Metal complexes of the carbonic anhydrase inhibitor methazolamide (Hmacm). Crystal structure of the Zn(macm)2 (NH3)2. Anticonvulsant properties of the Cu(macm)2 (NH3)3(H2O) (2023)

Complexes of nickel(II), and copper(II) were synthesized with pantadentate ligand i.e. 3,3′-thiodipropionicacid-bis(5-amino-1,3,4-thiadiazole-2-thiol) (L). The ligand was synthesized by the condensation of thiodipropionic acid and 5-amino-1,3,4-thiadiazole-2-thiol in 1:2 ratio, respectively. Synthesized ligand was characterized by elemental analysis, mass, ¹H NMR, IR, and molecular modeling. All the complexes were characterized by elemental analysis, molar conductance, magnetic moment, IR, electronic spectra, ESR, and molecular modeling. The newly synthesized complexes possessed general composition [M(L)X₂] where M=Ni(II), Cu(II), L=pantadentate ligand and X=Cl⁻, CH₃COO⁻. The IR spectral data indicated that the ligand behaved as a pantadentate ligand and coordinated to the metal ion through N₂S₃ donor atoms. The molar conductance value of Ni(II), and Cu(II) complexes in DMSO corresponded to their electrolytic behavior. On the basis of spectral study, octahedral and tetragonal geometry was assigned for Ni(II) and Cu(II) complexes, respectively. In vitro fungicidal study of ligand and its complexes was investigated against fungi Candida albicans, Candida parapsilosis, Candidia krusei, and Candida tropicalis by means of well diffusion method.

Five mononuclear ruthenium complexes of the general type trans-[Ru^II(L)(Azo)Cl₂] {(Azo=C₆H₅NNC(COCH₃)NC₆H₄Y, Y=H (1), CH₃ (2), OCH₃ (3), Cl (4), Br (5)} and L is 2-(1,2,3-thiadiazol-4-yl)pyridine have been synthesized and their structures investigated by elemental analyses, spectroscopic (IR, UV/–Vis, and NMR) and electrochemical (cyclic voltammetry) techniques. In addition, complex (3) has been further characterized by X-ray diffraction analysis. The absorption spectrum of 3 in acetonitrile has been modeled by time-dependent density functional theory (TD-DFT) using mixed basis set, LanL2DZ/6–-31+g(d,p), in acetonitrile as a solvent.

The electronic absorption spectra of Schiff base namely 1-[(5-mercapto-[1,3,4]thiadiazol-2-ylimino)-methyl]-naphthalen-2-ol (H₂L) was studied in organic solvents of different polarity as well as in universal buffer solutions of varying pH values at room temperature; the pK_a values were calculated. The effect of Co(II) and Cu(II) ions on the electronic absorption spectra of H₂L was also assigned and the stability constants of the complexes were calculated. The stoichiometry of the metal complexes was determined spectrophotometrically. Solid Co(II) and Cu(II) complexes with H₂L have been synthesized and characterized on the basis of elemental analyses, molar conductance, magnetic susceptibility measurements, IR, electronic as well as ESR spectral studies. The thermal decomposition of the metal complexes was studied by TGA and DTA techniques. The thermo-kinetic parameters; activation energy, pre-exponential factor and entropy of activation were estimated. The interaction between the Schiff base under investigation and the copper nanoparticles in the ground and excited state was considered. The fluorescence quenching rate constant of Schiff base by Cu nanoparticles has a large value.

