them was carried out with (S)-tetrahydrofurfuryl amine (3) and resulted in a 90% yield of the target product of diamination 7. This Compound as well as many others were obtained in the individual state by the column chromatography on silica gel. For this reaction and for subsequent syntheses, the Pd(dba)2/rac-BINAP catalytic system was used, which was shown previously to be the most versatile and convenient. The reactions with two other chiral amines 4 and 5 also produced corresponding diaminated products 8 and 9 in high yields; in the latter case, the use of 16 mol% catalyst was inevitable due to steric hindrances in the amine 5. Compounds 7–9 differ by the nature of the donor atoms in the substituents, their reciprocal positions, and steric hindrances. They possess, besides the C2 chiral BINAM moiety, two (Compounds 7 and 8) or four (derivative 9) additional chiral centers, which may enhance their ability to distinguish between two enantiomers of the analyte. Lastly, simple 2-methoxyethylamino substituents were introduced in the diphenyl-BINAM framework in view of employing the only C2 chirality of the diaminobinaphthalene fragment in the perspective detector (synthesis of Compound 10).Compound 7 possessing two tetrahydrofurfurylamino substituents was subjected to modifications with several fluorophore groups (7) to 505 (Compound possessing 6-aminoquinolinyl moieties) or 520 nm (Compound with dansylamide moieties). Additionally, the number of coordination sites increased after the modifications as all fluorophores employed possess additional N or O donor atoms. The reaction with dansyl chloride 11 allowed the didansylated product 14 in almost a quantitative yield, and this process was carried out at room temperature. The introduction of two 7-methoxycoumarin substituents was accomplished at a slightly elevated temperature to ensure full conversion of the starting Compounds, and the target derivative 15 was also isolated in a 98% yield by a simple work-up of the reaction mixture. The reaction with 6-bromoquinoline (13) proceeded under the catalytic conditions, where the application of 16% mol catalyst and 4 equiv. of the bromide was important to facilitate the heteroarylation of two secondary amino groups. More of the electron-donating DavePhos ligand was used instead of BINAP in this coupling. The isolation of the target Compound 16 by column chromatography afforded a 58% yield of the diquinolinyl derivative. At the next step, the Compound e groups . Such mo8 with two N-Boc-substituted pyrrolidine moieties was reacted with dansyl chloride 11 and 4-bromomethyl)-7-methoxycoumarin 12 under similar conditions, giving the corresponding derivatives 17 and 18 in 99% and 71% yields, respectively (13) (4 equiv.) was accomplished under catalytic conditions to produce the desired product 19 in a 41% yield. For all derivatives 17–19, the NMR spectra are quite complicated due to the presence of two N-Boc groups, resulting in four rotamers. The number of the signals substantially increases together with the line broadening of many of them. The influence of the N-Boc group is different for various parts of the molecule, more seriously altering the aliphatic part. The BINAM derivative ectively . It was 9 containing two benzyloxy-substituted cyclopentylamino groups with additional fluorophore groups was impossible due to steric hindrances at the secondary amino groups. Neither the reaction with dansyl chloride, even at an elevated temperature, nor the attempts to introduce the 7-methoxycoumarin fluorophore substituent were successful. Thus, it should be employed in the fluorescence studies as it is. The decoration of the BINAM derivative 10 was introduced in the reactions with five Compounds to ensure the variety of the fluorophore substituents  was more successful (71% yield of 25) than that with the isomeric 3-bromoquinoline (21) (39% yield of 26) because in the latter case, two successive chromatographic purifications were needed to separate the excess of the starting bromide. The necessity of obtaining such isomers in which quinoline groups are attached in a different manner to the BINAM-based framework is due not only to a difference in the spectral properties on 6- and 3-aminoquinolines but also stems from the different positions of the nitrogen atoms in these two derivatives, which may result in the different binding modes of these molecules.The BINAM derivative tituents . While tThe recognition of the optically active molecules by fluorescent detectors is based on the fact that the coordination of the chiral detector with an enantiomer of the chiral analyte leads to a formation of the chiral complex, and the coordination with the opposite enantiomer of the analyte results in another complex. These complexes, being diastereomers, may possess different fluorescence. For the qualitative analysis, the preferable case is the change of the fluorescence in the presence of one enantiomer and the absence of any change or the change with the opposite sign of the fluorescence in the presence of the opposite enantiomer. More interesting, however, and rarer is the shift of the emission maximum upon the addition of the enantiomer. In