Hassan Abul-Futouh

Thiocarbonyl compounds, especially thioketones, have emerged as promising precursors for constructing [FeFe]‐hydrogenase mimics that can mediate hydrogen evolution through both electrochemical and photocatalytic processes. In this work, we report the synthesis of ferrocenyl thioketone‐functionalized triphenylamine and triphenylamine‐(bi)thiophene derivatives as proligands for the assembly of artificial [FeFe]‐hydrogenase active site models. Structural and chemical features of the obtained complexes were elucidated through NMR and IR spectroscopy, elemental analysis, mass spectrometry, and single‐crystal X‐ray diffraction studies. Electrochemical studies using cyclic voltammetry revealed that these architectural mimics efficiently catalyze proton reduction to hydrogen in both the absence and presence of acetic acid (AcOH) as a proton source. Notably, the obtained complexes exhibit less negative reduction potentials than previously reported analogs, suggesting facilitated reduction and improved stabilization of the reduced species.

Several thionated levofloxacin (LVX) derivatives were designed and synthesized to enhance antimicrobial effects. In this study, compounds 2 and 3 (thionated LVX derivatives) were evaluated against bacteria and fungi. Molecular docking was performed for the lead compound and LVX on bacterial topoisomerases. LC–MS analysis was performed to obtain metabolic profiling. Compound 3 exhibited the strongest antibacterial activity against the tested bacterial strains, with a maximum zone of inhibition of 31 mm at 2 mM against Shigella flexneri. Compound 3 was also highly active against Shigella flexneri with an MIC value of 0.0156 µM and an MBC value of 0.0312 µM. Compound 2 lacked antibacterial activity. In addition, compounds 2 and 3 lacked antifungal activity. Molecular docking showed that compound 3 binds favorably to DNA gyrase and DNA topoisomerase IV with the lowest binding energy scores of − 8.54 and − 10.11 kcal/mol, respectively, which were close to LVX scores. LC–MS analysis for the sample prepared following the incubation of K. pneumoniae with compound 3 showed a major peak with retention time at 6.03 min and a protonated molecular ion at m/z 362.15, both of which correspond to LVX standard. LC–MS analysis for compound 3 showed a peak with retention time of 6.40 min and a protonated molecular ion at m/z 377.12. These findings may suggest the biodesulfurization and subsequent activation of compound 3 to LVX, which indicates that compound 3 may act as a prodrug. The presence of sulfur in compound 3 may have enhanced penetration to bacteria and may also do the same for biofilms.

The exceptional catalytic efficiency of [FeFe]-hydrogenases has driven intense efforts to reproduce their structure and function in synthetic models. A key structural feature governing the behavior of synthetic H-cluster analogs lies in the identity of the bridging dithiolato ligands that link the iron centers. These ligands play a pivotal role in tuning the electron density of the metal core, thereby dictating the complex’s redox characteristics and catalytic reactivity. In this context, we herein describe the synthesis and application of ferrocenyl bithiophene-2,2′-yl thioketone (1) as a proligand for assembling biomimetic models of the [FeFe]-hydrogenase active site. The obtained complexes were thoroughly examined using a suite of analytical methods, including NMR and IR spectroscopy, elemental analysis, and a single-crystal X-ray diffraction, affording comprehensive structural and chemical characterization. Furthermore, their electrochemical behavior toward proton reduction and hydrogen evolution was evaluated via cyclic voltammetry, enabling direct comparison with structurally related analogs.

