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3-Phenyl-4-methoxybenzaldehyde undergoes condensation with semicarbazide hydrochloride to form a Schiff-base i.e. 3-phenyl-4-methoxybenzaldehyde semicarbazone (abbreviated as MBS). It undergoes complexation with Vanadium(II), Manganese(II), and Copper(II). The comparison of FTIR-spectra of complexes with that of free ligand helps ascertain the coordination points of ligand through the nitrogen of –CH=N– group and oxygen of group. The axial ligands have been varied by chloride, acetate and nitrate ions. The UV/Visible and ESR spectra of complexes predicts their tetragonally distorted octahedral (D4h) symmetry. The tetragonal distortion parameter (Dt) is observed maximum for chloride while it is minimum for nitrate along z-axis. Both vanillin and semicarbazide are established biologically active compounds and hence their biological activities may be enhanced by their complexation and than a versatile field may be developed for further exploration.

The X-ray diffraction study of three compounds containing 2,3-dihydroxybenzaldehyde semicarbazone (H3L1) or 2-hydroxy-3-methoxybenzaldehyde semicarbazone (H2L2) shows the formation of one organic salt with protonated triethylamine [(C2H5)3NH][H2L1]·0.5(CH3)2CO (I) and two new coordination nickel(II) compounds with these two differently substituted semicarbazones of salicylaldehyde [Ni(H3L1)(H2L1)](NO3)·2.5MeOH·0.25H2O (II) and [Ni(H2L2)2]Cl2·4H2O (III) (CIF files CCDC nos. 2041894–2041896 (I–III)). The Ni(II) compounds are ionic and formed by the complex cations with the same metal to ligand ratio. The Ni(II) ion in these complex cations is characterized by a distorted octahedral coordination geometry formed by a set of donor atoms N2O4 of two ligands coordinated via the tridentate mode. In the monocharged complex cation of compound II, two coordinated ligands are not identical. One of them acts as the neutral chelating agent (H3L1), and the second ligand is deprotonated and involved as the monoanion (H2L1)–. Both H2L ligands are neutral in the complex cation of compound III. In the crystal, all the three compounds form supramolecular ensembles of diverse dimensionality and architecture, and their components are joined by weak interactions of different types.

Thiosemicarbazones (TSCNs) constitute a broad family of compounds (R1R2C=N-NH-C(S)- NR3R4), particularly attractive because many of them display some biological activity against a wide range of microorganisms and cancer cells. Their activity can be related to their electronic and structural properties, which offer a rich set of donor atoms for metal coordination and a high electronic delocalization providing different binding modes for biomolecules. Heterocycles such as pyrrole, imidazole and triazole are present in biological molecules such as Vitamine B12 and amino acids and could potentially target multiple biological processes. Considering this, we have explored the chemistry and biological properties of thiosemicarbazones series and their complexes bearing heterocycles such as pyrrole, imidazole, thiazole and triazole. We focus at the chemistry and cytotoxicity of those derivatives to find out the structure activity relationships, and particularly we analyzed those examples with the TSCN units in which the mechanism of action information has been profoundly studied and pathways determined, to promote future studies for heterocycle derivatives.

Heptacoordinated metal complexes with a pentadentate ligand 2,6-diacetylpyridine-bis(thiosemicarbazone) (H2daptsc) were used for the first time ever as building blocks to create polynuclear multifunctional molecular materials. Reactions of the paramagnetic [Mn(II)(H2daptsc)(H2O)2](ClO4)2 and [Mn(II)(H2daptsc)Cl2] complexes with photochromic sodium nitroprusside Na2[Fe(II)(CN)5NO].2H2O were studied. As a result, six polynuclear phases were obtained: {Mn(H2daptsc)Fe(CN)5NO}n·0.5n(MeOH)·0.5n(H2O) (1), {Mn(H2daptsc)Fe(CN)5NO}3n·8n(MeOH) (2), {Mn(H2daptsc)Fe(CN)5NO}2n·n(MeOH)·n(H2O) (3), [Mn(H2daptsc)Cl]2[Fe(CN)5NO] (4), {Mn(H2daptsc)Fe(CN)5NO}n·2n(H2O) (5) and {Mn(H2daptsc)Fe(CN)5NO}n·n(EtOH) (6). The crystal structures of the phases as well as the magnetic and photochromic properties of 1 and 4 were studied.

Two square?planar complexes, [PtLCl] (1) and [PdLCl] (2), were synthesized with quinoline-2-carboxaldehyde thiosemicarbazone ligand (HL), and characterized by IR and NMR spectroscopy and single crystal X-ray diffraction analysis. In both complexes, L- is coordinated tridentately via the same donor atom set, while the fourth coordination site is occupied by a chloride ion. However, the complexes are not isostructural due to different types of non-covalent intermolecular interactions. These interactions were analyzed using Hirshfeld surfaces and two-dimensional fingerprint plots.

By the condensation of thiosemicarbazide with coumarin aldehyde, two novel substituted thiosemicarbazones with chemical formulae C24H25N3O3S (3a) and C26H23N3O3S (3b) have been synthesized. The synthesized compounds were resolved using SC-XRD, and structure elucidation was carried out using 1H NMR, 13C NMR, UV–visible, and FT-IR spectroscopic analyses. Computational calculations at the B3LYP/6-311+G(d,p) level of theory were performed to countercheck the experimental (UV–vis, FT-IR) findings and explore the electronic (FMO, NBO, MEP) properties of 3a–b. The nonlinear optical (NLO) properties of 3a–b were estimated using B3LYP, HF, LC-BLYP, CAM-B3LYP, M062X, and M06 functionals in combination with the 6-311+G(d,p) basis set. The crystallographic data revealed that compounds were crystallized as an orthorhombic crystal lattice with the Pbcn space group and the triclinic crystal lattice with the P̅1 space group. A good concurrence among experimental SC-XRD-generated bond lengths, bond angles, FT-IR, UV–vis, and corresponding DFT results was found, which confirms the purity of both compounds. The NBO analysis confirmed the presence of intramolecular hydrogen bonding and hyperconjugative interactions, which not only were the pivotal cause of stability of the investigated compounds but also led to an overwhelming NLO response. The energy differences calculated for HOMO/LUMO are 3.053 and 3.118 eV in 3a and 3b, respectively. The crystal 3b showed a higher value of first-order polarizability at all levels of theory than 3a. Overall results show that the crystals under investigation are polarized in nature with a good dipole moment. A comparative analysis with urea molecules clearly indicates that the studied compounds are acceptable NLO candidates and they can be used for future technological applications.

