The 1,3-dipolar cycloaddition of cyclooctynes with azides, also called "copper-free click chemistry", is a bioorthogonal reaction with widespread applications in biological discovery. The kinetics of this reaction are of paramount importance for studies of dynamic processes, particularly in living subjects. Here we performed a systematic analysis of the effects of strain and electronics on the reactivity of cyclooctynes with azides through both experimental measurements and computational studies using a density functional theory (DFT) distortion/interaction transition state model. In particular, we focused on biarylazacyclooctynone (BARAC) because it reacts with azides faster than any other reported cyclooctyne and its modular synthesis facilitated rapid access to analogues. We found that substituents on BARAC's aryl rings can alter the calculated transition state interaction energy of the cycloaddition through electronic effects or the calculated distortion energy through steric effects. Experimental data confirmed that electronic perturbation of BARAC's aryl rings has a modest effect on reaction rate, whereas steric hindrance in the transition state can significantly retard the reaction. Drawing on these results, we analyzed the relationship between alkyne bond angles, which we determined using X-ray crystallography, and reactivity, quantified by experimental second-order rate constants, for a range of cyclooctynes. Our results suggest a correlation between decreased alkyne bond angle and increased cyclooctyne reactivity. Finally, we obtained structural and computational data that revealed the relationship between the conformation of BARAC's central lactam and compound reactivity. Collectively, these results indicate that the distortion/interaction model combined with bond angle analysis will enable predictions of cyclooctyne reactivity and the rational design of new reagents for copper-free click chemistry.
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http://dx.doi.org/10.1021/ja3000936 | DOI Listing |
ACS Appl Mater Interfaces
December 2024
Institute of Chemistry, Federal University of Mato Grosso do Sul, Avenida Senador Filinto Muller 1555, Campo Grande, Mato Grosso do Sul 79074-460, Brazil.
There has been huge interest among chemical scientists in the electrochemical reduction of nitrate (NO) to ammonia (NH) due to the useful application of NH in nitrogen fertilizers and fuel. To conduct such a complex reduction reaction, which involves eight electrons and eight protons, one needs to develop high-performance (and stable) electrocatalysts that favor the formation of reaction intermediates that are selective toward ammonia production. In the present study, we developed and applied CoO/graphene nanoribbon (GNR) electrocatalysts with excellent properties for the effective reduction of NO to NH, where NH yield rate of 42.
View Article and Find Full Text PDFACS Appl Mater Interfaces
December 2024
Department of Materials Science and Engineering, Chosun University, Gwangju 61452, Korea.
With the applications of in situ X-ray diffraction (XRD), electrical - measurement, and ambient pressure hard X-ray photoelectron spectroscopy (AP-HAXPES), the characteristics of the topotactic phase transition of LaCoO (LCO) thin films are examined. XRD measurements show clear evidence of structural phase transition (SPT) of the LCO thin films from the perovskite (PV) LaCoO to the brownmillerite (BM) LaCoO phases through the intermediate LaCoO phase at a temperature of 350 °C under high-vacuum conditions, ∼10 mbar. The reverse SPT from BM to PV phases is also found under ambient pressure (>100 mbar) of air near 100 °C.
View Article and Find Full Text PDFInorg Chem
December 2024
Departamento de Química Inorgánica, Facultad de Química, Universidad de Murcia, Campus de Espinardo 19, Murcia 30100, Spain.
Unsymmetrical bis-cyclometalated dicarboxylato complexes (-6-32)-[Pt(tpy)(OCR)] [tpy = cyclometalated 2-(-tolyl)pyridine, R = -Bu (), Me (), Ph (), CF ()], are obtained from the reaction of -[Pt(tpy)] with the appropriate PhI(OCR) reagent. Treatment of complexes of this type with different carboxylates (R'CO) results in the formation of mixed-carboxylato derivatives, namely (-6-43)-[Pt(tpy)(OCMe)(OCR')] [R' = -Bu (), CF (), Ph ()], (-6-34)-[Pt(tpy)(OCCF)(OCR')] [R' = -Bu (), Me (), Ph ()], and (-6-34)-[Pt(tpy)(OC--Bu)(OCMe)] (). Irradiation of - and - with UV light (365 nm) in MeCN gives 5-methyl-2-(2-pyridyl)phenyl pivalate (), 5-methyl-2-(2-pyridyl)phenyl acetate () or 5-methyl-2-(2-pyridyl)phenyl benzoate () as the major photoproduct from most complexes, resulting from a reductive C-O coupling between a tpy ligand and a carboxylato ligand.
View Article and Find Full Text PDFJ Chem Theory Comput
December 2024
School of Pharmaceutical Sciences and Institute of Pharmaceutical Sciences of Western Switzerland (ISPSO), University of Geneva, Rue Michel Servet 1, 1206 Genève, Switzerland.
We introduce an enhanced sampling algorithm to obtain converged free energy landscapes of molecular rare events, even when the collective variable (CV) used for biasing is not optimal. Our approach samples a time-dependent target distribution by combining the on-the-fly probability enhanced sampling and its exploratory variant, OPES Explore. This promotes more transitions between the relevant metastable states and accelerates the convergence speed of the free energy estimate.
View Article and Find Full Text PDFTrop Med Infect Dis
December 2024
Hubert Department of Global Health, Rollins School of Public Health, Emory University, 1518 Clifton Road, Atlanta, GA 30322, USA.
Although every youth in pediatric/adolescent HIV care will need to transition to adult-oriented care, there are no existing evidence-based interventions to optimize health through this process. Healthcare transition poses a persistent challenge to the health of youth living with HIV, which may result in gaps in care engagement, medication adherence, and viral suppression. Our process evaluation of , a multilevel mobile health (mHealth) intervention, included iterative interviews with youth, providers, and Transition Champions.
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