Novel Schiff base metal complexes: synthesis,characterization, DNA binding,DNA cleavage and molecular docking studies

A novel Schiff base, 3-(((1H-1,2,4-triazol-3-yl)imino)methyl)-4H-chromen-4-one (L) was synthesized and used as ligand for the synthesis of Co(II), Ni(II), Cu(II), Zn(II) and Pd(II) complexes. The structural characterization of the ligand and its metal complexes was determined by using various physicochemical and spectroscopic methods. The IR data show that the Schiff base ligand acts as a bidentate donor coordinating through the oxygen atom of the chromone and nitrogen atom of the imine group. Based on all spectral data, tetrahedral geometry has been proposed for all the metal complexes except Cu(II) and Pd(II) complexes. However, square-planar geometry has been proposed for Cu(II) and Pd(II) complexes. DNA binding interaction of the ligand and its metal complexes was investigated by using UV–visible absorption, fluorescence and molecular docking studies. The binding constants were in the order of 10⁴ M^?1 suggesting good binding affinity towards CT-DNA. The DNA cleavage activity of the synthesized compounds was investigated by using agarose gel electrophoresis. In vitro antimicrobial activity of the synthesized compounds were screened against two gram-positive bacteria (Bacillus subtilis, Staphylococcus aureu) and two gram-negative bacteria (Escherichia coli, Proteus vulgaris) and one fungi strain Candida albicans using disc diffusion method. Antioxidant activity was carried out by DPPH radical scavenging method. In vitro anti-proliferative activity of the ligand and its metal complexes was also carried on the HEK-293, HeLa, IMR-32 and MCF-7 cancer cell lines using MTT assay.     

Synthesis,characterization, thermal,antimicrobial and antioxidant studies of some transition metal dithiocarbamates

Metal dithiocarbamate complexes of Co(II) [1], Cu(II) [2], Mn(II) [3], Cr(III) [4], and Pd(II) [5] have been synthesized using sodium N-ethyl-N-phenyldithiocarbamate (NaL). The complexes were characterized by elemental analyses, FTIR and UV–vis spectroscopic techniques, magnetic moment, molar conductance and thermal analyses (TGA and DSC). The infrared spectra indicated the coordination of dithiocarbamate through the two sulphur atoms in a symmetrical bidentate fashion. The thermal behavior of these complexes showed that the hydrated complexes lost water molecules in the first step, followed by decomposition of the ligand molecules in the final steps. Mass loss considerations at these final decomposition steps indicate conversion of the complexes to sulphides. The antimicrobial potentials of the complexes were evaluated against some selected bacteria strains (Escherichia coli, Pseudomonas aureginosa, Salmonella typhi and Staphylococcus aureus) and fungi organisms (Aspergillus flavus and Fasiparium oxysporium). The compounds showed a broad spectrum of fungicidal and bactericidal activities which exceeds that of the control drugs at a 100 μg/mL concentration. The antioxidant properties of the ligand and its Cu(II) complex were evaluated in vitro using DPPH assay, and the complex was found to exhibit better radical scavenging ability than the free ligand.     

Macrocyclic [N<Subscript>5</Subscript>] transition metal complexes: synthesis,characterization and biological activities

Novel penta-azamacrocyclic 21-membered [N₅] ligand [L] and its transition metal complexes with Co(II), Ni(II), Cu(II), Ru(III) and Pd(II) have been isolated and characterized. The mode of bonding and overall geometry of the complexes have been inferred through IR, MS, UV–Vis, EPR, ¹H NMR spectral studies, molar conductivity, magnetic, thermal and microanalyses, On the basis of above studies, an octahedral geometry has been proposed for all complexes except Pd(II) chloride complex which adopt square planar geometry. The in vitro antitumor activity of the synthesized ligand and some selected complexes against human breast and human hepatocarcinoma cell lines (MCF-7) and (HePG2), respectively has been studied. The results show that the tested compounds are potent antitumor agents. Also the ligand and some selected complexes have been tested for their inhibitory effect on the growth of bacteria: Streptococcus pyogenes as Gram-positive bacteria and Escherichia coli as Gram-negative bacteria. The activity data show that most of the tested compounds exhibit remarkable antibacterial activity against these organisms.     