2-Oxopropanoic acid reacts in ethanol with N-(prop-2-en-1-yl)hydrazinecarbothioamide in a 1 : 1 mole ratio to form thiosemicarbazone H2L. Coordination compounds Cu(HL)X [X = Cl–, Br–, NO3–], Cu(H2O)(L), Ni(HL)2, Co(HL)2X [X = Cl–, Br–], and Fe(HL)2X [X = NO3–, Br–] are formed in the reactions of H2L with copper(II), nickel(II), cobalt(II), and iron(III) salts. The reactions of Cu(H2O)(L) with imidazole (Im) and 3,4-dimethylpyridine (3,4-Lut) result in mixed-ligand complexes Cu(A)(L) [A = Im, 3,4-Lut]. The structures of two copper complexes were determined by single crystal X-ray diffraction analysis. The synthesized complexes exhibit selective antimicrobial and antifungal activity in the concentration range of 15.62–1000 μg/mL. The introduction of amines into the inner sphere of copper complexes leads to an increase in the antimicrobial activity.

Metal complexes of thiosemicarbazones have been receiving considerable attention in biological applications such as antimicrobial and anticancer therapies. In this work, Co(II), Zn(II) and Mn(II) complexes of 2-hydroxy-5-methoxyacetophenone thiosemicarbazone (HMAT) were synthesized for the first time and characterized by EPR, FT-IR, NMR, UV-Vis spectroscopies, TG/DSC and elemental analysis. X-ray powder diffraction analysis was carried out for Zn(II) complex. HMAT and its Cu(II), Co(II), Zn(II) and Mn(II) complexes were tested as enzyme inhibitory agents. All compounds are effective inhibitor of cytosolic carbonic anhydrase I and II isoforms (hCA I and II) enzymes. IC(50)values of HMAT and its Cu(II), Co(II), Zn(II) and Mn(II) complexes were determined as 93.35, 324.46, 25.67, 1.06 and 22.36 mu M for CA I isozyme and 99.02, 86.64, 57.76, 10.34 and 36.48 mu M for CA II isozyme, respectively. The evaluation of potential cytotoxic effects of the compounds was performed against normal epithelial breast mammary gland CRL-4010, estrogen-positive low metastatic MCF-7 and triple negative highly metastatic MDA-MB-231 breast adenocarcinoma cell lines by MTT assay. The results showed that the tested metal complexes have high cytotoxic effects than their ligand molecule. In particular, the Cu(II) complex displayed preciously high cytotoxic properties different from the others. Given these facts, the Cu(II) complex could be debated as potential chemotherapeutic molecule against drug-resistant breast cancer cells. Minimum inhibitory concentrations of the compounds against the test organisms were also detected for the microbiological analysis., Necmettin Erbakan University Scientific Research Foundation [BAP-161715001], This study was supported by the Necmettin Erbakan University Scientific Research Foundation (BAP-161715001)

Previously, a series of hetareno[e]pyrrole-2,3-diones was found to include compounds with high antimicrobial and antinociceptive activity and low toxicity, so that new hetareno[e]pyrrole-2,3-dione derivatives were expected to have these types of activity. The reactions of pyrrolobenzoxazinetriones with a series of aromatic aldehyde thiosemicarbazones and nicotinic aldehyde thiosemicarbazone are reported. Results from studies of the antinociceptive (hot-plate test) and antimicrobial activity (Staphylococcus aureus No. 906, Escherichia coli No. 1257) are given. The most active compounds were effective on the level of the reference drugs. The target of the antinociceptive activity of the tested compounds was considered nerve endings because signs of central action were not observed in the behavior of animals under the influence of the compounds. The selective antimicrobial activity against Gram-positive bacteria S. aureus was presumably associated with disruption of the cytoplasmic membrane permeability and bacterial RNA synthesis.

A highly selective poly(vinyl chloride) (PVC) membrane electrode based on copper (II) complex of 2-acetylthiophene semicarbazone as a new carrier for iodide-selective electrode is fabricated with t...

Triethylphosphinegold(I) complexes [Au(HL1)P(CH2CH3)3]PF6 (1), [Au(HL2)P(CH2CH3)3]PF6 (2), and [Au(HL3)P(CH2CH3)3]PF6 (3) were obtained with (E)-2-(1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-ylidene)hydrazinecarbothioamide (HL1), (E)-N-methyl-2-(1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-ylidene)hydrazinecarbothioamide (HL2), and (E)-2-(1-(2-methyl-5-nitro-1H-imidazol-1-yl)propan-2-ylidene)-N-phenylhydrazinecarbothioamide (HL3). All compounds were assayed for their cytotoxic activities against HCT-116 colorectal carcinoma cells under normoxia and hypoxia conditions and against nonmalignant HEK-293 human embryonic kidney cells under normoxia conditions. The thiosemicarbazone ligands HL1-HL3 were inactive against HCT-116 cells under hypoxia but while HL3 was inactive, HL1 and HL2 proved to be cytotoxic to both cell lineages under normoxia conditions. Complexes (1-3) and the triethylphosphinegod(I) precursor proved to be active against both cell lineages in normoxia as well as in hypoxia. While 1 and 3 revealed to be active against HEK-293 and HCT-116 cells, being approximately as active against HCT-116 cells in normoxia as under hypoxia, complex (2) proved to be more active against HCT-116 cells under hypoxia than under normoxia conditions, and more active against HCT-116 cells than against the nonmalignant HEK-293 cells, with the selectivity index, calculated as SI = IC50HEK-293/IC50HCT-116hypoxia, equal to 3.7, similar to the value obtained for the control drug tirapazamine (tirapazamine (TPZ), SI = 4). Although the compounds showed distinct cytotoxic activities, the electrochemical behaviors of HL1-HL3 were very similar, as were the behaviors of complexes (1-3). Complex (2) deserves special interest since it was significantly more active under hypoxia than under normoxia conditions. Hence, in this case, selective reduction of the nitro group in a low oxygen pressure environment, resulting in toxic reactive oxygen species (ROS) and damage to DNA or other biomolecules, might operate, while for the remaining compounds, other modes of action probably occur.

Copper (II) complex of the ligand, thiophene-2-aldehyde semicarbazone was synthesized and characterized. Their structures were explored on the basis of CHN analysis, conductance and magnetic susceptibility measurements, spectral studies (FT-infrared and ESI-MS) and thermogravimetric analysis (TGA). It has been observed from spectral and analytical studies, the copper complex have the composition of [CuL(CH3COO)2(H2O)] [where L is thiophene-2-aldehyde semicarbazone]. The electrospray mass spectrum of the ligand and complex exhibited ion at mass-to charge ratio (m/z) of 169.13 and 368.86 matching the calculated values for the molecular ion of the ligand and complex, respectively. One mole of the ligand behaves as bidentate chelating agents around the Cu(II) ion. From conductivity studies, we obtained that the copper complex of the ligand, thiophene-2-aldehyde semicarbazone had no ionic properties. All data confirmed a trigonal bipyramidal geometry of the complex. Antibacterial activity of the compounds against the microbe Enterobacter aerogenes and Bacillus cereus have been screened to reflect that the complex has higher antimicrobial activity than the free ligand.