New benzolamide (H₂bz, 5-phenylsulfonamide-1,3,4-thiadiazole-2-sulfonamide) zinc(II) and copper(II) complexes with tris(2-benzimidazolyl-methylamine) (L) and ammonia are reported. The crystal structures of the Zn(II) complexes were determined. The [Zn(Hbz)L]ClO₄·H₂O compound crystallizes in the triclinic $\text{P}\text{1}\text{̄}$ space group with a=11.006(1), b=14.777(2), c=14.918(2) Å, α=114.30(1), β=98.90(1), γ=107.36(1)° and Z=2. In this compound the Zn(II) has a distorted trigonal bipyramidal geometry. The {[Zn₂(bz)₂(NH₃)₄]·2H₂O}_∞ crystallizes in the monoclinic space group C2/c with a=23.530(3), b=10.4124(11), c=15.428(2) Å, β=110.591(9)° and Z=4. The metal centre is in a distorted tetrahedral [ZnN₄] environment. The benzolamide presents a different coordination behaviour in these complexes. In [Zn(Hbz)L]ClO₄·H₂O it acts as a monodentate ligand through the thiadiazole N atom contiguous to the deprotonated sulfonamido group, while in {[Zn₂(bz)₂(NH₃)₄]·2H₂O}_∞ it behaves as a bridge joining two Zn(II) ions via the N atom of the thiadiazole ring and the N atom of the free sulfonamido group. The Cu(Hbz)L(NO₃) complex was also obtained and characterized. The electronic properties and the EPR of the copper-doped zinc complexes showed that the copper(II) ion adopts a square pyramidal geometry. Also, for the Zn(II) complexes the interaction Zn–benzolamide has been studied using extended-Hückel molecular-orbital (EHMO) calculations.

A new sulfonamide possessing strong carbonic anhydrase (CA) inhibitory properties has been prepared by reaction of 5-amino-1,3,4-thiadiazole-2-sulfonamide with adamantyl-1-carboxylic acid chloride. Metal complexes of the adamantyl derivative, containing di- and trivalent cations, were also obtained and characterized by standard procedures. Although the parent sulfonamide does not possess topical pressure-lowering effects in rabbits when applied as a 2% solution directly into the eye, some of its metal complexes, such as the Zn(II) and Cu(II) derivatives, lower intraocular pressure (IOP) in experimental animals better than dorzolamide, the topical sulfonamide with strong antiglaucoma action, recently introduced in clinical medicine. We propose here that the whole class of metal complexes of heterocyclic sulfonamides (which generally possess much stronger CA inhibitory properties as compared to the original sulfonamides from which they were prepared) might be used for lowering IOP with enhanced efficiencies as compared to those of the simple sulfonamides. Thus, metal complexes of sulfonamides possessing themselves topical antiglaucoma properties might lead to more effective pharmacological agents of this type.

Polyhedron, Volume 85, 2015, pp. 593-597

Two luminescent Cu(I) complexes employing a V-shaped flexible ligand have been prepared, namely {Cu(pbmb)(ClO₄)}_n (1) and {Cu(pbmb)Br}_n (2), [pbmb=1-((2-(pyridine-3-yl)-1H-benzoimidazol-1-yl)methyl)-1H-benzotriazole]. Complex 1 takes on a 2D network architecture and complex 2 features a 1D chain structure, both of which are constructed from a binuclear metallacycle unit. Photoluminescence measurements indicate that with a temperature reduction, the increased lifetimes in the millisecond range and the large stokes shift agree with strong intense phosphorescence emissions for 1 and 2.

Journal of Molecular Liquids, Volume 305, 2020, Article 112819

Currently, about 30% of new approved drugs contained fluorine atoms and most of them are made through fluorination reactions using various kinds of fluorinating reagents. In the current work, we report a facile and more accessible way to probe the fluorination evolution at different stages using a newly developed fluorinating reagent (1-ethyl-3-methylimmidazolium fluoride-ethylene glycol, [C₂C₁im]F-EG). Benzyl bromide was converted to benzyl fluoride using this fluorinating reagent under mild conditions. A more accessible Raman method, compared to NMR, was used to probe the reaction process due to the products having their own characteristic Raman vibrational frequencies because of the formation of different C-X bonds. Thus the yield of the product at different time scales could be then quantified based on their relative intensities, providing a fresh insight into the fluorination process. This method could be applied in other reactions to reflect the important fluorination process, which methodologically reports a facile way to probe reaction processes.