the majority of cases, the molecular complexes are formed via hydrogen bonds, and π interactions are also possible. −5 M and 0.2 M concentrations of amino alcohols. Selected data are discussed, which show the influence of the ligands’ structures on their sensing properties and only significant data are presented, where the recognition of the enantiomers was possible. Plausible coordination patterns for amino alcohols with our ligands are shown in The investigation of the ability of synthesized Compounds to act as fluorescent enantioselective detectors was carried out using a panel of seven amino alcohols differing by the nature of the substituents . In prin7 possessing two tetrahydrofurfurylamino moieties. The BINAM fragment is characterized by the absorption maximum at 310 nm and emits at 460 nm. The addition of (S)-tert-leucinol resulted in emission quenching while the presence of the (R)-isomer almost did not change the fluorescence spectrum (14) resulted in the changes of the absorption and emission maxima ; however, it made the ligand’s fluorescence less sensitive to the presence of the amino alcohols. Only in the case of the same tert-leucinol can one note small changes with the opposite sign in the emission spectrum in the presence of two enantiomers (The first studied Compound was spectrum . The addntiomers . Such we15) resulted in the absorption at 320 nm and the emission maximum shifted to the shortwave region at 390 nm (S)-leucinol slightly increased the fluorescence intensity while (R)-isomer did not change it at all. Like its dansylated analog 14, 7-methoxycoumarin derivative 15 in other cases showed weak responses to the addition of other amino alcohols, e.g., the two enantiomers of 2-amino-1-propanol only slightly changed its emission intensity - and (R)-leucinol led to emission quenching, but in the case of the (S)-isomer, the second maximum of lower intensity emerged at 415 nm (16 was noted when adding (S)-2-amino-1-propanol (S)-enantiomers of tert-leucinol and 2-amino-1-propanol did not cause this effect with the other ligands tested, and one may assume that this effect could arise from a specific interaction of two fluorophore moieties present in the Compound 16, i.e., BINAM and quinoline fragments. The coordination with these aminoalcohols could promote the rapprochement of the two fluorophores to produce a new emission band. However, this phenomenon needs to be studied specially. The second plausible explanation is the coordination of the amino alcohol with the nitrogen atom of the quinoline moiety causing the hypsochromic shift. Another coordination mode that does not involve the fluorophore group simply leads to fluorescence quenching. (R)-isomer participates only in the second type of coordination due to the different stabilities of the diastereomers of the molecular complexes.The ligand t 415 nm ; thus, ipropanol ; however22 possessing two additional dansyl fluorophore groups was not informative enough as upon the addition of the amino alcohols, the changes in its emission spectrum were tiny. It could hardly recognize the different enantiomers of tert-leucinol (S)-isomer slightly quenched the emission while (R)-isomer did not change it at all. One may assume that two dansyl groups are spacious enough and shield the chiral centers of the ligand, hindering the formation of the molecular complexes of 14 and 22 with amino alcohols. A similar behavior of the dansylated derivatives of chiral cryptands was observed by us earlier [Next, we studied the BINAM derivatives bearing two 2-methoxyethylamino substituents. The Compound leucinol  and 2-phleucinol : In each earlier .10, resulting in the ligands 23 and 24, changed the spectral response of these Compounds to the presence of amino alcohols. In all cases, a certain enhancement of the fluorescence upon the addition of the analytes was observed, though only in one case, in a pair 23/2-amino-1-butanol, was the difference in this increase substantial for the opposite enantiomers (S)-isomer resulted in much more pronounced emission enhancement than that of (R)-isomer. In the case of 24, the difference for the opposite enantiomers of any amino alcohol was less significant -and (R)-leucinol led to an equal emission quenching at this wavelength. Compound t 505 nm . The add26 was efficient enough. The Compound is able to distinguish between the enantiomers of tert-leucinol (S)-tert-leucinol resulted in the increase in the intensity of the fluorescence with a simultaneous hypsochromic shift of the maximum by ca 20 nm. In the presence of (R)-isomer, a similar shift was also observed together with a tiny quenching of the emission.The introduction of the isomeric 3-aminoquinoline fluorophore in the ligand leucinol , valinolleucinol , and 2-aleucinol . The ligS)- and (R)-enantiomers of 2-amino-1-propanol changed the intensity of fluorescence with opposite signs, and with this amino alcohol, the hypsochromic shift was the most prominent (up to 30 nm). In all experiments, except for the titrations with the Compound 26, we observed changes in the intensities of fluorescence. Such behavior is usual in the case when the photoinduced electron transfer (PET) mechanism of fluorescence is applicable [26 were the hypsochromic shifts of the emission maximum noted upon the addition of the amino alcohols, which may imply that in these cases, the photoinduced charge transfer (PCT) mechanism might be considered. This mechanism is well documented for such fluorophore groups like dansyl, coumarin, and quinoline which possess electron-donating and electron-withdrawing sites to achieve the charge transfer in the fluorophore moiety. This mechanism demands that such an interaction with the analyte takes place, which alters this intramolecular charge transfer. In the case of 26, the quinoline nitrogen atom is situated closer to the methoxy group in the substituent and may participate in the binding of the amino alcohol through the H-bond -isomer is very tiny. Thus, we can conclude that the best detector is able to recognize enantiomers of no more than three amino alcohols. It means that even small changes in the nature of the substituents in these analytes  seriously affect the possibility of forming a molecular complex with the detector to promote necessary changes in the fluorescence.The response of the most interesting detector leucinol , 2-phenyleucinol , or 2-amleucinol  as both leucinol  is dubioS)-BINAM-based potential enantioselective fluorescent detectors were synthesized. Pd(0)-catalyzed amination was successfully employed for the introduction of chiral N- and N,O-containing substituents and additional fluorophore groups. This methodology allowed the synthesis of Compounds combining the C2 chirality of the central BINAM structural unit and an additional two or four stereocenters. The introduction of such fluorophore groups like dansyl and aminoquinoline led to emission at larger wavelengths compared to BINAM. In addition, the number of donor N and O atoms able to participate in binding analytes was increased by such modifications. Nine selected Compounds were tested for their ability to act as enantioselective fluorescent detectors of amino alcohols. Compounds 7, 16, 25, and especially 26 were found to recognize the enantiomers of some analytes by specific changes in their emission spectra, and Compounds 15 and 23 also demonstrated a different behavior in the presence of some amino alcohols, but the changes in the spectra of fluorescence were tiny enough. Compound 26 possessing two 3-aminoquinolines is the most versatile as it was shown to recognize enantiomers of tert-leucinol, valinol, and 2-amino-1-propanol. Among the amino alcohols tested, tert-leucinol was most often the analyte that could be detected by the tested Compounds. It may be due to the presence of a bulky tert-butyl group in its structure, as it is well known that stereodiscrimination is favored by bulky substituents in interacting species. Enantiomers of less bulky leucinol could be recognized in fewer cases. As a result of the research, a new family of (


During this 6th Great Extinction, freshwater quality is imperiled by upland terrestrial practices. Phosphorus, a macronutrient critical for life, can be a concerning contaminant when excessively present in waterways due to its stimulation of algal and cyanobacterial blooms, with consequences for ecosystem functioning, water use, and human and animal health. Landscape patterns from residential, industrial and agricultural practices release phosphorus at alarming rates and concentrations threaten watershed communities. In an effort to reconcile the anthropogenic effects of phosphorus pollution, several strategies are available to land managers. These include source reduction, contamination event prevention and interception. A total of 80% of terrestrial plants host mycorrhizae which facilitate increased phosphorus uptake and thus removal from soil and water. This symbiotic relationship between fungi and plants facilitates a several-fold increase in phosphorus uptake. It is surprising how little this relationship has been encouraged to mitigate phosphorus for water quality improvement. This paper explores how facilitating this symbiosis in different landscape and land-use contexts can help reduce the application of fertility amendments, prevent non-point source leaching and erosion, and intercept remineralized phosphorus before it enters surface water ecosystems. This literature survey offers promising insights into how mycorrhizae can aid ecological restoration to reconcile humans’ damage to Earth’s freshwater. We also identify areas where research is needed. Currently, worldwide freshwater health is increasingly threatened by unprecedented human, terrestrial, upland practices ,2,3,4,5 Though the role of fungi in ecosystem processes has long been recognized, mycoremediation is considered an emerging field. Bioremediation technologies, that originally harnessed bacteria to mitigate pollutants, have been a crucial tool in the last 60 years to filter contaminants from wastewater before discharge to surface water. Now, bioremediation involves a much wider group of organisms including fungi. Mycoremediation can serve as a mitigation approach for non-point source pollution that addresses the problem through source reduction, contamination event