To synthesize a series of ornidazole thiosemicarbazone analogues on the basis of literature reviews of 2-Methyl-5-nitroimidazoles and thiosemicarbazones and to evaluate all the analogues in vitro for their activity against Aspergillus niger and fumigatus. Thiosemicarbazone analogues were synthesized from oxidising ornidazole with potassium dichromate and refluxing the oxidised product with substituted thiosemicarbazide using ethanol as solvent in the acidic medium overnight. All the synthesized analogues of ornidazole showed good antifungal action against fumigatus and niger except compound C-4. Unsubstituted amine analogue C-2 has shown highest percentage inhibition (96.6%, 500 μg/ml) against fumigatus while aromatic amine with or without electronegative atom analogues C-3 and C-5 has shown highest activity against Aspergillus niger which is two times than standard drug ornidazole (100%, 1000 μg/ml).

Two new copper(II) complexes of pyridine-2-carboxaldehyde-N-(2-pyridyl)hydrazone [Cu(PCPH)(H2O)2](NO3)(H2O)2 (1) and 2-hydroxy-1-naphthaldehyde-semicarbazone [Cu(II)(HNSC)H2O]·NO3·H2O (2) have been synthesized and characterized by spectroscopic techniques and single crystal X-ray diffraction study. Complex 1 crystallized as square pyramidal coordination complex in triclinic crystal system while complex 2 crystallized as square planar complex in monoclinic crystal system. EPR spectral patterns are of normal order of energy levels, i.e. x2-y2 >> z2 > xy > xz, yz, with partial covalent character. Both copper(II) complexes were found to be groove binding to calf-thymus DNA and showed activity against E. coli, S. aureus, B. cereus and E. faccium.

Thiosemicarbazones have been the focus of scientists owing to their broad clinical anticancer range. Herein, A Series of new thiosemicarbazone derivatives 5-9 were synthesized and confirmed through the use of different spectroscopic techniques along with elemental analysis. The in vitro cytotoxic activity of compounds 5-9 against MCF-7 and A549 cell lines and normal breast cells were assessed. Several compounds were found to be active. The most active compound 7 caused MCF-7 cell cycle arrest at G1/ S phases; and induced apoptosis at the pre-G1 phase. The apoptosis-inducing activity of compound 7 was proofed by the elevation of caspase 3/7 activity and also by up-regulation of the expression of Bax and p53 proteins together with the down-regulation of the expression of the Bcl-2 protein. It also had a strong inhibitory effect topoisomerase IIβ enzyme. Molecular Docking study revealed that the synthesized compounds had good docking scores compared to the standard drug Etoposide towards the topoisomerase IIβ protein (3QX3). Overall, these findings confirmed that the new thiosemicarbazone derivatives could aid in the development of promising cancer drug candidates.

MAO-B inhibitors are frequently used in the treatment of neurodegenerative diseases such as Parkinson’s and Alzheimer’s. Due to the limited number of compounds available in this field, there is a need to develop new compounds. In the recent works, it was shown that various thiosemicarbazone derivatives show hMAO inhibitory activity in the range of micromolar concentration. It is thought that benzofuran and benzothiophene structures may mimic structures such as indane and indanone, which are frequently found in the structures of such inhibitors. Based on this view, new benzofuran/benzothiophene and thiosemicarbazone hybrid compounds were synthesized, characterized and screened for their hMAO-A and hMAO-B inhibitory activity by an in vitro fluorometric method. The compounds including methoxyethyl substituent (2b and 2h) were found to be the most effective agents in the series against MAO-B enzyme with the IC50 value of 0.042 ± 0.002 µM and 0.056 ± 0.002 µM, respectively. The mechanism of hMAO-B inhibition of compounds 2b and 2h was investigated by Lineweaver–Burk graphics. Compounds 2b and 2h were reversible and non-competitive inhibitors with similar inhibition features as the substrates. The Ki values of compounds 2b and 2h were calculated as 0.035 µM and 0.046 µM, respectively, with the help of secondary plots. The docking study of compound 2b and 2h revealed that there is a strong interaction between the active sites of hMAO-B and analyzed compound.

Diabetes mellitus (DM) is chronic and metabolic disorder, which is mainly attributed by hyperglycemia. Vanadium salts and their oxo-complexes have been shown to possess insulin-mimetic and anti-diabetic activities in animal models and diabetic patients. The main goal of this study was to investigate the protective effect of oxovanadium(IV) complex based on thiosemicarbazone (VOL) [L: (N(1)-2,4-dihydroxybenzylidene-N-(4)-2-hydroxybenzylidene-S-methyl-isothiosemicarbazidato-oxovanadium(IV)] on glycoprotein components levels and oxidative lung injury of streptozotocin (STZ)-induced diabetic rats. Male Swiss albino rats were separated into four groups. Group I (

In the present study, acridine-thiosemicarbazones (ATD) derivatives were tested for their interaction properties with BSA through UV–Vis absorption and fluorescence spectroscopic studies. Both hyperchromic and hypochromic effects, as well as red or blue shifts were demonstrated after the derivatives were added to the BSA. Values for the binding constant (Kb) ranged from 1.62 × 104 to 8.71 × 105 M−1 and quenching constant (KSV) from 3.46 × 102 to 7.83 × 103 M−1 indicating a good affinity to BSA protein. Complementary, two compounds were selected to assess their inhibition activity against topoisomerase IIα enzyme, of which derivative 3a presented the best result. Moreover, to evaluate protein-ligand interactions, as well as the antitopoisomerase potential of these compounds, tests of molecular modeling were performed between all compounds using the albumin and Topoisomerase IIα/DNA complex. Finally, in silico studies showed that all derivatives used in this research displayed good oral bioavailability potential.

3-methoxysalicylidene N-alkyl-thiosemicarbazones (L) (where alkyl is propyl, butyl, pentyl or hexyl) were synthesized. The reaction of the ONS donor ligands with [MoO2(acac)2] in methanol yielded the mixed ligand complexes bearing a solvent molecule as co-ligand, [MoO2(L)MeOH)]. The ligands and complexes were characterized by using analytical and spectroscopic methods. As a representative sample, the dioxomolybdenum(VI) complex of the N4-butyl-substituted thiosemicarbazone was crystallographically examined to ensure the expected structures. X-ray data showed a distorted octahedral environment of molybdenum center. Tyrosinase, collagenase inhibition and antioxidant properties of the compounds were investigated using spectroscopic methods. The ligand and complexes exhibited the different inhibitory activities depending on N-alkyl substituents. Similarly, also the antioxidant capacity of the compounds changed in relation to the substituents.

