Selected Electrosynthesis of 3-Aminopyrazoles from α,ß-Alkynic Hydrazones and Secondary Amines.

An available and simple electromediated cyclization method for 3-amino-substituted pyrazoles by using α,ß-alkynic hydrazone and secondary amine is described. The strategy utilizes KI as an electrolyte in an undivided cell with a constant current, generating the desired products in moderate-to-good yield. The method features selective amination at the 3-position of the pyrazole skeleton. The results indicate that α,ß-alkynic hydrazones functionalized with aromatic groups and secondary amines functionalized with electron-rich groups were better tolerated in this transformation.

Improved synthesis and evaluation of preclinical pharmacodynamic parameters of a new monocyclic ß-lactam DPI-2016.

Monocyclic ß-lactams are stable to a number of ß-lactamases and are the focus of researchers for the development of antibacterial drugs, particularly against Enterobacterales. We recently synthesized and reported the bactericidal activity of diverse series of aztreonam appended with amidine moieties as siderophores. One of the derivatives exhibiting the highest MIC value in vitro was selected for further preclinical studies. The compound DPI-2016 was reassessed for its synthetic routes and methods that were improved to find the maximum final yields aimed at large-scale synthesis. In addition, the results of the pharmacological studies were determined with reference to aztreonam. It has been found that the compound DPI-2016 showed comparable or slightly improved ADMET as well as pharmacokinetic parameters to aztreonam. It is estimated that the compound could be a potential lead for further clinical evaluation.

Recent Developments to Cope the Antibacterial Resistance via ß-Lactamase Inhibition.

Antibacterial resistance towards the ß-lactam (BL) drugs is now ubiquitous, and there is a major global health concern associated with the emergence of new ß-lactamases (BLAs) as the primary cause of resistance. In addition to the development of new antibacterial drugs, ß-lactamase inhibition is an alternative modality that can be implemented to tackle this resistance channel. This strategy has successfully revitalized the efficacy of a number of otherwise obsolete BLs since the discovery of the first ß-lactamase inhibitor (BLI), clavulanic acid. Over the years, ß-lactamase inhibition research has grown, leading to the introduction of new synthetic inhibitors, and a few are currently in clinical trials. Of note, the 1, 6-diazabicyclo [3,2,1]octan-7-one (DBO) scaffold gained the attention of researchers around the world, which finally culminated in the approval of two BLIs, avibactam and relebactam, which can successfully inhibit Ambler class A, C, and D ß-lactamases. Boronic acids have shown promise in coping with Ambler class B ß-lactamases in recent research, in addition to classes A, C, and D with the clinical use of vaborbactam. This review focuses on the further developments in the synthetic strategies using DBO as well as boronic acid derivatives. In addition, various other potential serine- and metallo- ß-lactamases inhibitors that have been developed in last few years are discussed briefly as well. Furthermore, binding interactions of the representative inhibitors have been discussed based on the crystal structure data of inhibitor-enzyme complex, published in the literature.

Effect of Extending the Conjugation of Dye Molecules on the Efficiency and Stability of Dye-Sensitized Solar Cells.

We designed and synthesized two organic dyes (A6 and A10) for dye-sensitized solar cells (DSSCs) by extending the molecular conjugation strategy. The sensitizer A10 was constructed by inserting ethene into our previously reported sensitizer AZ6. The sensitizer A6 was obtained by further substituting the hydrogen of ethene with another donor (D) and π-bridge-acceptor (π-A) segment. The UV-vis spectra and J-V curves showed that the dyes A10 and A6 could effectively facilitate the light-harvesting and photocurrent densities with respect to AZ6. Consequently, the A10-based DSSC achieved an enhanced efficiency (8.54%) with a high photocurrent (18.81 mA cm-2). Desorption experiments of dyes adsorbed on TiO2 showed that compared with the monoanchoring dyes AZ6 and A10, the dianchoring configuration effectively strengthened the affinity of dye A6 with the photoanode, making it more difficult to leach from the photoanode. The A6-based DSSC shows outstanding stability, and its overall efficiency could remain 98.0% of its initial value after 3000 h of aging time, exceeding that of its monoanalogue AZ6 (remained 78.3% after 3000 h).

Effect of the Spatial Configuration of Donors on the Photovoltaic Performance of Double D-π-A Organic Dyes.

Three double D-π-A sensitizers (A1, A3, and A5) containing different donors (triphenylamine, methoxy-modified triphenylamine, and cyclic thiourea-functionalized triphenylamine) are synthesized to investigate the role of different donors in dye-sensitized solar cells (DSSCs). Detailed investigations of the sensitizers reveal that the spatial characteristics of donor units have a considerable impact on the light-harvesting, electrochemistry, and photovoltaic properties. Benefiting from the strong shielding ability of alkyl chains in the donor to its branch chains as observed in density functional theory (DFT), the open-circuit voltage (VOC = 712.0 mV) of A5-based DSSC is higher than those of A1 and A3 by 90 and 78 mV, respectively. Therefore, the A5-based DSSC delivers a good efficiency of 8.54%, relying on its effective suppression of interfacial recombination. The results indicate that the judiciously tailored donor unit is an effective approach to optimize dye configurations to further improve power conversion efficiencies.