Electron Spin Resonance of Adenosine Triphosphate
IT has been suggested that in adenosine triphosphate (ATP) the phosphate chain and the adenine are linked by the pentose, so that the two terminal phosphates touch the two nitrogen atoms at positions 6 and 7 in the adenine ring1; and that, since triphosphate compounds might be electron acceptors and adenine is a good electron donor, the adenine group might donate an electron to the triphosphate group2. I. Isenberg and A. Szent-Györgyi2 obtained an electron spin resonance signal from ATP (di-sodium salt) which they attributed to internal charge transfer between the adenine and the triphosphate. They also suggested that there was a possibility that the signal could be due to a transition metal impurity in the form of a transition metal – ATP complex. In view of the great importance of ATP in living processes, we have re-examined the electron spin resonance of this compound to decide between these possibilities.
Electron spin resonance and its applications
The method of electron spin resonance spectroscopy for studying free radicals and related materials is outlined and the basic parts of the theory are given. Some typical spectrometers are indicated and details are given of the arrangement of samples of different kinds. Three systems are discussed in some detail, as examples, namely the spectrum of a free radical in irradiated alanine, the semiquinone spectrum in solution and the haemoglobin crystal structure problem. Reference is made to applications in biology and related fields; subjects of special importance include radiobiology, photosynthesis, enzymic oxidation and nucleic acid complexes.
Pharmacokinetics of Mivacurium Isomers and Their Metabolites in Healthy Volunteers after Intravenous Bolus Administration
Background Previous studies report the pharmacokinetics of mivacurium isomers after an infusion using venous blood sampling. Although the extent of the mivacurium arterial‐venous gradient is not known, the sampling site is likely to influence mivacurium pharmacokinetic parameters because the drug is rapidly metabolized as it traverses the circulation. The objectives of this study were (1) to determine the pharmacokinetics of mivacurium isomers in healthy persons after intravenous bolus administration using intensive arterial blood sampling, and (2) to characterize the formation and elimination of mivacurium metabolites in human plasma. Methods Eight persons classified as American Society of Anesthesiologists physical status 1 or 2 who were scheduled to undergo elective surgery under balanced anesthesia received 0.15 mg/kg mivacurium chloride as an intravenous bolus. Arterial blood samples were collected every 10 s during the first 2 min and at frequent intervals for 4 h thereafter. Plasma concentrations of mivacurium isomers and their metabolites were determined by two stereoselective high‐performance liquid chromatographic methods coupled with fluorometric detection and noncompartmental pharmacokinetic parameters. Results Mean elimination half‐lives of the trans‐trans, cis‐trans, and cis‐cis isomers were 2.4, 2, and 28.5 min, respectively, with corresponding mean plasma clearances of 29.2, 45.7, and 6.7 ml [center dot] min‐1 [center dot] kg‐1. The volumes of distribution at steady state of the trans‐trans, cis‐trans, and cis‐cis isomers were 0.047, 0.054, and 0.189 l/kg, respectively. Plasma concentrations of monoester and alcohol metabolites peaked 25 s (median) after mivacurium injection, with half‐lives in the range of 90 min, except for the cis alcohol metabolite, which was only negligibly and transiently formed. Conclusions Substantial hydrolysis of mivacurium isomers by cholinesterases was confirmed by the rapid appearance of mivacurium metabolites in plasma. The intensive arterial sampling proved to be critical for the trans‐trans and cis‐trans isomers because the area under the curve between 0 and 2 min accounted for 75% and 86% of the total, respectively.