Supramolecular structure,spectroscopic, thermal studies and antimicrobial activities of Schiff base complexes

Metal(II) complexes of 4-(((2-hydroxynaphthalen-1-yl)methylene)amino)-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one (HL) were prepared, and their compositions and physicochemical properties were characterized on the basis of elemental analysis, with¹HNMR, UV–Vis, IR, mass spectroscopy and thermogravimetric analysis. All results confirm that the novel complexes have a 1:1 (M:HL) stoichiometric formulae [M(HL)Cl₂] (M = Cu(II)(1), Cd(II)(5)), [Cu(L)(O₂NO)(OH₂)₂](2), [Cu(HL)(OSO₃)(OH₂)₃]2H₂O(3), [Co(HL)Cl₂(OH₂)₂]3H₂O(4), and the ligand behaves as a neutral/monobasic bidentate/tridentate forming a five/six-membered chelating ring towards the metal ions, bonding through azomethine nitrogen, exocyclic carbonyl oxygen, and/or deprotonated phenolic oxygen atoms. The XRD studies show that both the ligand and Cu(II) complex (1) show polycrystalline with monoclinic crystal structure. The molar conductivities show that all the complexes are non-electrolytes. On the basis of electronic spectral data and magnetic susceptibility measurements, a suitable geometry has been proposed. The trend in g values (g _ll > g _⊥ > 2.0023) suggest that the unpaired electron on copper has a \(d_{{x^{2} - y^{2} }}\) character, and the complex (1) has a square planar, while complexes (2) and (3) have a tetragonal distorted octahedral geometry. The molecular and electronic structures of the ligand (HL) and its complexes (1–5) have been discussed. Molecular docking was used to predict the binding between HL ligand and the receptors of the crystal structure of Escherichia coli (E. coli) (3t88) and the crystal structure of Staphylococcus aureus (S. aureus) (3q8u). The activation thermodynamic parameters, such as activation energy (E _a), enthalpy (ΔH), entropy (ΔS), and Gibbs free energy change of the decomposition (ΔG) are calculated using Coats–Redfern and Horowitz–Metzger methods. The ligand and its metal complexes (1–5) showed antimicrobial activity against bacterial species such as Gram positive bacteria (Bacillus cereus and S. aureus), Gram negative bacteria (E. coli and Klebsiella pneumoniae) and fungi (Aspergillus niger and Alternaria alternata); the complexes exhibited higher activity than the ligand.     

Spectroscopic and thermal characterization of biologically and anticancer active novel Schiff base metal complexes

The novel Schiff base ligand 2,2′-((1Z,1′Z)-(1,3-phenylenebis(azanylylidene))-bis(phenylmethanylylidene))dibenzoic acid (H₂L) was obtained by the condensation of m-phenylenediamine with o-benzoylbenzoic acid. The molecular and electronic structure of Schiff base ligand (H₂L) was optimized theoretically, and the quantum chemical parameters are calculated. Molecular docking was used to predict the binding between Schiff base ligand (H₂L) and the receptors of breast cancer mutant 3hb5-oxidoreductase, crystal structure E. coli (3t88) and crystal structure of S. aureus (3q8u). The newly synthesized Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), and Cd(II) complexes were characterized by elemental microanalysis, molar conductance, spectroscopic techniques (IR, ¹H NMR, ESI-mass, ESR, UV–Vis), magnetic susceptibility, thermal (TG/DTG) and powder X-ray diffraction data to explicate their structures. The data showed that the complexes had composition of MH₂L type. The IR results confirmed the bidentate binding of the ligand involving two azomethine nitrogens. ¹H NMR spectral data of the ligand (H₂L) and its Zn(II) and Cd(II) complexes agreed well with the proposed structures. On the basis of electronic spectra and the magnetic measurements, octahedral geometry of the complexes was proposed. Thermogravimetric data (TG and DTG) were also studied. The kinetic and thermodynamic parameters for thermal decomposition of the complexes were calculated using the Coats–Redfern and Horowitz–Metzger methods. In order to appraise the effect of antimicrobial activity of metal ions upon chelation, the newly synthesized ligand and its metal complexes were screened against a number of bacteria organisms as Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Neisseria gonorrhoeae and against one fungus, Candida albicans, to assess their inhibiting potential by using the disc diffusion method. The results showed that in some cases the antimicrobial activity of complexes was more biologically active than the Schiff base ligand. Anticancer activity of the ligand and its metal complexes were evaluated in human cancer (MCF-7 cells viability). It was found that [Cd(H₂L)(H₂O)₂Cl₂]2H₂O complex showed lowest IC₅₀ than the others, and hence was the more active. The activity index was calculated.     