prevention, and pollutant interception upland of the receiving water body . ResearcPhytoremediation, on the other hand, involves plants that remove various pollutants such as hydrocarbons, alkanes, phenols, polychlorinated solvents, pesticides, chloroacetamides, explosives, trace elements, toxic heavy metals, metalloids and landfill leachates ,19. PhytWhen mycoremediation and phytoremediation are combined, a synergistic symbiosis is facilitated which also includes microbes ,23. In tMycorrhizae fungi are 400 million-year-old ecological engineers whose evolutionary success has been attributed to their ability to expand the rhizosphere of plants, enabling greater uptake of nutrients from surrounding soils . Early rMycorrhizal fungi are keystone mutualists in terrestrial ecosystems  whose ecOf the seven groups of mycorrhizae, the two most common in agricultural and forested lands  are alsoAdditionally, when planting into AMF grasslands, tree and shrub species’ growth and survival is improved by inoculation with ECM specific to the species planned . ECM preThis paper provides an overview of current research on how mycorrhizae and their native hosts can mitigate water quality degradation. In researching the application of mycorrhizae to remediate phosphorus for water quality purposes, we found ample studies investigating mycorrhizal symbioses in crops such as sorghum, wheat, corn, clover  but few Most P enters water bodies as non-point source pollution with overland flow and streambank erosion of legacy P  and fromTypical sources of phosphorus are manure, fertilizer and compost, although P is also naturally present in soil minerals such as apatite . BecauseHence a key challenge is how to raise the efficiency of agriculture to increase the availability of inorganic phosphorus (Pi) soil reserves to crop plants  while alA phosphorus source reduction approach involves meeting sufficiency recommendations based on soil tests ,68. CalcAnother strategy to reduce P fertilizer use, not often considered in soil fertility measurements, is to involve soil structure improvement that would increase organic matter storage and thus P storage which could become available to plants . P sorptPlants invest up to 20% of photosynthate in mycorrhizal symbioses  to obtai2PO4−, HPO42−, and PO43−). This pool is connected to all other compartments: vegetation, organic P, P sorption sites on Fe and Al oxides, and mineral compounds, so called secondary minerals, which form by precipitation of phosphate with Fe, Al, and Ca ions and release phosphate by dissolution. In addition, there is a phosphorus pool associated with primary P minerals (apatite) which releases P slowly and which may also be manipulated by ECM .,91.90,91Mycorrhizospheres and their composition significantly affect the mobilization of both inorganic particulate and organic P into the SRP pool. This depends on both the quality and the concentration of acids released by mycorrhizae . MycorrhThe amount of SRP in the soil solution affects the efficacy of mycorrhizae to enter into symbiosis with the plant ,99. IncrIn comparison to the sum of the other pools, soil solution phosphorus (SRP) can constitute as little as 0.1% of TP ,102,103.Certain agricultural management practices such as avoiding overfertilization, and applying soil microorganisms which enhance P uptake like mycorrhizae fungi can move us toward more efficient P use . Other sThe host plant’s P requirement and level of soil available P will also influence the extent of plant response to mycorrhizae . AMF parSoil solution may not be the only source of P for AMF. The idea that this group of mycorrhizae might be saprotrophic   riparian buffer , that atHowever, drainage class may still enter into any myco-phytoremediation design because prolonged flooding in wetland riparian buffer, remobilizes P adsorbed to soil colloids. In particular, under anaerobic conditions ferric iron is reduced, releasing phosphate that would otherwise be strongly sorbed to feric oxides . It is nIn terms of the water mitigation paradigm, agricultural fields would be targets of source reduction as they are the primary recipients of P. However, in an area where agriculture was practiced for decades, it is likely the soil has sufficient P to be a source itself .High SRP concentrations in agricultural fields are likely to reduce mycorrhizal infections . TherefoConsequently, managing the field for mycorrhizae can reduce the amount of P fertilizer needed to achieve yield goals . This in−1 without yield loss when it followed wheat, an AMF mycorrhizal crop (Triticum sativum); then when followed by radish (Raphanus sativus), a non-mycorrhizal crop. The benefits may be due to better establishment of mycorrhizae–plant associations under the low soil P supply in the early season with increased uptake of P ensuing [Oka  found th ensuing . Applica ensuing  and shouAlthough agriculture can be regarded as a myco-phytoremediation system for legacy P, agricultural practices affect mycorrhizae. The type and timing of tillage has been identified as one such factor. The role of fungi in plant nutrition and soil conservation is compromised when the formation and survival of