Understanding the nature of charge transfer mechanisms in 3-dimensional metal-organic frameworks (MOFs) is an important goal owing to the possibility of harnessing this knowledge to design electroactive and conductive frameworks. These materials have been proposed as the basis for the next generation of technological devices for applications in energy storage and conversion, including electrochromic devices, electrocatalysts, and battery materials. After nearly two decades of intense research into MOFs, the mechanisms of charge transfer remain relatively poorly understood, and new strategies to achieve charge mobility remain elusive and challenging to experimentally explore, validate, and model. We now demonstrate that aromatic stacking interactions in Zn(II) frameworks containing cofacial thiazolo[5,4- d]thiazole (TzTz) units lead to a mixed-valence state upon electrochemical or chemical reduction. This through-space intervalence charge transfer (IVCT) phenomenon represents a new mechanism for charge transfer in MOFs. Computational modeling of the optical data combined with application of Marcus-Hush theory to the IVCT bands for the mixed-valence framework has enabled quantification of the degree of charge transfer using both in situ and ex situ electro- and spectro-electrochemical methods. A distance dependence for the through-space electron transfer has also been identified on the basis of experimental studies and computational calculations. This work provides a new window into electron transfer phenomena in 3-dimensional coordination space, of relevance to electroactive MOFs where new mechanisms for charge transfer are highly sought after, and to understanding biological light-harvesting systems where through-space mixed-valence interactions are operative.

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Incorporation of D-amino acids into peptidoglycan is a unique metabolic feature of bacteria. Since D-amino acids are not metabolic substrates in most mammalian tissues, this difference can be exploited to detect living bacteria in vivo. Given the prevalence of D-alanine in peptidoglycan muropeptides, as well as its role in several antibiotic mechanisms, we targeted this amino acid for positron emission tomography (PET) radiotracer development. D-[3-11 C]Alanine and the dipeptide D-[3-11 C]alanyl-Dalanine were synthesized via asymmetric alkylation of glycine-derived Schiff-base precursors with [ 11 C]methyl iodide in the presence of a cinchonidinium phase-transfer catalyst. In cell experiments, both tracers showed accumulation by a wide variety of both Grampositive and Gram-negative pathogens including Staphylococcus aureus and Pseudomonas aeruginosa. In a mouse model of acute bacterial myositis, D-[3-11 C]alanine was accumulated by living microorganisms but was not taken up in areas of sterile inflammation.When compared to existing clinical nuclear imaging tools, specifically 2-deoxy-2-[ 18 F]fluoro-D-glucose and a gallium citrate radiotracer, D-alanine showed more bacteria-specific uptake. Decreased D-[3-11 C]alanine uptake was also observed in antibioticsensitive microbes after antimicrobial therapy, when compared to that in resistant organisms. Finally, prominent uptake of D-[3-11 C]alanine uptake was seen in rodent models of discitis-osteomyelitis and P. aeruginosa pneumonia. These data provide strong justification for clinical translation of D-[3-11 C]alanine to address a number of important human infections.

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The reaction of oxidized bovine cytochrome c oxidase (bCcO) with hydrogen peroxide (H2O2) was studied by electron paramagnetic resonance (EPR) to determine the properties of radical intermediates. Two distinct radicals with widths of 12 and 46 G are directly observed by X-band EPR in the reaction of bCcO with H2O2 at pH 6 and pH 8. High-frequency EPR (D-band) provides assignments to tyrosine for both radicals based on well-resolved g-tensors. The wide radical (46 G) exhibits g-values similar to a radical generated on L-Tyr by UV-irradiation and to tyrosyl radicals identified in many other enzyme systems. In contrast, the g-values of the narrow radical (12 G) deviate from L-Tyr in a trend akin to the radicals on tyrosines with substitutions at the ortho position. X-band EPR demonstrates that the two tyrosyl radicals differ in the orientation of their β-methylene protons. The 12 G wide radical has minimal hyperfine structure and can be fit using parameters unique to the post-translationally modified Y244 in bCcO. The 46 G wide radical has extensive hyperfine structure and can be fit with parameters consistent with Y129. The results are supported by mixed quantum mechanics and molecular mechanics calculations. In addition to providing spectroscopic evidence of a radical formed on the post-translationally modified tyrosine in CcO, this study resolves the much debated controversy of whether the wide radical seen at low pH in the bovine enzyme is a tyrosine or tryptophan. The possible role of radical formation and migration in proton translocation is discussed.

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BackgroundPeople who inject drugs (PWID) are at highest risk for hepatitis C virus (HCV) infection, yet many remain unaware of their infection status. New anti-HCV rapid testing has high potential to impact this.MethodsYoung adult (<30 years) active PWID were offered either the rapid OraQuick® or standard anti-HCV test involving phlebotomy, then asked to complete a short questionnaire about testing perceptions and preferences. Sample characteristics, service utilization, and injection risk exposures are assessed with the HCV testing choice as the outcome, testing preferences, and reasons for preference.ResultsOf 129 participants: 82.9% (n = 107) chose the rapid test. There were no significant differences between those who chose rapid vs. standard testing. A majority (60.2%) chose the rapid test for quick results; most (60.9%) felt the rapid test was accurate, and less painful (53.3%) than the tests involving venipuncture.ConclusionsOraQuick® anti-HCV rapid test was widely accepted among young PWID. Our results substantiate the valuable potential of anti-HCV rapid testing for HCV screening in this high risk population.

The formation of radicals in bovine cytochrome c oxidase (bCcO), during the O2 redox chemistry and proton translocation, is an unresolved controversial issue. To determine if radicals are formed in the catalytic reaction of bCcO under single turnover conditions, the reaction of O2 with the enzyme, reduced by either ascorbate or dithionite, was initiated in a custom-built rapid freeze quenching (RFQ) device and the products were trapped at 77 K at reaction times ranging from 50 µs to 6 ms. Additional samples were hand mixed to attain multiple turnover conditions and quenched with a reaction time of minutes. X-band (9 GHz) continuous wave electron paramagnetic resonance (CW-EPR) spectra of the reaction products revealed the formation of a narrow radical with both reductants. D-band (130 GHz) pulsed EPR spectra allowed for the determination of the g-tensor principal values and revealed that when ascorbate was used as the reductant the dominant radical species was localized on the ascorbyl moiety, and when dithionite was used as the reductant the radical was the SO2•− ion. When the contributions from the reductants are subtracted from the spectra, no evidence for a protein-based radical could be found in the reaction of O2 with reduced bCcO. As a surrogate for radicals formed on reaction intermediates, the reaction of hydrogen peroxide (H2O2) with oxidized bCcO was studied at pH 6 and pH 8 by trapping the products at 50 µs with the RFQ device to determine the initial reaction events. For comparison, radicals formed after several minutes of incubation were also examined, and X-band and D-band analysis led to the identification of radicals on Tyr-244 and Tyr-129. In the RFQ measurements, a peroxyl (R – O – O•) species was formed, presumably by the reaction between O2 and an amino acid-based radical. It is postulated that Tyr-129 may play a central role as a proton loading site during proton translocation by ejecting a proton upon formation of the radical species and then becoming reprotonated during its reduction via a chain of three water molecules originating from the region of the propionate groups of heme a3.