Green approach to synthesize novel thiosemicarbazide complexes, characterization; DNA-methyl green assay and in-silico studies against DNA polymerase.

A thiosemicarbazide derivative as (E)-4-ethyl-1-(1-(naphthalen-1-yl) ethylidene) thiosemicarbazide (HAN) was synthesized then characterized to prepare [Co(HAN)Cl2·(H2O)2], [Ni(HAN)Cl2·(H2O)2]. H2O, and [Cd(HAN)Cl2] complexes. According to spectral and analytical data we could confirm the neutral bidentate mode of bonding via (C]S) and (C]N) groups to form 1:1 M ratio within the three complexes. The octahedral geometry was suggested for Co(II) and Ni(II) complexes according to electronic transitions assigned to 4T1g → 4T1g(P)(ʋ2) and 4T1g → 4A2g(F)(ʋ3) and 3A2g → 3T1g(P,υ3) and 3A2g → 3T1g(F,υ2), respectively. The values of nephelauetic ratio (ß) in the ligand field parameters detect the ionic nature of new M-L bonds. The molecular ion peaks appeared in the mass spectra of two selected complexes confirming their molecular formulae. The conductometric study was performed for Cd(II) ion solution during variable additions of HAN to calculate association and formation constant of Cd(II)-HAN complex. DFT/B3LYP method was used to optimize the structures of the compounds and confirm the binding mode of the ligand. The distribution of C(5) = N(17) and C(13) = S(19) groups asserts their priority in coordination. Hirshfeld crystal properties were obtained via normalized contact distance (dnorm) and shape index in which the nitrogen atoms act as the best contact points in crystal packing. The biological screening was carried out against microbial strains as well as methyl green/DNA test. In vitro, the superiority of the ligand was clearly recorded in its biological effectiveness. In silico methods were implemented to confirm the activity of the ligand and to recognize the interaction features. The bioavailability, pharmacokinetics and drug-likeness were evaluated via Swiss-link. The data detect the ability of the ligand to penetrate barrier of brain (BBB) but not absorbed in gastrointestinal tract. Pharmit link and molecular docking were utilized to investigate the interaction of HAN with 1bna, 425d and 2k4l proteins. The best intercalation with protein pockets was observed with 2k4l protein, and searching the MolPort library detects a drug analog of MolPort-002-894-701. Finally, the results suggest the biological efficiency of the ligand, which may be asserted by specialists through intensive in-vivo studies.

Spectral, Molecular Modeling, and Biological Activity Studies on New Schiff's Base of Acenaphthaquinone Transition Metal Complexes.

The newly synthesized Schiff's base derivative, N-allyl-2-(2-oxoacenaphthylen-1(2H)-ylidene)hydrazine-1-carbothioamide, has been characterized by different spectral techniques. Its reaction with Co(II), Ni(II), and Zn(II) acetate led to the formation of 1 : 1 (M:L) complexes. The IR and NMR spectral data revealed keto-thione form for the free ligand. On chelation with Co(II) and Ni(II), it behaved as mononegative and neutral tridentate via O, N1, and S donors, respectively, while it showed neutral bidentate mode via O and N1 atoms with Zn(II). The electronic spectra indicated that all the isolated complexes have an octahedral structure. The thermal gravimetric analyses confirmed the suggested formula and the presence of coordinated water molecules. The XRD pattern of the metal complexes showed that both Co(II) and Ni(II) have amorphous nature, while Zn(II) complex has monoclinic crystallinity with an average size of 9.10 nm. DFT modeling of the ligand and complexes supported the proposed structures. The calculated HOMO-LUMO energy gap, ΔEH-L, of the ligand complexes was 1.96-2.49 eV range where HAAT < Zn(II) < Ni(II) < Co(II). The antioxidant activity investigation showed that the ligand and Zn(II) complex have high activity than other complexes, 88.5 and 88.6%, respectively. Accordingly, the antitumor activity of isolated compounds was examined against the hepatocellular carcinoma cell line (HepG2), where both HAAT and Zn(II) complex exhibited very strong activity, IC50 6.45 ± 0.25 and 6.39 ± 0.18 µM, respectively.

Synthesis of Novel VO(II)-Perimidine Complexes: Spectral, Computational, and Antitumor Studies.

A series of perimidine derivatives (L1-5) were prepared and characterized by IR, 1H·NMR, mass spectroscopy, UV-Vis, XRD, thermal, and SEM analysis. Five VO(II) complexes were synthesized and investigated by most previous tools besides the theoretical usage. A neutral tetradentate mode of bonding is the general approach for all binding ligands towards bi-vanadyl atoms. A square-pyramidal is the configuration proposed for all complexes. XRD analysis introduces the nanocrystalline nature of the ligand while the amorphous appearance of its metal ion complexes. The rocky shape is the observable surface morphology from SEM images. Thermal analysis verifies the presence of water of crystallization with all coordination spheres. The optimization process was accomplished using the Gaussian 09 software by different methods. The most stable configurations were extracted and displayed. Essential parameters were computed based on frontier energy gaps with all compounds. QSAR parameters were also obtained to give another side of view about the biological approach with the priority of the L3 ligand. Applying AutoDockTools 4.2 program over all perimidine derivatives introduces efficiency against 4c3p protein of breast cancer. Antitumor activity was screened for all compounds by a comparative view over breast, colon, and liver carcinoma cell lines. IC50 values represent promising efficiency of the L4-VO(II) complex against breast, colon, and liver carcinoma cell lines. The binding efficiency of ligands towards CT-DNA was tested. Binding constant (K b) values are in agreement with the electron-drawing character of the p-substituent which offers high K b values. Also, variable Hammett's relations were drawn.