Neuroscience, Volume 393, 2018, pp. 110-122

Cerebral palsy is an irreversible movement disorder resulting from cerebral damage sustained during prenatal or neonatal brain development. As survival outcomes for preterm injury improve, there is increasing need to model ischemic injury at earlier neonatal time-points to better understand the subsequent pathological consequences. Here we demonstrate a novel neonatal ischemic model using focal administration of the potent vasoconstrictor peptide, endothelin-1 (ET-1), in newborn rats. The functional and histopathological outcomes compare favourably to those reported following the widely used hypoxic ischemia (HI) model. These include a robust motor deficit sustained into adulthood and recapitulation of hallmark features of preterm human brain injury, including atrophy of subcortical white matter and periventricular fiber bundles. Compared to procedures involving carotid artery manipulation and periods of hypoxia, the ET-1 ischemia model represents a rapid and technically simplified model more amenable to larger cohorts and with the potential to direct the locus of ischemic damage to specific brain areas.

Materials Today: Proceedings, Volume 5, Issue 8, Part 3, 2018, pp. 16226-16236

This paper describes the formation of self-assembled monolayer of 1-(n-butyl)imidazole (BI) on electrode surface by self-assembly technique. Electrochemical impedance spectroscopy was conducted to establish the optimum concentration and assembling time of the BI SAM for the SAM formation. It was found that the BI monolayer was formed with the concentration of 1.0 mM of BI at 24 h assembling time and the maximum inhibition efficiency that could be attained is 93.2%. The resulting monolayer was characterized by Fourier transform infrared spectroscopy (FT-IR) and energy dispersive X-ray (EDX) analysis. The surface analysis confirmed that the BI molecule was self-assembled on the copper surface. The corrosion resistance ability of the SAM coated copper in 3% NaCl solution was investigated by potentiodynamic polarization studies, cyclic voltammetry, scanning electron microscopy. The result showed that the presence of BI monolayer on copper electrode resulted in better corrosion resistance against copper corrosion in NaCl medium.

European Journal of Medicinal Chemistry, Volume 102, 2015, pp. 487-529

Piperazine is one of the most sought heterocyclics for the development of new drug candidates. This ring can be traced in a number of well established, commercially available drugs. Wide array of pharmacological activities exhibited by piperazine derivatives have made them indispensable anchors for the development of novel therapeutic agents. The review herein highlights the therapeutic significance of piperazine derivatives. Various therapeutically active piperazine derivatives developed by several chemists are reported here.

Journal of Biological Chemistry, Volume 293, Issue 40, 2018, pp. 15497-15512

Acquisition of the trace element copper (Cu) is critical to drive essential eukaryotic processes such as oxidative phosphorylation, iron mobilization, peptide hormone biogenesis, and connective tissue maturation. The Ctr1/Ctr3 family of Cu importers, first discovered in fungi and conserved in mammals, are critical for Cu⁺ movement across the plasma membrane or mobilization from endosomal compartments. Whereas ablation of Ctr1 in mammals is embryonic lethal, and Ctr1 is critical for dietary Cu absorption, cardiac function, and systemic iron distribution, little is known about the intrinsic contribution of Ctr1 for Cu⁺ permeation through membranes or its mechanism of action. Here, we identify three members of a Cu⁺ importer family from the thermophilic fungus Chaetomium thermophilum: Ctr3a and Ctr3b, which function on the plasma membrane, and Ctr2, which likely functions in endosomal Cu mobilization. All three proteins drive Cu and isoelectronic silver (Ag) uptake in cells devoid of Cu⁺ importers. Transport activity depends on signature amino acid motifs that are conserved and essential for all Ctr1/3 transporters. Ctr3a is stable and amenable to purification and was incorporated into liposomes to reconstitute an in vitro Ag⁺ transport assay characterized by stopped-flow spectroscopy. Ctr3a has intrinsic high-affinity metal ion transport activity that closely reflects values determined in vivo, with slow turnover kinetics. Given structural models for mammalian Ctr1, Ctr3a likely functions as a low-efficiency Cu⁺ ion channel. The Ctr1/Ctr3 family may be tuned to import essential yet potentially toxic Cu⁺ ions at a slow rate to meet cellular needs, while minimizing labile intracellular Cu⁺ pools.