Synthesis,crystal structures,and antibacterial activity of copper(II) and cobalt(III) complexes derived from 2-[(2-dimethylaminoethylimino)methyl]-4-methylphenol

A new tetranuclear copper(II) complex (I) and a new mononuclear cobalt(III) complex (II) have been synthesized from the Schiff base compound 2-[(2-dimethylaminoethylimino)methyl]-4-methylphenol. The complexes have been characterized by physico-chemical and spectroscopic methods, as well as single crystal X-ray determination (CIF files CCDC nos. 1447778 (I) and 1447779 (II)). The Cu atoms in complex I are in square pyramidal coordination, and the Co atom in complex II is in octahedral coordination. Crystal structures of the complex are stabilized by hydrogen bonds and π···π interactions. The complexes and the Schiff base compound were assayed for antibacterial activities against three Gram-positive bacterial strains (B. subtilis, S. aureus, and St. faecalis) and three Gram-negative bacterial strains (E. coli, P. aeruginosa, and E. cloacae) by MTT method. As a result, the complexes showed effective antimicrobial activity against the microorganisms tested.     

Novel repaglinide complexes with manganese(II), iron(III), copper(II) and zinc(II): Spectroscopic,DFT characterization and electrochemical behaviour

Novel transition metal complexes with the repaglinide ligand [2-ethoxy-4-[N-[1-(2piperidinophenyl)-3-methyl-1-1butyl] aminocarbonylmethyl]benzoic acid] (HL) are prepared from chloride salts of manganese(II), iron(III), copper(II), and zinc(II) ions in water-alcoholic media. The mononuclear and non-electrolyte [M(L)₂(H₂O)₂]?nH₂O (M = Mn²⁺, n = 2, M = Cu²⁺, n = 5 and M = Zn²⁺, n = 1) and [M(L)₂(H₂O)(OH)]?H₂O (M = Fe³⁺) complexes are obtained with the metal:ligand ratio of 1:2 and the L-deprotonated form of repaglinide. They are characterized using the elemental and molar conductance. The infrared, ¹H and ¹³C NMR spectra show the coordination mode of the metal ions to the repaglinide ligand. Magnetic susceptibility measurements and electronic spectra confirm the octahedral geometry around the metal center. The experimental values of FT-IR, ¹H, NMR, and electronic spectra are compared with theoretical data obtained by the density functional theory (DFT) using the B3LYP method with the LANL2DZ basis set. Analytical and spectral results suggest that the HL ligand is coordinated to the metal ions via two oxygen atoms of the ethoxy and carboxyl groups. The structural parameters of the optimized geometries of the ligand and the studied complexes are evaluated by theoretical calculations. The order of complexation energies for the obtained structures is as follows:

$$Fe(III) complex < Cu(II) complex < Zn(II) complex < Mn(II) complex.$$

The redox behavior of repaglinide and metal complexes are studied by cyclic voltammetry revealing irreversible redox processes. The presence of repaglinide in the complexes shifts the reduction potentials of the metal ions towards more negative values.

     

Synthesis,characterization, spectroscopic and catalytic oxidation studies of Fe(III), Ni(II), Co(III), V(IV) and U(VI) Schiff base complexes with N,O donor ligands derived from 2,3-diaminopyridine

Fifteen new complexes of transition metals were designed using three Schiff base ligands and aldol condensation of 2,3-diaminopyridine with 5-R-2-hydroxybenzaldehyde (R = F, Cl, Br) in the 1:2 molar ratio. The tetradentate ligands N,N′-bis(5-R-2-hydroxybenzaldehyde) pyridine were acquired with the common formula H₂[(5-R-sal)₂py] and characterized by IR, UV–Vis spectra, ¹H-NMR and elemental analysis. These ligands produce 1:1 complexes M[(5-R-sal)₂py] with Fe(III), Ni(II), Co(III), V(IV) and U(VI) metal ions. The electronic property and nature of complexes were identified by IR, UV–Vis spectra, elemental analysis, X-ray crystallography and cyclic voltammetric methods. The catalytic activity of complexes for epoxidation of styrene with UHP as primary oxidant at minimal temperature (10 °C) has been planned. The spectral data of the ligands and their complexes are deliberate in connection with the structural changes which happen due to complex preparation. The electrochemical outcome has good conformability with what suggested for electronic interaction among metal center and ligand by the UV–Vis and IR measurements.     