In the crystalline state, salicyl­aldehyde N(4)-morpholino­thio­semicarbazone forms sheets parallel to (002) and consisting of two parallel chains running in the a-axis direction and formed by N—H⋯O and C—H⋯O hydrogen bonds., The structure of the title compound (systematic name: N-{[(2-hy­droxy­phen­yl)methyl­idene]amino}­morpholine-4-carbo­thio­amide), C12H15N3O2S, was prev­iously determined (Koo et al., 1977 ▸) using multiple-film equi-inclination Weissenberg data, but has been redetermined with higher precision to explore its conformation and the hydrogen-bonding patterns and supra­molecular inter­actions. The mol­ecular structure shows intra­molecular O—H⋯N and C—H⋯S inter­actions. The configuration of the C=N bond is E. The mol­ecule is slightly twisted about the central N—N bond. The best planes through the phenyl ring and the morpholino ring make an angle of 43.44 (17)°. In the crystal, the mol­ecules are connected into chains by N—H⋯O and C—H⋯O hydrogen bonds, which combine to generate sheets lying parallel to (002). The most prominent contribution to the surface contacts are H⋯H contacts (51.6%), as concluded from a Hirshfeld surface analysis.

New and efficient synthetic approaches to phenothiazine derivatives have been developed on the basis of reactions of 1-(10H-phenothiazin-2-yl)ethanone hydrazone with isothiocyanates and hydrazonoyl chlorides under conventional thermal heating and microwave irradiation. The structures of the newly synthesized compounds have been confirmed by elemental analyses and spectroscopic data.

Novel spiro(3-hydroxy-5,5-dimethyl)-1,5’-(2’-substituated[1,3,4]-oxadiazole/thiadiazolo[3,2-c] thiazolines and 3-hydroxy-5,5-dimethyl-spiro[cyclohex-2-ene-thiazolo/thiazino[3,2-b]-s-tetrazine were prepared from previously reported hydrazone, semicarbazone, carbazone, and spiro-s-tetrazine intermediates derived from dimedone precursor. All the newly synthesized heterocycles have been characterized by analytical and spectral (1H NMR and hC NMR) data and screened their in vitro antibacterial activity against gram negative bacteria Escherichia coli and gram positive bacteria Staphylococcus aureus. Some of the compounds showed moderate to good activities towards the bacteria chosen.

Two series of novel aryl-acrylic derivatives were designed, synthesized, and screened in enzymatic and cellular inhibitory activities. All compounds showed moderate to significant potency. The SAR analyses indicated that the semicarbazone linker is better than the 1,2,3-triazole linker. Among semicarbazone compounds that R1 bearing di-chain amino groups exhibited superior activities to those with morpholino group. Furthermore, compounds with electron-withdrawing groups at the 2-position or 4-position on the terminal phenyl ring were more active. Among these, compounds 7g, 7i, 7m and 7n exhibited the inhibitory potency in the low micromolar range and displayed negligible level of cytotoxicity against normal HeLa cells. In addition, the study suggested that the aryl-acrylic is an interesting novel scaffold for IDO1 inhibition for further development.

4-[bis(2-chloroethyl)amino]benzaldehyde-N(4)-phenyl-thiosemicarbazone (1), 4-[bis(2-chloroethyl)amino]benzaldehyde-N(4)-para-chloro-phenyl-thiosemicarbazone (2), 4-[bis(2-chloroethyl)amino]benzaldehyde-N(4)-methyl-thiosemicarbazone (3) and 4-[bis(2-chloroethyl)amino]benzaldehyde-benzoylhydrazone (4) were obtained by functionalization of the bis(2-chloroethyl)amino DNA alkylating group with a thiosemicarbazone/hydrazone moiety. The compounds were fully characterized by means of their infrared (including theoretical vibrational analyses) and NMR spectra, as well as by means of X-ray crystal structure determinations. When assayed on a panel of different tumor cells only (1) exhibited cytotoxic effects on B16F10 melanoma cells (IC50 = 17.1 ± 3.1 μM). A cell viability assay on melanoma cells revealed that while (1) had cytotoxic effects on B16F10 and A2058 cells, the structure-related hydrazone (4) was devoid of activity. In addition, (1) was capable to reduce viability of melanoma cells without affecting the viability of non-malignant human endothelial cells (HUVEC), suggesting that this compound or its analogues could be further investigated as potential antimelanoma drug candidates. Preliminary investigation on the mode of action of (1) indicated that the compound induces cell death by necrosis. Theoretical calculations showed that in all compounds (1–4) the reactivities of the N-mustard pharmacophoric group towards dehalogenation are similar. In addition, theoretical studies suggested that the nucleophilicities of the mustard group are very similar in (1–4). Hence, all compounds (1–4) might be expected to exhibit comparable reactivity, and the differences in biological activity among the compounds may not be attributed to variances in reactivity at the N-mustard group.

Synthesis of 1-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-1 H -indole- -2,3-dione ( 10 ) was achieved by coupling 1 H -indole-2,3-dione ( 16 ) with ( R )- -(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate ( 15 ) in the presence of sodium hydride in dry N , N -dimethylformamide at room tempe­ra­ture in a closed Erlenmeyer flask. Condensation of 10 with hydrazinecarbo­thioamide in water afforded the thiosemicarbazone derivative 17 ; its sub­sequent cyclization with potassium carbonate in water gave the corresponding thione 18 in good yield. The 3-allylthio and 3-benzylthio derivatives 20 and 21 were also prepared by alkylating thiol 19 with alkyl halides in aqueous sodium hydroxide or coupling of 3-(allylthio/benzylthio)-5 H -1,2,4-triazi­no[5,6- b ]indoles ( 23 and 24 ) with compound 15 in NaH/DMF. Compound 20 was isomerized to a mixture of geometrical isomers ( E / Z )-5-[(2,2-dimethyl-1,3-dioxolan-4-yl)­methyl]-3-(prop-1-en-1-ylthio)-5 H -1,2,4-triazino[5,6- b ]indoles ( 25 and 26 ), evi­denced by their 1H- and 13C-NMR spectra taken in deuterodimethyl sul­foxide. Structural elucidation of the synthesized compounds was realized using FT-IR, 1H-NMR, 13C-NMR, mass spectrometry and elemental analysis. The newly synthesized compounds were found to possess moderate inhibitory act­ivity against the fungus Candida albicans compared to clotrimazole as refer­ence control. Compounds 10 , 17 , 19 , 20 , 21 , 23 and 24 had mean growth inhibition zones ( IZ ) and minimal inhibitory concentrations ( MIC ) in the range of 12–15 mm and 31.25–200 μg mL-1, respectively, with inhibition levels in the range 70.58–88.23 %. Compound 19 exhibited moderate activity against Gram-posi­tive bacteria Staphylococcus aureus relative to imipenem as the stan­dard drug. All compounds were inactive against Escherichia coli and Pseudo­monas aeru­ginosa .