Spectral studies on a series of metal ion complexes derived from pyrimidine nucleus, TEM, biological and γ-irradiation effect.

A series of thiouracil complexes was prepared, all the prepared compounds are investigated by all possible tools. The ligand coordinates towards two central atoms as a neutral hexadentate mode. The octahedral structure was proposed with Ni(II), Pt(IV) and UO2(II) complexes. Square-pyramidal and square planar with VO(II) and Pd(II) complexes, respectively. VO(II) complex was irradiated by using Gamma radiation to through a light on the probability of geometry changes with the effect of radiation. The parameters calculated from ESR spectra before and after γ-irradiation reflect the rigidity of the complex towards the effect. Such may discuss the unaffected biological behavior before and after irradiation. XRD patterns were carried out to emphasis on the nature of the particles and the purity of products. The ligand, Pt(IV) and Pd(II) are found in nanometer range. TEM is a sensitive tool used to justify on the microstructure and surface morphology. All the investigated compounds are in nanorange. TG curves reflect a lower thermal stability of all investigated complexes due to the presence of water of crystallization. Finally, a toxic effect was observed with all investigated complexes towards Gram positive bacterium as well as a resistant behavior was observed with Gram negative bacteria.

Spectral and Eukaryotic DNA degradation studies for Ni(II), Pd(II), Pt(IV), Cu(II) and UO2(2+) complexes derived from thiouracil derivative.

A derivative of thiouracil ligand was prepared. Ni(II), Pd(II), Pt(IV), Cu(II) and UO2(2+) complexes were prepared. The elemental and different spectral tools were used for their characterization. A binegative tetradentate mode is the general coordination behavior of the ligand towards all metal ions used. The structural geometries were varied from square-planer (Pt, Pd(II)), square-pyramidal (Cu(II)) and octahedral (UO2(2+)). The geometry optimization implementing the hyperChem reveals that the Cu(II) complex is the most stable one. The thermogravimetric analysis supports the presence of solvent molecules attached with most complexes. The biological investigation was studied on different microorganisms as gram-positive, gram-negative and fungia. The Ni(II) complex shows the most toxic activity towards most organisms used. The degradation effect of DNA was studied by the use of investigated compounds and reveal that the Ni(II) and Pd(II) complexes are the most effective on the DNA degradation.

In-vitro antibacterial, antifungal activity of some transition metal complexes of thiosemicarbazone Schiff base (HL) derived from N4-(7'-chloroquinolin-4'-ylamino) thiosemicarbazide.

The synthetic, spectroscopic, and biological studies of Cu(II), Ni(II), Zn(II), Co(II), Mn(II), Fe(III) and Cr(III) complexes of N(4)-(7'-chloroquinolin-4'-ylamino)-N(1)-(2-hydroxy-benzylidene)thiosemicarbazone (HL) obtained by the reaction of N(4)-(7'-chloroquinolin-4'-ylamino)thiosemicarbazide with 2-hydroxybenzaldehyde. The structures of the complexes were determined on the basis of the elemental analyses, spectroscopic data (IR, electronic, (1)H and (13)C NMR and Mass spectra) along with magnetic susceptibility measurements, molar conductivity and thermogravimetric analyses. Electrical conductance measurement revealed the non-electrolytic nature of the complexes. The resulting colored products are mononuclear in nature. On the basis of the above studies, only one ligand was suggested to be coordinated to each metal atom by thione sulfur, azomethine nitrogen and phenolic oxygen to form mononuclear complexes in which the thiosemicarbazone behaves as a monobasic tridendate ligand. The ligand and its metal complexes were tested against Gram + ve bacteria (Staphylococcus aureus), Gram - ve bacteria (Escherichia coli), fungi (Candida albicans) and (Fusarium solani). The tested compounds exhibited significant activity.

Transition metal complexes of isonicotinic acid (2-hydroxybenzylidene)hydrazide.

A new series of transition metal complexes of Schiff base isonicotinic acid (2-hydroxybenzylidene)hydrazide, HL, have been synthesized. The Schiff base reacted with Cu(II), Ni(II), Co(II), Mn(II), Fe(III) and UO2(II) ions as monobasic tridentate ligand to yield mononuclear complexes of 1:2 (metal:ligand) except that of Cu(II) which form complex of 1:1 (metal:ligand). The ligand and its metal complexes were characterized by elemental analyses, IR, UV-vis, mass and 1H NMR spectra, as well as magnetic moment, conductance measurements, and thermal analyses. All complexes have octahedral configurations except Cu(II) complex which has an extra square planar geometry distorted towards tetrahedral. While, the UO2(II) complex has its favour hepta-coordination. The ligand and its metal complexes were tested against one strain Gram +ve bacteria (Staphylococcus aureus), Gram -ve bacteria (Escherichia coli), and Fungi (Candida albicans). The tested compounds exhibited higher antibacterial activities.