Synthesis,crystal structure,and fluorescence properties of a two-dimensional copper(II) complex with Schiff base

A new Schiff base ligand C₁₉H₁₃NO₅(H₂L) was synthesized using 2-aminoterephthalic acid and 2-hydroxy-1-naphthaldehyde. A complex of this ligand [Cu(C₁₉H₁₁NO₅)(C₂H₆O)] _n was synthesized and characterized by IR, UV, fluorescence spectroscopy and X-ray diffraction single-crystal analysis. The crystal crystallizes in the monoclinic system, space group Pbca with a = 8.7745(18), b = 18.613(4), c = 24.644(5) Å, V = 4024.9(14) ų, Z = 8, F(000) = 1816, S = 1.009, ρ _calcd = 1.462 g cm^?3, μ = 1.122 mm^?1, the final R = 0.0477 and wR = 0.1594 for 4609 observed reflections (I > 2σ(I)). The Cu(II) is five-coordinated by one N atom and two O atoms from the Schiff base ligand and two carboxylate O atoms from another two ligands to form a distorted square-pyramidal geometry. Each ligand serves as a bridging ligand to link Cu²⁺ ions, leading to a two-dimensional coordination polymer. The fluorescence properties of the ligand and complex were also studied. The ligand shows strong fluorescence, and the fluorescence intensity is weakened after the Cu(II) complex formed.     

X-ray photoelectron spectra and structure of polynuclear nickel complexes

Mono- and binuclear nickel complexes of different stoichiometry have been studied by X-ray photoelectron spectroscopy (XPS). The Ni2p, Ni3p, and N1s X-ray photoelectron spectra have been examined, and the role of a ligand in their formation has been determined. As distinct from a low-spin Ni(II) complex, the Ni2p spectra of high-spin Ni(II) compounds show strong satellite lines. For high-spin Ni(II) complexes, which have unpaired 3d electrons, the Ni2p _1/2-Ni2p _3/2 spin-orbit splitting is larger than that for a low-spin Ni(II) compound. The presence or absence of the satellite structure has made it possible to classify these complexes with regard to their magnetic properties. The difference between the Ni2p _3/2 and N1s binding energies has made it possible to estimate the covalence of the metal-ligand bond. The XPS results are consistent with X-ray crystallography data.     

Synthesis,characterization and crystal structures of new Zinc(II) and Nickel(II) complexes containing morpholine moiety and their antibacterial studies

The ligand 1,2-dimorpholinoethane (DME) was used to prepare Zn(II) and Ni(II) complexes of the general formulation MLX₂ (L = DME, X = Cl or NO₃). Zinc(II) complex exhibits spectral properties indicative of a distorted tetrahedral geometry, with DME coordinating through two nitrogen atoms and two chlorides completing the tetrahedron. This is in contrast to the six-coordinated, distorted octahedral geometry exhibited by nickel(II) complex of DME when NO₃ was used as counter ions. The X-ray diffraction confirms the structures of two complexes and shows that the ligand coordinates through two nitrogen atoms while the two ether linkages are not involved in complexation, which would have been the case if the morpholine rings were in the boat form. The ligand and related complexes have antibacterial activity against the five Gram-positive bacteria: Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC 6538, Bacillus cereus NRRL-B-3711, Enterococcus faecalis ATCC 29212 and Streptococcus pyogenes and also against the three Gram-negative bacteria: Escherichia coli ATCC 11230, Pseudomonas aeruginosa ATCC 15442 and Klebsiella pneumonia ATCC 70063. The results showed that in some cases the antibacterial activity of the complexes exceeded the one of sulfisoxazole used as a standard.     

DNA interactions and anticancer screening of copper(II) complexes of <Emphasis Type="Italic">N</Emphasis>-(methylpyridin-2-yl)-amidino-<Emphasis Type="Italic">O</Emphasis>-methylurea

Cu(II) complexes of the tridentate ligand N-(methylpyridin-2-yl)-amidino-O-methylurea (L), namely [Cu(L)Cl₂] and [Cu(L)ClO₄]ClO₄, have been investigated for interactions with DNA by spectroscopic methods and viscosity measurements. Both complexes bind to DNA through non-intercalative interactions. [Cu(L)Cl₂] (K _b = 2.81 × 10⁵ M^?1) shows similar DNA-binding potential to [Cu(L)ClO₄]ClO₄ (K _b = 1.57 × 10⁵ M^?1). Investigation of the chemical nuclease properties toward plasmid pBR322 DNA by gel electrophoresis and atomic force microscopy (AFM) suggests that both complexes are able to cleave the supercoiled form (Form I) to the nicked (Form II) and linear forms (Form III) through an oxidative pathway. The possible reactive oxygen species have been investigated by the use of scavengers, indicating that hydroxyl radicals may be involved in the DNA cleavage mechanism. Both of these complexes show similar activities against selected human cancer cell lines.     

