No abstract

Boronic acids are well-known for their ability to complex with saccharides and to form cyclic boronic esters or cyclic boronate ions. Increasing the reactivity of boronic acids would lead towards the design of a highly responsive sensor for non-enzymatic glucose monitoring applications. Many studies have been carried out to investigate the reactivity of boronic acids towards diols in different environmental effects. The symmetry around boron in their reactive species, however, is still an open question. In this study, we used computational quantum chemistry calculations to propose a model in which boronic acid is highly reactive towards diols. B3LYP/6-31+G(d,p) model chemistry was used in water to calculate the transition states of several proposed reaction mechanisms and the rates of the reactions were calculated using the transition state theory. The reaction takes place in two steps with the first step known as the rate determining step. The model we proposed in this study includes two different electronegative R-groups attached to boronic acid (i.e. CF 3 and CH 3) which highly influence the interaction of boron with diols. The kinetic results in our study show that boronate ion with a low electronegative R-group is a better sensor in alkaline medium and boronic acid with a high electronegative R-group is a better sensor in acidic medium. Using the latter in alkaline medium results in a very poor sensor since it is highly reactive and promptly forms a tetrahedral boronate ion. The high electronegative R-group on boronate ion decreases its basic characteristics and results in a low reactive sensor. The same scenario goes for the former i.e. boronate ion attached to a low electronegative R-group in acidic medium. As a result, we can conclude that boronic acid's reactivity is not mainly due to the symmetry around boron, it is due to the characteristics of boron itself which can be affected by both the R-group and the medium.

No abstract

The P-site-A76-2′OH transfers the polypeptide chain to the A-site α-amine and A2451 facilitates this transfer by acting as proton shuttle.

In this study, the interaction of seven potential inhibitors in complex with SARS-CoV-2’s M protease (Mpro) is modelled and optimized using ONIOM (Own N-layered Integrated molecular Orbital and molecular Mechanics; QM/MM) approach. Density functional theory is used for the small system and Universal Force Field is used for the rest of the molecule with ONIOM (m062x/6-311++G (d,p):UFF) model chemistry. The seven inhibitors that are used in this study are N3, ebselen, disulfiram, tideglusib, carmofur, shikonin and PX-12. The calculated interaction energy between the inhibitor and Mpro shows a strong inhibition of Mpro activity with N3, ebselen as well as PX-12 inhibitors. The two former inhibitors are previously reported as strong inhibitors; however, the strong inhibition effect of PX-12 has not been previously reported. The results of this study can provide useful insight into designing an effective inhibitor drug for SARS-nCoV, suggesting a better inhibition from PX-12 than ebselen.