Inspired by the active site of [FeFe]-hydrogenase, we have developed synthetic mimics engineered from the reaction of heteroaryl thioketone derivatives ferrocenyl(5-(4-(diphenylamino)phenyl)thiophen-2-yl)methanethione (PS-Fc-1), ferrocenyl(5′-(4-(diphenylamino)phenyl)-[2,2′-bithiophen]-5-yl)methanethione (PS-Fc-2) and phenyl(5′-(4-(diphenylamino)phenyl)-[2,2′-bithiophen]-5-yl)methanethione (PS-Ph) as pro-ligands with Fe₃(CO)₁₂. The resulting complexes contain thiolato ligands, which enable a close linkage between heteroaryl chromophores and the catalytic center, thereby promoting efficient photocatalytic hydrogen evolution under visible light irradiation. These mimics incorporate a push–pull organic chromophore, consisting of triphenylamine and (bi)thiophene groups, designed to facilitate direct photoexcitation into a charge-separated state. Electrochemical properties were examined using cyclic voltammetry, and photophysical characteristics were determined by steady-state spectroscopy and nanosecond transient absorption supported by (TD-)DFT simulations. Whilst both catalytically active species revealed the formation of charge-separated states directly upon excitation, fast deactivation due to relaxation into low-lying ferrocene-located states prevents the formation of long-lived excited states in the ferrocene-linked dyad. This explains the reduced activity for hydrogen generation of the dyad containing the ferrocene moiety compared to the phenyl one.

In this study, we synthesized a series of PPh₃‐substituted diiron complexes with the general formula [Fe₂(CO)₅PPh₃{μ‐S(CH₂)_nS}] (n = 4 (1), 5 (2), 7 (3), 8 (4)), bearing structural similarities to the active site of [FeFe]‐hydrogenase. These complexes were derived from their parent analogues, [Fe₂(CO)₆{μ‐S(CH₂)_nS}] (n = 4, 5, 7, 8), through ligand substitution. Their formation was verified through a combination of spectroscopic methods, elemental analysis, and X‐ray crystallography, confirming their structural integrity and composition. Moreover, we examined how the PPh₃ ligand and the varying lengths of the dithiolato linker in complexes 1–4 affect their redox properties and catalytic performance. Using cyclic voltammetry, we evaluated their electrochemical behavior and proton reduction activity in the presence of acetic acid (AcOH). Consequently, the reduction potential shifts of complexes 1–4, in comparison to their precursors, followed the sequence: 3 > 2 > 1 > 4. Furthermore, at the highest AcOH concentration established, complex 3 demonstrates the most significant current enhancement (i_cat/i_p = 26.2). In comparison, complexes 1, 2, and 4 exhibit relatively similar i_cat/i_p values of 13.6, 13.0, and 11.9, respectively.

A prominent class of reactions, reductive aminations are used extensively in research labs and industry to synthesize amines; which are applied in a variety of medicines, agrochemicals, and biomolecules. Amine compounds are essential in many aspects of life; amino groups exist in many natural and agricultural products. New 4-(benzylamino)benzoic acid derivatives with general formula of C14H12NO2R, where [R= (H), (4-Cl), (4-NMe), (4-Br), (3-NO2), (4-NO2), (2-OMe), (3-OMe), (4-OMe), (2,3-OMe), (3,4-OMe), (2-OH, 3-OMe), (3-OMe, 4-OH), (3,5-OMe, 4-OH), (2-OH, 5-Br), (3-OH), (4-SMe), (2,3-OH), (3-CF3)] (compounds 1-19) were obtained by reductive amination reaction via reacting p-amino benzoic acid with benzaldehyde derivatives and sodium borohydride. All prepared compounds has been characterized by a variety of spectroscopic techniques (HRMS, FT-IR, 1H, and 13C{1H} NMR) and elemental analysis. Furthermore, the structure of some of the synthesized derivatives were confirmed by single crystal X-ray diffraction (R = 4-Cl, 4-Br, 2-OMe, 3-OMe, 4-OMe, 2,3-OMe), compounds 2, 4, 7-9 and 11, respectively. Moreover, some of these new compounds have shown somehow moderate antibacterial activities against different strains of bacteria (gram-positive and gram-negative) with MIC values ranging from 64-256 µg/ mL. The anticancer activities of all compounds (IC50 values, µM) were evaluated against different cell lines, HGF (Fibroblasts; normal cell line), A549 (Non-Small Cell Lung Cancer cell line) and H69 (Small Cell Lung Cancer cell line). Compound 18 showed a considerable IC50 value of 90.69 against A549 and an excellent value of 32.22 and H69, respectively.