Tsonko M. Kolev

The use of styrylium dyes as organic nonlinear optical materials in many photonics domains has been the subject of research for decades. It has been noted that over time, research has also looked into the biological activity of styrylium dyes, namely their antibacterial effects, as well as attempts to establish links between structure and property by choosing particular structural pieces. These investigations’ scope is still very limited. Therefore, our main goal was to synthesize a styrylium compound with antimicrobial potential. A novel styrylquinolinium compound (D) was synthesized using Knoevenagel condensation. Spectroscopic techniques, including IR, 1D and 2D NMR (COSY, HSQC, and HMBC), HRMS spectra, and X-ray analysis, were used to confirm its structure. The antimicrobial and anti-inflammatory activity of the compound was assessed. The compound was found to have very good antimicrobial activity against five Gram-positive strains, three Gram-negative strains, and fungi. The most pronounced effect of the compound was against Escherichia coli and Pseudomonas aeruginosa. The compound’s anti-inflammatory activity was evaluated through its ex vivo immunohistochemistry. DFT calculations, such as geometry optimization, Molecular Electrostatic Potential (MEP), HOMO–LUMO, reactivity parameters and molecular docking simulation were applied to investigate the electronic features of the compound and confirm the biological activity. The compound (D) demonstrated a promising antibacterial and immunomodulatory profile. Its ability to induce IL-1β and at the same time moderately reduce NOS3 can be considered as a controlled adaptation of the immune response, especially in cases requiring local immune activation. Docking simulation revealed that (D) binds effectively to the active site of the bacterial protein, supporting the experimental findings of the compound’s antibacterial activity.

A new styryl quinolinium dye (E)-4-(2-(2-hydroxynaphthalene-1-yl)ethenyl-1-octyl quinolinium iodide (3) was obtained by Knoevenagel condensation. Single crystal X-ray diffraction, spectral methods IR, 1H and 13C-NMR spectroscopy and TGA-DTA analysis were used to characterize the compound. The title compound crystallized in the triclinic space group P-1 and exhibited thermal stability up to 212 °C. The vibrational spectra were completely determined through the quantum chemical calculations.

Stilbenes, like resveratrol, are natural small molecules with several applications in the treatment of chronic illnesses, diabetes, and neurological and cardiovascular conditions. Considering the molecular structure of stilbenes and the biological activities of resveratrol, we investigated the synthesis and biological activity of a novel styryl quinolinium (SQ) derivative. The SQ was synthesized using the alkylation of lepidine and methyl 4-methylbenzenesulfonate and further Knoevenagel condensation with 2-hydroxy naphthaldehyde. Its structure was determined using NMR, IR, Raman, UV-Vis, and MS. The current trend of research has shifted toward the synthesis of novel SQ as resveratrol’s analog. Therefore, its anti-inflammatory and antioxidant activities were evaluated. The compound exerted very good anti-inflammatory effects in preventing albumin denaturation, which were confirmed by ex vivo immunohistochemical studies. Density functional theory (DFT) analyses were conducted on the SQ structure to gain detailed insights into its active sites, energy gap, quantum properties, and electronic behavior. The biological evaluation of the compound was completed, assessing its antioxidant potential using DPPH radical scavenging assay. In addition, molecular docking simulations were utilized to assess the SQ compound’s potential inhibitory effect on human serum albumin (HSA).

The title compound [systematic name: 1,10-phenanthrolinium 6-hydroxy-5-(oxidoimino)-1,3-diazinane-2,4-dione–6-hydroxy-5-(hydroxyimino)-1,3-diazinane-2,4-dione–water (1/1/5)], C₁₂H₉N₂ ⁺·C₄H₂N₃O₄ ⁻·C₄H₃N₃O₄·5H₂O, is a co-crystal salt hydrate comprising 1,10-phenanthrolinium cations, violurate anions, free violuric acid as co-former and five water molecules of crystallization per formula unit. The violurate and the violuric acid residues each form distinct N—H...O hydrogen-bonded tapes with a common R ² ₂(8) hydrogen-bond motif extending parallel to (103). Solvent water molecules connect the tapes to form a tri-periodic hydrogen-bonded network with channels extending parallel to the a-axis direction, which accommodate the N—H...O_water hydrogen-bonded 1,10-phenanthrolinium cations. Direct N—H...O hydrogen bonds between the 1,10-phenanthrolinium and violurate ions are not encountered.