Synthesis,characterization, DFT modeling and biological studies of new Co(II), Ni(II) and Cu(II) 4,6-bis(4-chlorophenyl)-2-amino-1,2-dihydropyridine-3-carbinitrile complexes

Three new metal complexes of 4,6-bis(4-chlorophenyl)-2-amino-1,2-dihydropyridine-3-carbinitrile (L) with Co(II), Ni(II) and Cu(II) were synthesized and characterized with physicochemical and spectroscopic techniques. The data suggest that (L) acts as a bidentate ligand bound to the divalent metal ions through amino N and carbinitrile N atoms having [M(L)₂(H₂O)₂]²⁺ formula (M = metal ions). The theoretical parameters, model structures, charges and molecular orbitals of all possible complexes have been determined using density functional theory. The energy gap of free ligand is ?E = 0.12565 eV, and this value is greater than energy gap of complexes, which indicates that the complexes are more reactive than free ligand. Also, ?E of Co(II) complex is lower than other complexes, which indicates that Co(II) complex is more reactive than Ni(II) and Cu(II) complexes. The antibacterial and antifungal activities of the ligand, metal salts and its complexes were tested against some microorganisms (bacteria and fungi). The complexes showed increased antibacterial and antifungal profile in comparison with the free ligand.     

Macrocyclic Cu(II) and Pd(II) complexes with new 16-membered tetradentate [N<Subscript>4</Subscript>] ligand: synthesis,characterization, 3D molecular modeling and in vitro anticancer and antimicrobial activities

New Cu(II) and Pd(II) complexes of tetradentate macrocyclic nitrogen ligand i.e. (10E,13E)-11,13-dimethyl-4H-dibenzo[g,n]naphtho[1,8-bc][1,5,9,13]tetraazacyclohexa-decine 5,19(12H,20H)-dione have been synthesized. The compounds have been characterized by elemental analyses, spectral (IR, UV–Vis, ¹H NMR, MS and ESR), 3D molecular modeling, molar conductivity, magnetic as well as thermal analysis measurements. On the basis of above studies, tetragonally distorted octahedral or square planar geometry has been proposed for the complexes. Also, the in vitro antitumor activity of the synthesized ligand and most complexes against human breast and human hepatocarcinoma cell lines (MCF-7 and HepG2, respectively) has been studied. Furthermore, the current compounds have been screened for their possible antimicrobial activity against Staphylococcus aureus as Gram-positive bacteria, Escherichia coli as Gram-negative bacteria Aspergillus flavus and Candida albicans as antifungal agents.     

S,S-Complexes of Copper(I) Halides with 1,2-Bis(3,5-dimethyloxazol-4-ylmethylsulfanyl)ethane as New Catalysts for Phenylacetylene Aminomethylation

New metal–heterocycle S,S-complexes based on Cu(I) binary halides and a polydentate ligand, 1,2- bis(3,5-dimethyloxazol-4-ylmethylsulfanyl)ethane have been prepared. The obtained complexes have demonstrated high catalytic activity in aminomethylation of phenylacetylene with N,N,N',N'-tetramethylmethanediamine, bis(oxazolidin-3-yl)methane, or benzaldehyde–piperidine system.     

Syntheses and Crystal Structures of Quinidinum-Zinc(II)-Trichloride and Quinidinum Iron(III) Tetrachloride Hydrogen Chloride Hydrate

A mononuclear coordination complex, quinidinum-zinc(II)-trichloride (I), and a multi-component ionic complex, quinidinum iron(III) tetrachloride hydrogen chloride hydrate (II), have been synthesized and characterized by elemental analyses, IR spectra, and single crystal X-ray diffraction (CIF files nos. 1497628 (I) and 1497629 (II)). The weak hydrogen-bonding interactions exist in both complexes I and II. Both complexes crystallize in the chiral space groups with the absolute configuration. Complex I crystallizes in the orthorhombic space group P2₁2₁2₁ with a = 7.6651(6), b = 11.4923(9), c = 24.653(2) Å, and Z = 4. Complex II crystallizes in the monoclinic space group P2₁ with a = 6.6425(15), b = 18.660(4), c = 10.958(3) Å, β = 104.973(3), and Z = 2.     