Azapeptides represent a class of peptidomimetics and exhibit important utilizations in drug discovery. Diversity-oriented synthesis of azapeptides is challenging due to the complexity of hydrazine chemistry and peptide coupling. Here we report an improved procedure of submonomer azapeptide synthesis by selective alkylation of semicarbazone using various alcohols mediated by the Mitsunobu reaction. The effectiveness of this new strategy was further proved by synthesizing a series of azapeptidomimetics of angiotensin 1–7.

Peptides are commonly perceived as inapplicable components for construction of porous structures. Due to their flexibility the design is difficult and shape persistence of such putative structures is diminished. Notwithstanding these limitations, the advantages of peptides as building blocks are numerous: they are functional and functionalizable, widely available, diverse and biocompatible. We aimed at the construction of discrete porous structures that exploit the inherent functionality of peptides by an approach that is inspired by nature: structural pockets are defined by the backbones of peptides while functionality is introduced by their side chains. In this work peptide ribbons were preorganized on a macrocyclic scaffold using azapeptide-aldehyde reactions. The resulting cavitands with semicarbazone linkers arrange the peptide backbones at positions that are suitable for self-assembly of dimeric capsules by formation of binding motifs that resemble eight-stranded β-barrels. Self-assembly properties and inside/outside positions of the side chains depend crucially on the chirality of peptides. By rational optimization of successive generations of capsules we have found that azapeptides containing three amino acids in a (l, d, d) sequence give well-defined dimeric capsules with side chains inside their cavities. Taking advantage of the reversibility of the reaction of semicarbazone formation we have also employed the dynamic covalent chemistry (DCC) for a combinatorial discovery of capsules that could not be rationally designed. Indeed, the results show that stable capsules with side chains positioned internally can be obtained even for shorter sequences but only for combination peptides of (l, l) and (d, l) chirality. The hybrid (l, l)(d, l) capsule is amplified directly from a reaction mixture containing two different peptides. All capsules gain substantial ordering upon self-assembly, which is manifested by a two orders of magnitude increase of the intensity of CD spectra of capsules compared with non-assembled analogs. Temperature-dependent CD measurements indicate that the capsules remain stable over the entire temperature range tested (20-100 °C). Circular dichroism coupled with TD DFT calculations, DOSY measurements and X-ray crystallography allow for elucidation of the structures in the solid state and in solution and guide their iterative evolution for the current goals.

Equimolar reaction of copper(I) iodide with PPh3 in acetonitrile formed compound of empirical composition, {CuI(Ph3P)} and its further reaction in chloroform with pyridine-2-carbaldehyde-N-methyl thiosemicarbazone {(C5H4N)HC2 N3-N2-(H)-C1( S)N1HR; R = Me; HL1-Me} formed crystals of complex, [CuICl(Ph3P)(κS1-H2L1-Me] 1a, tetramer [Cu4I4(Ph3P)4] 1b and free HL1-Me 1c, separated from the same reaction vessel. The formation of product 1a involved abstraction of chlorine from chloroform and has pyridine-N-protonated thio-ligand. Copper(I) bromide/chloride with Ph3P and HL1-Me or HL1-Et also formed pyridyl protonated, [CuBr2(Ph3P)(κS1-H2L1-Me)] 2, [CuCl2(Ph3P)(κS1-H2L1-Me)] 3, [CuBr2(Ph3P)(κS1-H2L1-Et)] 4 and [CuCl2(Ph3P)(κS1-H2L1-Et)] 5. The products similar to 1b and 1c were also identified in these reactions. In these four coordinated complexes the pyridine protonated thio-ligands are coordinating through sulfur only. Copper(I) halides with benzaldehyde-N1-substituted thiosemicarbazones {(C6H5)HC2 N3-N2(H)-C1( S)-N1HR; R = Me, Et; HL2-Me; HL2-Et} and Ph3P have yielded halogen bridged dinuclear complexes, [Cu2(μ-X)2(κS1-HL2-R)2(Ph3P)2] (X, R: I, Me, 6; Br, Me, 7; I, Et, 8; Br, Et, 9; Cl, Et, 10). For R = phenyl at N1 atom, copper(I) halides with two m moles of HL2-Ph have formed sulfur–bridged dinucelar complexes, namely, [Cu2(μ-S-HL2-Ph)2(κS1-HL2-Ph)2X2] (X = I, 11, Br, 12, Cl, 13). Complexes have been characterized using analytical data, IR, proton NMR and single crystal X-ray crystallography (1–5, 7, 9, 11 and 12). The coordination environment of the Cu in complex 1a contains both Cl and I, but both sites are disordered.

Some biologically active semicarbazone-triazole hybrid molecules have been designed and synthesized from semicarbazone linked terminal alkyne and aromatic azides via Cu(I)-catalyzed cycloaddition reactions. All newly synthesized compounds were successfully characterized by using IR, 1H-NMR, 13C-NMR, and HRMS spectral techniques. The synthesized molecules were screened in vitro for anti-bactericidal effects on E. coli (MTCC 16521), B. subtilis (MTCC441), S. aureus (MTCC 3160), P. aeruginosa (MTCC 424) and S. epidermidis (MTCC 6880). The antibacterial property results revealed that the semicarbazone-triazole hybrid molecules (9b, 9e, and 9f) are a better alternative to the existing antibacterial drug ciprofloxacin. The docking study on the most active compound 9b and its alkyne precursor 8 with the DNA gyrase enzyme of E. coli bacteria supported the biological activity results.

Solvent-, acidity-, and redox-responsive thione(thiol)-disulfide interconversion were achieved by a dinuclear copper(ii) complex bearing a bis(thiosemicarbazone) (bTSC) ligand. The role of copper(ii) ion coordination was rationalized by parallel comparison with a bare bTSC ligand and zinc(ii) bTSC complexes under identical reaction conditions.

A new series of N-(4)-substituted thiosemicarbazone derivatives 4-8 incorporating a benzo[d][1,3]dioxole moiety were synthesized through the reaction of N-(4)-(benzo[d][1,3]dioxol-5-yl)-thiosemicarbazide with various carbonyl compounds such as aromatic aldehyde, heterocyclic aldehyde, acetophenone, heterocyclic ketone and cyclic ketone derivatives. The structure of the prepared thiosemicarbazones was established based on spectroscopic IR, 1H-NMR, 13C-NMR and elemental analyses data. The antiviral activity of the synthesized compounds was tested against Bovine Viral Diarrhea Virus (BVDV).