Propane-1,3-diaminium squarate dihydrate, C₃H₁₂N₂ ²⁺·C₄O₄ ²⁻·2H₂O, results from the proton-transfer reaction of propane-1,3-diamine with squaric acid and subsequent crystallization from aqueous medium. The title compound crystallizes in the tetragonal crystal system (space group P4bm) with Z = 2. The squarate dianion belongs to the point group D _4h and contains a crystallographic fourfold axis. The propane-1,3-diaminium dication exhibits a C _2v -symmetric all-anti conformation and resides on a special position with mm2 site symmetry. The orientation of the propane-1,3-diaminium ions makes the crystal structure polar in the c-axis direction. The solid-state supramolecular structure features a triperiodic network of strong hydrogen bonds of the N—H...O and O—H...O types.

The crystal structure of 1,2,3,4-tetrahydroisoquinolin-2-ium (2S,3S)-3-carboxy-2,3-dihydroxypropanoate monohydrate, C₉H₁₂N⁺·C₄H₅O₆ ⁻·H₂O, at 115 K shows orthorhombic symmetry (space group P2₁2₁2₁). The hydrogen tartrate anions and solvent water molecules form an intricate diperiodic O—H...O hydrogen-bond network parallel to (001). The tetrahydroisoquinolinium cations are tethered to the anionic hydrogen-bonded layers through N—H...O hydrogen bonds. The crystal packing in the third direction is achieved through van der Waals contacts between the hydrocarbon tails of the tetrahydroisoquinolinium cations, resulting in hydrophobic and hydrophilic regions in the crystal structure.

Type II topoisomerases (TOP2s) play a key role in altering the DNA topology by transiently cleaving both strands of a DNA duplex. Therefore, increased TOP2 activity is associated with many cancers. Herein, we present the synthesis, structural characterization, virtual screening, and structural exploration, as well as evaluation of the antiproliferative effects of two new 4-substituted 2-(5,5-dimethyl-3-styrylcyclohex-2-enylidene)malononitrile derivatives with potential application in the drug design of isoform-specific TOP2 inhibitors. Both compounds 1 and 2 were verified by ESI-TOF-MS, NMR, and single-crystal X-ray diffraction (SCXRD) analysis. Furthermore, we applied our recently proposed SCXRD/HYdrogen DEsolvation (HYDE) technology platform in order to perform molecular modeling, virtual screening, and structural exploration with 1 and 2. For this purpose, we used the crystal structure of human TOP2β complexed to DNA and the anticancer drug etoposide. Moreover, we further evaluated the antiproliferative activity of 1 and 2 on human hepatocarcinoma HepG2 cells and compared the observed effects with those of the reference hTOP2β inhibitor etoposide. Based on the obtained results, compounds 1 and 2 showed a virtually higher binding affinity (K_{i HYDE} values) over etoposide towards hTOP2β but lower antiproliferative activity compared to those of etoposide.

Pyridin-4-ylmethanaminium perchlorate monohydrate (synonym: 4-picolylammonium perchlorate monohydrate), C₆H₉N₂ ⁺·ClO₄ ⁻·H₂O, crystallizes in the monoclinic system (space group P2₁/n) with the asymmetric unit comprising two formula units (Z′ = 2). All molecular entities are located on general positions. The two crystallographically distinct 4-picolylammonium cations exhibit different conformations. The two unique perchlorate anions are non-disordered, showing an r.m.s. deviation of 0.011 Å from molecular T _d symmetry. The supramolecular structure in the solid state features an intricate tri-periodic network of N—H...O, O—H...N and O—H...O hydrogen bonds.