Synthesis, structure and antitumor activity of a water-soluble platinum complex, (1R,3R,4R,5R)-(-)-quinato(1R,2R-cyclohexanediamine)platinum (II).

The reaction of dihydroxo(1R,2R-cyclohexanediamine)platinum(II) with (-)-quinic acid gave a water soluble complex, (-)-quinato(1R,2R-cyclohexanediamine)platinum(II). The crystal structure of the complex was determined by X-ray analysis. The data indicate a chelation of the alpha-hydroxycarboxylic acid part of quinic acid to platinum(II). The complex shows moderate antitumor activity against murine leukemia L1210 at high doses (T/C x 100 = 179% at a dose of 200 mg/kg).     

Synthesis and antitumor activities of alkyl-1,4-butanediamine Pt(II) complexes having seven-membered ring structure

Novel alkyl-1,4-butanediamine Pt(II) complexes having a seven-membered ring structure were synthesized and characterized by fast atom bombardment mass and infrared spectra and elemental analysis. Their antitumor activities in vivo toward lymphoid leukemia L1210 and Lewis lung carcinoma LL were studied in the case where the leaving group was either dichloride or cyclobutane-1,1-dicarboxylate. 1,4-Butanediamine Pt(II) complexes (seven-membered ring) showed higher antitumor activities than those of ethylenediamine Pt(II) (five-membered ring) and 1,3-propanediamine Pt(II) (six-membered ring) complexes toward L1210 for both leaving groups. Alkyl-1,4-butanediamine Pt(II) complexes showed high antitumor activities toward L1210, except for 1,1-dimethyl-1,4-butanediamine Pt(II) complexes. In particular, 2,2-dimethyl-1,4-butanediamine and 2,3-dimethyl-1,4-butanediamine Pt(II) complexes exhibited excellent antitumor activities with T/C% values higher than 300. None of the dichloro Pt(II) complexes showed antitumor activities toward LL, but the cyclobutane-1,1-dicarboxylato Pt(II) complexes, which were moderately active toward L1210 with T/C% values around 200, also showed high antitumor activities toward LL with T/C% values of more than 200. Alkyl-1,4-butanediamine Pt(II) complexes with a seven-membered ring structure were found to be stable and to have antitumor activities in vivo.     

Syntheses, molecular structures, electrochemical behavior, theoretical study, and antitumor activities of organotin(IV) complexes containing 1-(4-chlorophenyl)-1-cyclopentanecarboxylato ligands

The organotin(IV) compounds [Me(2)Sn(L)(2)] (1), [Et(2)Sn(L)(2)] (2), [(n)Bu(2)Sn(L)(2)] (3), [(n)Oct(2)Sn(L)(2)] (4), [Ph(2)Sn(L)(2)] (5), and [PhOSnL](6) (6) have been synthesized from the reactions of 1-(4-chlorophenyl)-1-cyclopentanecarboxylic acid (HL) with the corresponding diorganotin(IV) oxide or dichloride. They were characterized by IR and multinuclear NMR spectroscopies, elemental analysis, cyclic voltammetry, and, for 2, 3, 4 and 6, single crystal X-ray diffraction analysis. While 1-5 are mononuclear diorganotin(IV) compounds, the X-ray diffraction of 6 discloses a hexameric drumlike structure with a prismatic Sn(6)O(6) core. All these complexes undergo irreversible reductions and were screened for their in vitro antitumor activities toward HL-60, BGC-823, Bel-7402, and KB human cancer cell lines. Within the mononuclear compounds, the most active ones (3, 5) are easiest to reduce (least cathodic reduction potentials), while the least active ones (1, 4) are the most difficult to reduce. Structural rearrangements (i.e., Sn-O bond cleavages and trans-to-cis isomerization) induced by reduction, which eventually can favor the bioactivity, are disclosed by theoretical/electrochemical studies.     