A series of six sulfur-bridged dinuclear silver(I) thiosemicarbazone complexes were synthesized through the reaction of silver(I) nitrate with 4-phenyl-3-thiosemicarbazone derivatives together with triphenylphosphine (PPh3) (in a 1:1:2 molar ratio). Following structural characterizations using various techniques such as elemental analysis, Fourier-transform infrared (FTIR) spectroscopy, as well as 1H, 13C, 31P{1H}s, COSY, and 1H-13C nuclear magnetic resonance (NMR) spectroscopy, it was found that the thiosemicarbazone ligand exists in the form of a thione rather than thiol tautomer. Subsequently, MDA-MB-231 and MCF-7 breast cancer cell lines, as well as the HT-29 colon cancer cell lines, were used to investigate the in vitro antiproliferative activities of these complexes. In all cases, the IC50 values were in the potent micromolar range. Besides, the aforementioned complexes also had good antiplasmodial activity against chloroquine-resistant P. falciparum, as per the results of histidine-rich protein 2 (HRP2) assays and cytotoxicity evaluations of MDBK cells.

The central role of iron in tumor progression and metastasis motivates the development of iron-binding approaches in cancer chemotherapy. Disulfide-based prochelators are reductively activated upon cellular uptake to liberate thiol chelators responsible for iron sequestration. Herein, a trimethyl thiosemicarbazone moiety and the imidazole-2-thione heterocycle are incorporated in this prochelator design. Iron binding of the corresponding tridentate chelators leads to the stabilization of a low-spin ferric center in 2 : 1 ligand-to-metal complexes. Native mass spectrometry experiments show that the prochelators form stable disulfide conjugates with bovine serum albumin, thus affording novel bioconjugate prochelator systems. Antiproliferative activities at sub-micromolar levels are recorded in a panel of breast, ovarian and colorectal cancer cells, along with significantly lower activity in normal fibroblasts.

The use of N,S chelating ligands such as thiosemicarbazides and dithiocarbazates provides an excellent environment to complex transition metals in a variety of oxidation states. Ligands of this sort initially prompted research in the medical field for their anti-cancer activity. However, it was later realised their ability to complex metals for use in other applications was far more extensive.Complexes of Cu(III) and Ni(III) are rare (compared to Cu(II) and Ni(II)) and are not often isolated as stable entities, but have been proposed as transient intermediates in some reactions. The general requirements for stabilising high oxidation states stem from the nature of the donor atoms, the degree of electron delocalisation, the size of the chelate rings, the use of electron donating groups and the formal charge on the ligand to balance the high charge of the metal ion.Combining the b-diketone acetylacetone with 2 equivalents of the relevant thiosemicarbazide or dithiocarbazate produces a tetradentate N2S2 ligand that is suitable for stabilising high oxidation states according to the above specifications. These two families, acetylacetone bis(thiosemicarbazone) and acetylacetone bis(dithiocarbazate) Schiff bases, were investigated here in complex with Cu and Ni.The Ni(II) coordination chemistry with the acetylacetone bis(thiosemicarbazone) ligands was studied and two linkage isomers were observed to form; a symmetric and an asymmetric species, in the absence of oxygen. Exposure to air led to the symmetric Ni(II) isomer undergoing ligand oxidation with a ketone group installed on the acetylacetone backbone. The explanation for this phenomenon was linked with the redox-activity of the ligand.The Cu(II) coordination chemistry found only symmetric coordination of the acetylacetone bis(thiosemicarbazone) ligands and again ligand oxidation to the ketone derivative was seen. In this case a Cu(II) intermediate (most likely bearing a ligand centred radical) was identified using a combination of spectroelectrochemistry, voltammetry and time-resolved UV-Vis spectroscopy.The findings were extended to investigating the copper and nickel complexes of the analogous benzoylacetone bis(thiosemicarbazones) to explore the mix of electron donating and electron withdrawing features on the acetylacetone moiety, along with the presence of a bulky substituent to see if this directed the coordination or reactivity of the complex.Finally, investigating acetylacetone bis(dithiocarbazate) Schiff base complexes of nickel and copper revealed a major effect upon exchanging the non-coordinating terminal nitrogen of a thiosemicarbazone with a sulfur of a dithiocarbazate. In this case, both Cu(III) and Ni(III) complexes were isolated and structurally characterised. This produced surprisingly significant differences that may be the key to understanding why high oxidation states are more often seen with ligands of acetylacetone bis(dithiocarbazate) Schiff bases than acetylacetone bis(thiosemicarbazones).

Azapeptides contain at least one aza-amino acid, where the α-carbon has been replaced by a nitrogen atom, and have found broad applicability in fields ranging from medicinal chemistry to biomaterials. In this chapter, we provide a step-by-step protocol for the solid phase submonomer synthesis of azapeptides, which includes three steps: (1) hydrazone activation and coupling onto a resin-bound peptide, (2) chemoselective semicarbazone functionalization for installation of the aza-amino acid side chain, and (3) orthogonal deprotection of the semicarbazone to complete the monomer addition cycle. We focus on semicarbazone functionalization by N-alkylation with primary alkyl halides, and describe conditions for coupling onto aza-amino acids. Such divergent methods accelerate the synthesis of peptidomimetics and allow the rapid introduction of a wide variety of natural and unnatural side chains directly on solid support using easily accessible submonomers.

In this study, eight new Schiff base derivatives (2a-h) were synthesized and their inhibition activities against Acetylcholinesterase (AChE), Butyrylcholinesterase (BChE), α-Glucosidase and Lactoperoxidase (LPO) were investigated. Structures of the synthesized compounds were characterized using 1H and 13C nuclear magnetic resonance (NMR), infrared spectroscopy (IR), and high-resolution mass spectrometry (HRMS) spectroscopic methods. AChE was inhibited by these novel Schiff bases (2a-h) in low nanomolar levels, the Ki of which differed between 592.66 ± 57.04 and 810.78 ± 84.06 nM. Against BChE, the novel compounds demonstrated Kis varying from 358.31 ± 37.88 to 577.24 ± 59.91 nM. Also, these novel Schiff bases effectively inhibited α-glucosidase, with Ki values in the range of 1.56 ± 0.32 to 14.78 ± 2.57 nM. For LPO, Ki values were in the range of 3.96 ± 0.37 to 12.75 ± 0.06 nM. For α-glucosidase, the most effective molecules were 2b and 2 g with Ki values of 1.56 ± 0.32 and 14.78 ± 2.57 nM, respectively. Molecular docking results showed that the compounds have binding affinity with -5.559, -9.698, -7.606, and -6.971 kcal/mol against LPO, AChE, BChE, and α-glucosidase enzyme, respectively. It has been observed that the furan and thiosemicarbazone moieties play an important role in the inhibition of these enzymes.