propagules  are threatened though tillage, disrupting physical and biological properties of soil. Spores serve as “long- term” propagules when host plants are not present, whereas hyphae are the main source of inoculum when plants are present in undisturbed soil. Deep plowing can dilute propagules, reducing plant root inoculations, especially in autumn when hyphae are detached from the host plant. Conservation tillage can protect survivability and inoculation, thereby improving soil aggregation and P uptake .The structure and texture of soils is also an important factor in whether AMF has significant impacts on leaching and erosion. In agriculture, it is important to look at the relationship between fertilization and runoff. AMF significantly reduced nutrient leaching after rainfall events in sandy grassland soils . This reFurthermore, mycorrhizae can intercept P in soil solution before it leaves the root zone with deep percolation. In contrast to the many studies that assess the effect of mycorrhizae on plant uptake of P, only few of them report how mycorrhizae affect P leaching. This is usually not regarded as a major pathway of P export from a field because of the high affinity of phosphate  to soil Mycorrhizae are involved in most aspects of P cycling as can be seen in It has long been recognized that a functioning riparian forest can retain nutrients exported from agriculture . They haPhalaris aquatica L investigated the effects of AMF on plant growth, nutrient depletion from soil and leaching via water. The results indicate that where P was added, P levels in both the soil and water were significantly lower in the mycorrhizal inoculated plants compared to the non-inoculated plants. These results suggest riparian management practices which promote mycorrhizae could help minimize nutrient loss. What is most significant about this study is that it occurs in Australia’s nutrient-challenged riparian ecosystems, demonstrating how increasing this below-ground diversity can support nutrient interception in areas which experience rapid influxes of nutrients [However, riparian watersheds have been under strong development pressure. Conversion of these forests to cropland or grazing  has led utrients . In theoutrients , thus byPopulus deltoides in this case) was higher than herbaceous vegetative uptake [−1 over four years; 63% higher than in a control stand of smooth brome (Bromis inermis). Willows are suggested frequently for phytoremediation projects [Plant uptake in buffers and bioretention projects can be significant, depending on plant species, type, and age . For exae uptake  and the projects  because projects , which mStorage of P in buffer strips is not forever and release of P occurs at different time scales. Release may be associated with seasonal cycles such as growing and senescence periods of vegetation and the associated decomposition of dead plant material, and release of phosphate from labile mineral pools during flooding events. Ultimately removal of P has to be managed by harvesting perennial vegetation ,155, so Harvesting buffer zone grasses and woody biomass removes accumulated P and prevents P saturation, increasing P retention and decreasing SRP losses in surface runoff . In partIn urban and suburban landscapes, green infrastructure systems require a phytoextraction element to combat the inevitable P saturation which occurs over time in buffers, constructed wetlands (CW), and bioretention systems . GeneralGreen roofs provide a range of ecosystem services such as stormwater retention, temperature moderation, urban biodiversity, carbon sequestration, and enhanced aesthetics . It is iCarex stipata reduced TP by 13–48% and SRP by 14–60% [Bioretention is a common BMP which involves stormwater flowing through a vegetated area with engineered soil mixes . Bioretey 14–60% .Like some riparian areas, constructed wetlands (CWs) are characterized by wet to inundated soils. Since the 1950s, CWs have been studied as low technology methods to treat wastewater from agriculture , residenAvena barbata and Stipa pulchra, were used in this experiment. For Avena barbata, the shoot and root concentrations were diminished by the presence of mycorrhizae in the greenhouse, but not in the field experiment. Yet, the data showed consistently that for Stipa pulchra, P concentrations were greater in the mycorrhizal treatment regardless of the experimental setting. It is not clear whether these inconsistent results are artifacts of using a fungicide. However, the negative effects of mycorrhizae on plant P have also been reported by others for certain experimental conditions. These include large additions of P in sewage sludge [Trifolium subterraneum took in less P with mycorrhizae present when P was added [Medicago trunculata. At longer incubation periods, the effect of both root and shoot P were less after 49 than 35 days. The effect of mycorrhizal presence was negative for shoots after 49 days [Zea mays) [e sludge  when addas added . This is 49 days . In anotea mays)  throughoThe effect of increased plant P uptake should translate into reduced soil P if no additional fertilizer is added. Because of the large amount of P