Complexes of cobalt(II) halides with 2-(1<Emphasis Type="Italic">H</Emphasis>-pyrazol-1-yl)-4(3<Emphasis Type="Italic">H</Emphasis>)-pyrimidinone

The electronic structures of complexes of cobalt(II) halides with 2-(1H-pyrazol-1-yl)-4(3H)-pyrimidinone have been studied by X-ray photoelectron spectroscopy. The Co2p _3/2 lines of cobalt atoms, N1s lines of nitrogen atoms, and O1s lines of oxygen atoms in the X-ray photoelectron spectra have been analyzed. Based on these data for the free and coordinated ligands, the atoms of the ligand coordinated to the central metal atom are determined. The coordinated organic compound serves as an electron-donating ligand. The results obtained are consistent with IR and UV-Vis spectroscopic data.     

Synthesis,crystal structures,and antimicrobial activity of a pair of isostructural dinuclear copper(II) complexes derived from 4-nitro-2-[(2-diethylaminoethylimino)methyl]phenol

A pair of isostructural azido- or thiocyanato-bridged centrosymmetric dinuclear copper(II) complexes, [Cu₂L₂(μ_1,3-N₃)₂] (1) and [Cu₂L₂(μ_1,3-NCS)₂] (2), derived from the Schiff base ligand 4-nitro-2-[(2-diethylaminoethylimino)methyl]phenol (HL), have been synthesized and characterized by elemental analysis, IR spectra and single crystal X-ray diffraction. Each Cu atom in the complexes is five-coordinate in a square pyramidal geometry by one O and two N atoms of one Schiff base ligand, and by two terminal donor atoms from two bridging azide or thiocyanate ligands. Both the azide and thiocyanate ligands adopt end-to-end bridging mode in the complexes. The distance between the two copper atoms is 5.205(2) Å for (1) and 5.515(2) Å for (2). The antimicrobial activity of the complexes has been tested.     

Chemical and Electrochemical Synthesis,Structure, and Properties of Metal Chelates of Tridentate N,S-Containing Azomethinazo Ligands

Novel Cu(II), Co(II), Ni(II), and Zn(II) complexes of 5-methyl-2-phenyl-4-[(4-phenylazo)anilinemethylylidene]- 2,4-dihydro-3H-pyrazole-3-thione and 5-methyl-4-[4-methyl-2-(4-methylphenylazo)anilinemethylylidene]- 2-phenyl-2,4-dihydro-3H-pyrazole-3-thione, i.e. ligands containing the phenylazo group in the ortho and para positions of the aniline fragment, were synthesized by the chemical and electrochemical methods. The complexes and ligands were characterized by IR, ¹H NMR, X-ray absorption spectroscopy and magnetochemistry. The azo group of the ligands is not involved in coordination to the metal.     

Synthesis,DFT calculations and characterisation of new mixed Pt(II) complexes with 3-thiolanespiro-5<Emphasis Type="Italic">′</Emphasis>-hydantoin and 4-thio-1<Emphasis Type="Italic">H</Emphasis>-tetrahydropyranspiro-5<Emphasis Type="Italic">′</Emphasis>-hydantoin

Cisplatin is an anticancer drug widely used in the treatment of a wide range of solid tumours (head and neck, lung, bladder etc.), testicular and ovarian cancers. Because of its severe toxicity profile and spontaneous development of drug resistance in tumours, a number of Pt(II) complexes have been synthesised and tested for anti-tumour activity. Some of the investigations have focused on using ligands bearing donor atoms other than N (e.g., S, P, O). Two new mixed Pt(II) complexes of the general formula cis-[Pt(NH₃)LCl₂] where L is 3-thiolanespiro-5′-hydantoin and 4-thio-1H-tetrahydropyranspiro-5′-hydantom were synthesised. The complexes were studied by elemental analysis, melting points, IR and ¹H NMR spectra. The hybrid DFT calculations were used for optimisation of the structure geometries of the ligands III, IV and their Pt(II) complexes V and VI. The structural parameters so calculated, such as bond lengths and angles, are in good agreement with the experimental data for similar hydantoins and their platinum complexes. The results showed that the geometries of complexes V and VI are plane square and the bounding of ligands III and IV with platinum ions is effected by the sulphur atom from the cyclic ring. The complexes thus obtained were chemically examined in comparison with previously synthesised and published complexes of the general formula cis-[PtL₂Cl₂] (VII and VIII) with the same ligands. The new compounds V and VI, as well as the previously investigated complexes (VII and VIII), were analysed for cytotoxicity in vitro on SKW-3 and HL-60 human tumour cell lines. The results showed that all the complexes exerted concentration-dependent anti-proliferative activity.