This chapter describes a method to assay the activity of reactive intermediate deaminases (Rid), a large family of conserved soluble enzymes, which have been proposed to prevent damages from metabolic intermediates such as the highly reactive and unstable compounds enamines/imines. In this method, the flavin adenine dinucleotide-dependent L- or D-amino acid oxidases generate an imino acid starting from a L- or D- amino acid, respectively. This reaction is coupled to the hydrolysis of the imino acid to the corresponding α-keto acid and ammonium ion catalyzed by a Rid enzyme. The spectrophotometric assay consists of measuring the decrease of the initial rate of formation of the semicarbazone, derived from the spontaneous reaction of the imino acid and semicarbazide, caused by the presence of the Rid enzyme. The set-up and testing of this method imply a preliminary characterization of the ability of the amino acid oxidase to release the imino acid required for the subsequent reactions. To this purpose, the activity of the L- or D-amino acid oxidases with different amino acids can be measured as production of hydrogen peroxide or formation of semicarbazone in parallel assays. The advantages and limitations of this assay of Rid activity are discussed.

A set of 12 monosubstituted acetophenone thiosemicarbazone derivatives (TSCs) were synthesized and their inhibitory properties toward tyrosinase activity were tested. Moreover, their ability to inhibit melanogenesis in the B16F10 murine melanoma cell line was studied. In order to investigate the nature of interactions between the enzyme and the inhibitors, molecular docking to the active site was performed. TSCs 5, 6, 8, and 9 revealed a half maximal inhibitory concentration (IC50) below 1 &micro, M. Compound 6 turned out to be the most potent tyrosinase inhibitor. All investigated compounds showed reversible inhibition of competitive or mixed type. The para-substituted TSCs had higher affinity for the enzyme as compared to their ortho- and meta-analogues. All investigated compounds inhibited melanin production in B16F10 cells at the micromolar level. Molecular docking showed that the sulfur atom of the thiourea moiety penetrates the active site and interacts with copper ions. The above outcomes might be helpful in the design of new tyrosinase inhibitors in the food and cosmetic industries.

Two new polyoxometalate (POM)-based hybrid compounds modified by a Schiff base, [Fe(DAPSC)(H2 O)2 ]2 [HPMo2 V Mo10 VI O40 ] ⋅ 5H2 O (1) and [Fe(DAPSC)(H2 O)]2 [HPV3 IV Mo4 V Mo7 VI O42 ] ⋅ 6H2 O (2), (DAPSC=2,6-diacetylpyridine bis-(semicarbazone)), have been successfully constructed from typical Keggin POMs, iron ions, and DAPSC ligands under hydrothermal condition. Structural analysis demonstrates that the Fe-Schiff base ligand units are free from polyacid anions in compound 1. While in compound 2, the Fe-Schiff base ligand units are bridged with polyacid anions via Fe-O bonds to emerge a stable double-supported skeleton. Noticeably, owing to the introduction of vanadium in H5 PMo10 V2 O40 ⋅ 32.5H2 O, a divanadium-capped configuration is shaped in compound 2. Besides, the third-order nonlinear optical (NLO) properties of two compounds were explored. It should be noted that both compounds 1 and 2 have two-photon absorption properties, which indicates that the two compounds are potential nonlinear optical materials.

The synthesis of palladium cyclometallated compounds with thiosemicarbazone ligands is described,as well as their reactivity with bidentate phosphine ligands. The synthesis of the ligands is carried out by a condensation reaction between a ketone and a thiosemicarbazide. Subsequently, metallation proceeds, and the resulting product is reacted with the bis(diphenylphosphino)methane (dppm) using the appropriate conditions to obtain the compound with phosphine in a monodentate coordination mode.

The present work reports the synthesis and structural elucidation of six novel copper(II) complexes with 2-acetylpyridine semicarbazone (HL1) and 2-acetylpyridine N(4)-phenyl semicarbazone (HL2). In all compounds, the semicarbazone ligands were find tridentate with NNO-donor atoms. The single crystal X-ray diffraction analysis showed the influences of the different copper salt starting reagent in the crystal structures. A packing architectures analysis has been undertaken to delineate the role of relevant noncovalent interactions. The π···π stacking interactions and hydrogen bonds were analyzed using the Hirshfeld surface and fingerprint plots. In addition, the compounds were also characterized by physicochemical and spectroscopic methods. A new ligand and six copper(II) complexes of semicarbazone derivatives have been synthesized and their crystal structures have been studied. Spectroscopy experiments and Hirshfeld Surface were analyzed.

Inhibition of β-amyloid peptide (Αβ) aggregation in Alzheimer's disease (AD) is among the therapeutic approaches against AD which still attracts scientific research interest. In the search for compounds that interact with Aβ and disrupt its typical aggregation course toward oligomeric or polymeric toxic assemblies, small organic molecules of natural origin, combining low molecular weight (necessary blood-brain barrier penetration) and low toxicity (necessary for pharmacological application), are greatly sought after. Isatin (1

usc This paper reports the oxidation of inulin using varying ratios of sodium periodate and the characterization of the inulin polyaldehyde. The physicochemical properties of the inulin polyaldehyde (oxidized inulin) were characterized using different techniques including 1D NMR spectroscopy, 13C Nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), differential scanning calorimetric (DSC), ultraviolet-visible spectroscopy (UV), and scanning electron microscopy (SEM). The aldehyde peak was not very visible in the FTIR, because the aldehyde functional group exists in a masked form (hemiacetal). The thermal stability of the oxidized inulin decreased with the increasing oxidation degree. The smooth spherical shape of raw inulin was destructed due to the oxidation, as confirmed by the SEM result. The 1HNMR results show some new peaks from 4.8 to 5.0 as well as around 5.63 ppm. However, no aldehyde peak was found around 9.7 ppm. This can be attributed to the hemiacetal. The reaction of oxidized inulin with tert-butyl carbazate produced a carbazone conjugate. There was clear evidence of decreased peak intensity for the proton belonging to the hemiacetal group. This clearly shows that not all of the hemiacetal group can be reverted by carbazate. In conclusion, this work provides vital information as regards changes in the physicochemical properties of the oxidized inulin, which has direct implications when considering the further utilization of this biomaterial. Refereed/Peer-reviewed

A series of novel steroidal 5&alpha, 8&alpha, endoperoxide derivatives bearing semicarbazone (7a&ndash, g) or thiosemicarbazone (7h&ndash, k) side chain were designed, synthesized and evaluated for their cytotoxicities in four human cancer cell lines (HepG2, HCT-116, MCF-7, and A549) using the MTT assay in vitro. The results showed that compound 7j exhibited significant cytotoxic activity against HepG2 cells (IC50 = 3.52 &mu, M), being more potent than ergosterol peroxide. Further cellular mechanism studies in HepG2 cells indicated that compound 7j triggered the mitochondrial-mediated apoptosis by decreasing mitochondrial membrane potential (MMP), which was associated with up-regulation of Bax, down-regulation of Bcl-2, activation levels of the caspase cascade, and formation of reactive oxygen species (ROS). The above findings indicated that compound 7j may be used as a promising skeleton for antitumor agents with improved efficacy.