stored, adsorbed to soil colloids, it is difficult to detect a decrease in the total P fraction in the soil. However, extractable P has been shown to be reduced when corn is inoculated with mycorrhizae and is grown with no P fertilizer. This is consistent with increased P uptake by the plants. Extractable soil P is not significantly different between mycorrhizal and non-mycorrhizal treatments when P fertilizer is added .Lolium multiflora and mycorrhizae Rhizoglomus irregular, leaching increased by 45%, but for its combination with mycorrhizae Funnelformis mosseae, P leaching decreased by 19.5% [Trifolium pratense was combined with three mycorrhizae, no significant differences were observed [Consequently, losses of P from the soil as leaching or runoff would also be expected to be reduced when mycorrhizae are present. This has indeed been shown in several laboratory column studies ,121,129.observed .Little research has been conducted on the deliberate incorporation of mycorrhizae into phytoremediation strategies for mitigating P loading to freshwater. In particular, research is needed into their role in restoring riparian buffers and subsequently in the interception of P by the mycorrhizae–plant communities. An important question in this context is “how do mycorrhizae influence the trajectory of succession” after the initial restoration plantings. Closely linked to this question is how much P can the plant community extract and whether removal of plant material is feasible while facilitating ecosystem recovery. Comparing restorations with high and low biodiversity may yield information on the efficacy of P mitigation in buffers with these additional practices. Succession may also be affected by the P status of the riparian area and thus the fate of any P accumulating plants  and theiAnother promising area in need of research involves the potential of source reduction to decrease fertilizer needs. Specific crop combinations, cover crops, and green manures can be used to reduce fertilizer needs. Some grain crops have the ability to mobilize P from unavailable pools and thus transfer P to subsequent crops as their residues decompose ,175,176.Unlike crop rotations, intercropping of P mobilizing and non-mobilizing plants ,178 thatImpatiens glandulifera, which has invaded both European and North American riparian areas interferes with mycorrhizae [Reynoutria japonica, a non-mycorrhizal plant suppresses mycorrhizae and reduces their diversity [Although there seem to be some combinations of plants that can leverage the mycorrhizal associations for better P removal, there are examples of plants that suppress the establishment of the symbiosis. Studies have mainly focused on invasive plants that reduce AMF infections. For example, Himalayan impatience, orrhizae . Similariversity . Howeveriversity . A generiversity .Phragmites australis effectively uptake excess nutrients such as P. As a phytoaccumulator in areas of intensive vegetation [Typha latifolia [While there is debate about whether non-native species are ecosystem place holders during climate change or actually malaffect native habitats and threaten ecosystem resilience ,184 certgetation  these spatifolia  are wortOne confounding factor in myco-phytoremediation that makes it difficult to compare results is that currently researchers use either commercial inoculant or inoculant extracted from the wild. There are distinctions in the effectiveness between and within these two sources of inoculant which is not yet clearly determined. Standardized studies that compare how commercial vs. locally gathered and propagated mycorrhizae affect P cycling may help interpret the results of these two experimental approaches.As 400 million-year-old symbiotic weavers of ecosystems with now 80% of terrestrial plants, mycorrhizae hold the keys to reducing P pollution from upland accumulations. Researching specific plant–mycorrhizae associations for P removal from soils and applying these findings to critical source areas on farms, urban conduits, and suburban corridors can benefit water quality.The mycorrhizal effects that have been quantified, such as plant uptake and reductions in soil and leachate concentrations, show promise for reducing phosphorus pollution by myco-phytoremediation. A holistic approach that combines source reduction, interception, and prevention should be considered across the landscape scale. This involves nutrient management based on precision farming, plant breeding, crop rotation, intercropping, microbial engineering, microbial–fungal–floral symbiosis, increased perennial green infrastructures, and deliberate harvesting. This integrated approach, known as ‘agro-engineering’ , facilitMycorrhizal research in the context of water quality is scarce. Methods need to be developed and tested to help agriculture become more regenerative and urban stormwater infrastructure more effective. Tools are also needed which accurately assess current mycorrhizal presence in ecosystems to which land managers can respond accordingly. As we develop more understanding of what AMF and ECM taxa are present and how they react to different soil treatments, microbes and flora , a more