Synthesis,crystal structure,and in vitro antitumor activities of copper(II) complexes containing tetradentate pyridine-based ligands

Several new Cu(II) complexes of Schiff bases obtained by condensation of 2-[N-(α-picolyl)-amino]-benzophenone with different chiral amino acids were synthesized and characterized by physico-chemical and spectroscopic methods. The crystal structure of one of the complexes was determined using single crystal X-ray diffraction. The ligands were coordinated to the metal atom in a tetradentate manner with ONNN donor sets using the carboxyl oxygen, azomethine nitrogen, CON⁻, and pyridine nitrogen. The cytotoxicities of the complexes were evaluated against human cancer cells. The substituents on the aromatic rings strongly influenced the cytotoxicities of the complexes. The complex with bromine substituents on the pyridine rings showed the highest cytotoxicity. The antitumor activities against tumor cell lines were assayed in vitro, and the complexes were found to be highly effective, with six of the nine complexes having inhibition ratios better than that of 5-Fluorouracil. This behavior is indicative of a high ability to circumvent the cellular drug resistance mechanisms.     

Syntheses,characterizations, and antimicrobial activities of binuclear ruthenium(III) complexes containing 2-substituted benzimidazole derivatives

Binuclear ruthenium(III) complexes [RuX₃L]₂?·?nH₂O (X?=?Cl, L?=?L¹, L², L³; n?=?1, L⁴ and L⁵, X?=?Br; L?=?L³), [RuX₃L_1.5]₂?·?nH₂O (X?=?Br, L?=?L¹; n?=?0, L⁴; n?=?6 and L⁵; n?=?10), and [RuX₃L₂]₂ (X?=?Br, L?=?L²) have been isolated by treatment of hydrated RuX₃ (X?=?Cl/Br) in acetone with 2-(2′-aminophenylbenzimidazole) (L¹), 2-(3′-aminophenylbenzimidazole) (L²), 2-[(3′-N-salicylidinephenyl)benzimidazole] (L³), 2-(3′-pyridylbenzimidazole) (L⁴), and 2-(4′-pyridylbenzimidazole) (L⁵) in acetone. The complexes were characterized by elemental analysis, conductivity and magnetic susceptibility measurements, IR, electronic, EPR, and mass spectral studies. The complexes were dimeric; based on analytical and spectral studies, an octahedral geometry was proposed for the complexes. The synthesized complexes were screened against Gram-positive and Gram-negative bacteria and fungi.     

The crystal structure and absolute configuration of the antitumor platinum complex trans(OH)-Pt(OH)2(malonato)(1R,2R-cyclohexanediamine).

The absolute configuration of the anti-tumor complex trans(OH)-Pt(OH)2(malonato)(1R,2R-cyclohexanediamine) was determined by X-ray anomalous scattering technique. The final unit cell was monoclinic, space group P2(1) with a = 9.142 A, b = 7.788 A, c = 11.946 A, beta = 96.48 degrees, Z = 2. The crystal structure was determined by direct method and difference Fourier synthesis, and refined to R = 0.025 and Rw = 0.033 based on 2768 independent reflections. The platinum atom has roughly octahedral coordination. The cyclohexane ring has the expected chair configuration, with two amino groups in equatorial positions while the malonato ligand, in contrast, shows a boat conformation for six membered Pt O-C-C-C-O ring.     

Syntheses and catalytic activities of Pd(II) dicarbene and hetero-dicarbene complexes

A series of palladium(II) complexes (1-6) bearing cis-chelating homo-dicarbene ligands with varying alkyl bridges (C1-C3) and N-heterocyclic backbones (imidazole and benzimidazole) have been synthesized by reaction of Pd(OAc)₂ with the respective diazolium bromides (A·2HBr - F·2HBr) in DMSO. A comparative catalytic study employing aryl chlorides in the Mizoroki-Heck reaction revealed the superiority of methylene- and propylene-bridged dibenzimidazolin-2-ylidenes over their imidazole-derived analogues. Based on these results, two new propylene-bridged hetero-dicarbene complexes (7 and 8) were designed containing a mixed benzimidazole/imidazole-derived NHC-donor set. Notably, both complexes outperformed their homo-dicarbene analogues, which may be due to the electronic asymmetry induced by hetero-dicarbene ligands. The molecular structures of complex 6 and 8 are also presented.     