ChemBioChem 21, 1 - 12 (2020). doi:10.1002/cbic.202000564, Three chiral tridentate N^N^S coordinating pyridine‐carbaldehyde (S)‐N4‐(α‐methylbenzyl)thiosemicarbazones (HTSCmB) were synthesised along with lysine‐modified derivatives. One of them was selected and covalently conjugated to the cell‐penetrating peptide sC18 by solid‐phase peptide synthesis. The HTSCmB model ligands, the HTSCLp derivatives and the peptide conjugate rapidly and quantitatively form very stable Pt$^{II}$ chlorido complexes [Pt(TSC)Cl] when treated with K$_2$PtCl$_4$ in solution. The Pt(CN) derivatives were obtained from one TSCmB model complex and the peptide conjugate complex through Cl$^−$→CN$^−$ exchange. Ligands and complexes were characterised by NMR, IR spectroscopy, HR‐ESI‐MS and single‐crystal XRD. Intriguingly, no decrease in cell viability was observed when testing the biological activity of the lysine‐tagged HdpyTSCLp, its sC18 conjugate HdpyTSCL‐sC18 or the PtCl and Pt(CN) conjugate complexes in three different cell lines. Thus, given the facile and effective preparation of such Pt‐TSC‐peptide conjugates, these systems might pave the way for future use in late‐stage labelling with Pt radionuclides and application in nuclear medicine., Published by Wiley-VCH, Weinheim

Synthesis, characterization, coordination, bonding and electronic behavior of an ONS pincer ligand with divalent iron, cobalt, copper and zinc are described. The ligand is synthesized by condensation of dihydroxybenzaldehyde with thiosemicarbazide. The reaction of the ligand with metal ions in 1:2 (M:L) stoichiometric in identical conditions resulted in two octahedral pincer type complexes with iron and cobalt in which two ligands extend a perpendicular shape-retaining the ligand’s linearity, and one trigonal bipyramidal pincer complex with zinc. For copper, the ligand preferred a bidentate coordination mode forming a square planar geometry. The structure of the copper complex can be viewed as a molecular hammock. Quantum mechanical studies at DFT level were undertaken to confirm the geometry, spectroscopic and electronic properties of all the complexes. The ability of the compounds to possess biological activity is tested against various pathogenic bacterial strains. The results show that the copper complex displays higher antimicrobial activities as compared to the ligand and other complexes. A remarkable change in the electronic spectrum of the ligand in the presence of cobalt ion in highly aqueous medium demonstrates its use as a metal sensor among a wide range of biological important metal ions.

The synthesis of new 1,2,3-thiadiazole and 1,2,3-selenadiazole derivatives from triterpenoid ketones has been investigated via the corresponding semicarbazones. The intermediates 5, 8 have also been isolated, separated and their structures identified. The Hurd–Mori reaction and Lalezari method have been applied to synthesize a series of new substances 6 and 7. The regioselectivity of the functionalization mostly was centered at the C-3 position for the products 9 and 10. The structures of these compounds were confirmed by 2D-NMR spectroscopy.

An interesting series of six new zinc complexes of 2-benzoylpyridine-N-4-phenyl semicarbazone(HL1) and 2-acetylpyridine-N-4-phenyl semicarbazone(HL2) have been synthesised and physico chemically characterized using techniques like infra red and electronic spectroscopic measurements. Ligand can exist in keto or enol form or an equilibrium mixture of the two since it has an amide –NH-C=(O) function. However, the IR spectrum of HL1 and HL2 indicates that in the solid state it remains in keto form. The v(C=N) bands of semicarbazones are found to be shifted to lower frequencies by 30-40 cm−l in all complexes representing the coordination via the azomethine nitrogen. The coordination of this nitrogen is also supported by a shift in v(N—N) frequencies. A shift to lower frequency is due to the conjugation of p-orbital on the double bond with the d-orbital on the metal atom with the reduction of the force constant. In the IR spectra of the complexes, the bands at 420-435 cm−l assignable to v(Zn-Nazo) further confirms the coordination of the metal through azomethine Nitrogen. In the electronic spectra, the ligand HLI showed bands at 37410 cm−l and 32890 cm-l and the ligand HL2 showed bands at 37010 cm−l and 33900 cm−l attributable to the π→π* transitions of the azomethine group. A new band around 23900-25300 cm-l can be assigned to metal→O charge-transfer band. The appearance of metal→O charge-transfer band in the electronic spectra of Zn(II) complex is a strong evidence that the keto oxygen atoms of the ligands are coordinated to the Zn(II) ion. The MLCT maxima of the complexes show line broadening into the visible part of the spectra. The semicarbazones and their zinc(II) complexes show a π→ π* band in the range 37000-38100 cm−l and an n→ π* band in the range 31000-34000 cm−l involving transitions within the semicarbazone moiety. The spectra of the complexes have bands with reduction in intensity than those of the ligands.

Reaction of 5-(morpholinisulfonyl)isatin (1) with thiosemicarbazide derivative appended the corresponding thiosemicarbazone derivative 3 that further coordinated with copper and zinc acetate to afford copper and zinc complexes 4 and 5, respectively. The structure of the ligand and its two complexes Cu (II) and Zn (II) are confirmed using elemental analysis, molar conductance, spectra data (FT-IR, 1H NMR, 13C NMR, mass spectra), and thermogravimetric analysis (TGA). The ligand bounds to metal complex as neutral tridentate (ONS) donor with tetrahedral geometry structure. Additionally, the ligand forms two five-member rings with metals via carbonyl of isatin derivative, the nitrogen of azomethane (C=N), and sulpher of thiosemicarbazone. The antimicrobial activity was evaluated against two Gram-positive, two Gram-negative bacteria, and one fungal strain. Both complexes revealed antimicrobial activity against the tested strains. In addition, the result exhibited that the zinc complex 5 displayed higher activity than copper complex 4, where the zinc complex 5 showed an inhibition zone between (18 ± 0.20 - 23 ± 0.31) mm and activity index ranged between (84-100%) compared with Tetracycline. Moreover, the zinc complex 5 exhibited MIC (24.59- 98.42 µM) in comparison to Tetracycline (35.14- 140.62 µM). Finally, the in silico molecular docking study for thiosemicarbazone derivatives 3, 4, and 5 were carried out inside five active sites as an antibacterial targets. Among them, the ligand and its metal complexes showed the lower binding affinity and suggested that these derivatives 3, 4, and 5 may possibly be DHFR and topoisomerase IV inhibitors.