Physicochemical and Theoretical Characterization of a New Small Non-Metal Schiff Base with a Differential Antimicrobial Effect against Gram-Positive Bacteria

Abstract

Searching for adequate and effective compounds displaying antimicrobial activities, especially against Gram-positive bacteria, is an important research area due to the high hospitalization and mortality rates of these bacterial infections in both the human and veterinary fields. In this work, we explored (E)-4-amino-3-((3,5-di-tert-butyl-2-hydroxybenzylidene)amino) benzoic acid (SB-1, harboring an intramolecular hydrogen bond) and (E)-2-((4-nitrobenzilidene)amino)aniline (SB-2), two Schiff bases derivatives. Results demonstrated that SB-1 showed an antibacterial activity determined by the minimal inhibitory concentration (MIC) against Staphylococcus aureus, Enterococcus faecalis, and Bacillus cereus (Gram-positive bacteria involved in human and animal diseases such as skin infections, pneumonia, diarrheal syndrome, and urinary tract infections, among others), which was similar to that shown by the classical antibiotic chloramphenicol. By contrast, this compound showed no effect against Gram-negative bacteria (Klebsiella pneumoniae, Escherichia coli, and Salmonella enterica). Furthermore, we provide a comprehensive physicochemical and theoretical characterization of SB-1 (as well as several analyses for SB-2), including elemental analysis, ESMS, 1H and 13C NMR (assigned by 1D and 2D techniques), DEPT, UV-Vis, FTIR, and cyclic voltammetry. We also performed a computational study through the DFT theory level, including geometry optimization, TD-DFT, NBO, and global and local reactivity analyses.

Why are the local hyper-softness and the local softness more appropriate local reactivity descriptors than the dual descriptor and the Fukui function, respectively?

“…This change of natural variables provides equivalent descriptors to Fukui functions and dual descriptors, namely the local softness [3] and local hypersoftness [13,14,15,16,17,18,19,20,21,22], respectively. They both have demonstrated to be useful for making comparisons of local reactivities among a variety of molecular systems.…”

“…Dual descriptor has the advantage of presenting nucleophilic and electrophilic regions on molecules in just one picture, however it is affected worse than Fukui function as the system's size increases because is an sub-intensive property of degree −2 which means that it is not possible to make comparisons of local reactivities among different molecular systems. To remedy this undesirable behavior it is a common practice to replace Fukui function f (r) with local softness s(r) and dual descriptor f (2) (r) with local hyper-softness s (2) (r) [13,14,15,16,17,18,19,20,21,22] respectively. It will be demonstrated the conceptual support for these replacements.…”

Intramolecular Hydrogen Bond in Pyridine Schiff Bases as Ancillary Ligands of Re(I) Complexes Is a Switcher between Visible and NIR Emissions: A Relativistic Quantum Chemistry Study

“…In addition, it was reported that, in studies involving only the PSB (i.e., [( E )-2­((3-amino-pyridin-4-ylimino)-methyl)-4,6-diterbutylphenol]), the H-bond stability is independent of the solvent polarity . This same result was also observed with other similar Schiff bases harboring an IHB. ,, Furthermore, confocal microscopy studies performed with these complexes, diluted stock in DMSO, allowed for obtaining successful images in the visible range. − , All these results argue for the IHB’s high stability, even in the presence of protic solvents or in cellular environments. Finally, if the IHB was unstable in biological conditions due to protic environments, we would observe that the complexes would exhibit different emissions dependent on the cellular compartment, for example, the cytoplasm (protic medium) or cell membranes (aprotic medium), potentially generating a differential staining.…”

“…To study the IHB in more detail, we evaluated the second-order interaction energy through NBO calculations. − The interaction energy is related to stabilizing donor–acceptor interactions due to electron delocalization concerning the zeroth-order natural Lewis structure. , In addition, NBO analysis provides an efficient method for studying the participation of the IHB in the stability of N-harboring compounds …”

“…69 This same result was also observed with other similar Schiff bases harboring an IHB. 35,70,71 Furthermore, confocal microscopy studies performed with these complexes, diluted stock in DMSO, allowed for obtaining successful images in the visible range. [2][3][4]12 All these results argue for the IHB's high stability, even in the presence of protic solvents or in cellular environments.…”