Antimicrobial Activity of Rhenium Di- and Tricarbonyl Diimine Complexes: Insights on Membrane-Bound S. aureus Protein Binding

Antimicrobial resistance is one of the major human health threats, with significant impacts on the global economy. Antibiotics are becoming increasingly ineffective as drug-resistance spreads, imposing an urgent need for new and innovative antimicrobial agents. Metal complexes are an untapped source of antimicrobial potential. Rhenium complexes, amongst others, are particularly attractive due to their low in vivo toxicity and high antimicrobial activity, but little is known about their targets and mechanism of action. In this study, a series of rhenium di- and tricarbonyl diimine complexes were prepared and evaluated for their antimicrobial potential against eight different microorganisms comprising Gram-negative and -positive bacteria. Our data showed that none of the Re dicarbonyl or neutral tricarbonyl species have either bactericidal or bacteriostatic potential. In order to identify possible targets of the molecules, and thus possibly understand the observed differences in the antimicrobial efficacy of the molecules, we computationally evaluated the binding affinity of active and inactive complexes against structurally characterized membrane-bound S. aureus proteins. The computational analysis indicates two possible major targets for this class of compounds, namely lipoteichoic acids flippase (LtaA) and lipoprotein signal peptidase II (LspA). Our results, consistent with the published in vitro studies, will be useful for the future design of rhenium tricarbonyl diimine-based antibiotics

(E)-1-(4-Meth­oxy­anthracen-1-yl)-2-phenyl­diazene

The title compound, C21H16N2O, has an E-conformation about the diazene N=N bond. It is reasonably planar with the phenyl ring being inclined to the mean plane of the anthracene moiety [planar to within 0.077 (3) Å] by 6.43 (10)°. The crystal structure is stabilized by C—H⋯π and weak π–π inter­actions [centroid–centroid distances of 3.7192 (16) and 3.8382 (15) Å], leading to the formation of two-dimensional networks stacking along [001] and lying parallel to (110)

Efficient Direct Nitrosylation of alpha-Diimine Rhenium Tricarbonyl Complexes to Structurally Nearly Identical Higher Charge Congeners Activable towards Photo-CO Release

The reaction of rhenium alpha-diimine (N-N) tricarbonyl complexes with nitrosonium tetrafluoroborate yields the corresponding dicarbonyl-nitrosyl [Re(CO)(2)(NO)(N-N)X](+) species (where X = halide). The complexes, accessible in a single step in good yield, are structurally nearly identical higher charge congeners of the tricarbonyl molecules. Substitution chemistry aimed at the realization of equivalent dicationic species (intended for applications as potential antimicrobial agents), revealed that the reactivity of metal ion in [Re(CO)(2)(NO)(N-N)X](+) is that of a hard Re acid, probably due to the stronger pi-acceptor properties of NO+ as compared to those of CO. The metal ion thus shows great affinity for pi-basic ligands, which are consequently difficult to replace by, e.g., sigma-donor or weak pi-acids like pyridine. Attempts of direct nitrosylation of alpha-diimine fac-[Re(CO)(3)](+) complexes bearing pi-basic OR-type ligands gave the [Re(CO)(2)(NO)(N-N)(BF4)][BF4] salt as the only product in good yield, featuring a stable Re-FBF3 bond. The solid state crystal structure of nearly all molecules presented could be elucidated. A fundamental consequence of the chemistry of [Re(CO)(2)(NO)(N-N)X](+) complexes, it that the same can be photo-activated towards CO release and represent an entirely new class of photoCORMs

A concept for stimulated proton transfer in 1-(phenyldiazenyl)naphthalen-2-ols

A series of aryl azo derivatives of naphthols (1–3) were studied by means of UV–Vis and NMR spectroscopy in different solvents as well as by quantum chemical calculations and X-ray analysis. Previous studies have shown that Sudan I (1) exists as a tautomeric mixture. The effect of the solvents is minimized by the existing intramolecular hydrogen bond. Therefore, the influence on the tautomeric state in structurally modified 1 has been investigated. Structure 2 contains an additional OH- group, which deprotonates easily and affects the position of the tautomeric equilibrium by changing the electronic properties of the substituent. The implementation of a sidearm in 3 creates a condition for competition between the nitrogen from the azo group and from the piperidine unit for the tautomeric proton. In this case the use of acid as a stimulus for controlling the tautomeric process was achieved

Supplementary material for the article: Savić, N. D.; Vojnovic, S.; Glišić, B. Đ.; Crochet, A.; Pavic, A.; Janjić, G. V.; Pekmezović, M.; Opsenica, I. M.; Fromm, K. M.; Nikodinovic-Runic, J.; et al. Mononuclear Silver(I) Complexes with 1,7-Phenanthroline as Potent Inhibitors of Candida Growth. Eur. J. Med. Chem. 2018, 156, 760–773. https://doi.org/10.1016/j.ejmech.2018.07.049

Supplementary data for: [https://doi.org/10.1016/j.ejmech.2018.07.049]Research data for this article: [https://www.ccdc.cam.ac.uk/structures/search?id=doi:10.5517/ccdc.csd.cc1zdr7c&sid=DataCite]Research data for this article: [https://www.ccdc.cam.ac.uk/structures/search?id=doi:10.5517/ccdc.csd.cc1zdr6b&sid=DataCite]Research data for this article: [https://www.ccdc.cam.ac.uk/structures/search?id=doi:10.5517/ccdc.csd.cc1zdr59&sid=DataCite]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2213]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/2993

Synthesis, characterization, and in vivo evaluation of the anticancer activity of a series of 5- and 6-(halomethyl)-2,2′-bipyridine rhenium tricarbonyl complexes

We report the synthesis, characterization, and in vivo evaluation of the anticancer activity of a series of 5- and 6-(halomethyl)-2,2′-bipyridine rhenium tricarbonyl complexes. The study was promoted in order to understand if the presence and position of a reactive halomethyl substituent on the diimine ligand system of fac-[Re(CO)3]+ species may be a key molecular feature for the design of active and non-toxic anticancer agents. Only compounds potentially able to undergo ligand-based alkylating reactions show significant antiproliferative activity against colorectal and pancreatic cell lines. Of the new species presented in this study, one compound (5-(chloromethyl)-2,2′-bipyridine derivative) shows significant inhibition of pancreatic tumour growth in vivo in zebrafish-Panc-1 xenografts. The complex is noticeably effective at 8 μM concentration, lower than its in vitro IC50 values, being also capable of inhibiting in vivo cancer cells dissemination

Supplementary material for the article: Savić, N. D.; Vojnovic, S.; Glišić, B. Đ.; Crochet, A.; Pavic, A.; Janjić, G. V.; Pekmezović, M.; Opsenica, I. M.; Fromm, K. M.; Nikodinovic-Runic, J.; et al. Mononuclear Silver(I) Complexes with 1,7-Phenanthroline as Potent Inhibitors of Candida Growth. Eur. J. Med. Chem. 2018, 156, 760–773. https://doi.org/10.1016/j.ejmech.2018.07.049

Supplementary data for: [https://doi.org/10.1016/j.ejmech.2018.07.049]Research data for this article: [https://www.ccdc.cam.ac.uk/structures/search?id=doi:10.5517/ccdc.csd.cc1zdr7c&sid=DataCite]Research data for this article: [https://www.ccdc.cam.ac.uk/structures/search?id=doi:10.5517/ccdc.csd.cc1zdr6b&sid=DataCite]Research data for this article: [https://www.ccdc.cam.ac.uk/structures/search?id=doi:10.5517/ccdc.csd.cc1zdr59&sid=DataCite]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2213]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/2993