Syntheses,crystal structures,and antibacterial activities of manganese(III), nickel(II), and copper(II) complexes containing a tetradentate Schiff base

Three new mononuclear Schiff-base complexes, namely [Mn(L)Cl] (1), [Ni(L)] (2), and [Cu(L)] (3), where L?=?anion of [N,N′-bis(2-hydroxybenzophenylidene)]propane-1,2-diamine, have been synthesized by reacting equimolar amounts of the respective metal chloride and the tetradentate Schiff base, H₂L, in methanol. The complexes have been characterized by microanalytical, spectroscopic, single-crystal X-ray diffraction, and other physicochemical studies. Structural studies reveal that 1 adopts a distorted square-pyramidal geometry whereas 2 and 3 are isotypic with distorted square-planar geometries. The antibacterial activities of 1–3 along with their Schiff base have been tested against some Gram(+) and Gram(?) bacteria.     

Molecular structures of antitumor active Pd(II) and Pt(II) complexes of N,N-donor benzimidazole methyl ester

[MLCl₂]?·?zH₂O?·?C₂H₅OH (L?=?2-[(1H-benzimidazol-2-ylmethyl)-amino]-benzoic acid methyl ester; M?=?Pd, z?=?2; M?=?Pt, z?=?0) complexes were synthesized as potential antitumor compounds and their structures were elucidated by elemental analysis and spectroscopic data. Theoretical molecular structures were investigated by the DFT/B3LYP method using the LANL2DZ basis set. The calculated molecular parameters, bond distances, and angles, revealed a square-planar geometry around the metal through pyridine-type nitrogen (N_py) of benzimidazole and the secondary amino group (NH_sec). The lone pair interaction LP(2)O48 of ethanol with anti-bonding σ*(C(16)–H(29)) is an evidence for charge transfer from ethanol to platinum. The electronic movement and assignment of electronic spectra were carried out by TD-DFT calculations. The ligand in comparison to its metal complexes was screened for antibacterial activity and cytotoxicity.     

Syntheses and antitumor and anti-aids activities of polymers containing pyrimidine derivative

The new monomer, 5'-O-methacryloyl-3'-azido-3'-deoxy-thymidine (MAZT), was synthesized from methacryloyl chloride (MAC) and 3'-azido-3'-deoxythymidine (AZT). Poly(MAZT), poly(MAZT-co-AA) and terpoly(MAZT-FUR-MAH) were synthesized by radical polymerizations. The average molecular weights of synthesized polymers were in the range of 8,800 ∼23,000 depending on polymers. The in vivo antitumor activities of polymers at 800mg/kg were increased in the following order: terpoly(MAZT-FUR-MAH) >x poly(MAZT-co-AA) > poly(MAZT) > AZT > 5-FU. The in vitro anti-HIV activities of synthesized polymers were less effective than those of AZT and D4T. But the cytotoxicities of the polymers on the MT-4 cell line were found to be much less toxic than AZT.     

Syntheses,crystal structures,electrochemical studies,and antioxidant activities of zinc(II) and copper(II) complexes with bis(2-benzimidazolyl) aniline derivatives

Two ligands, bis(benzimidazol-2-ylmethyl) aniline (bba) and bis(N-methyl-benzimidazol-2-ylmethyl) aniline (Mebba), and their transition metal complexes [Zn(bba)(Br)₂]·2DMF (1) and [Cu(Mebba)(Br)₂]·2DMF (2) have been synthesized and characterized by elemental analyses, molar conductivities, UV–vis spectra, IR spectra, NMR spectroscopy, and X-ray crystallography. The structure around Zn(II) can be described as distorted tetrahedral. Complex 2 can be described as distorted trigonal bipyramidal. Cyclic voltammograms of 2 indicate a quasireversible Cu²⁺/Cu⁺ couple. Additionally, the antioxidant activities of the free ligands and their complexes were determined by the superoxide and hydroxyl radical scavenging methods in vitro. Complexes 1 and 2 possess potent hydroxyl radical scavenging activity and better than standard antioxidants such as vitamin C and mannitol. Complex 2 possesses excellent superoxide radical activity.     

Synthesis,characterization, and antitumor activities of two copper(II) complexes with pyrazole derivatives

Two mononuclear copper(II) complexes with pyrazole derivatives, 1,1′-(anthracen-9-ylmethylene)bis(1H-pyrazole) (L¹ ) and 9-(4-(di(1H-pyrazol-1-yl)methyl)phenyl)-9H-carbazole (L² ), of formulae [CuL¹(CH₃CN)₂](ClO₄)₂ (1) and [CuL²(CH₃CN)₂](ClO₄)₂ (2) were prepared. Both complexes were confirmed by IR, MS, ¹H NMR, and elemental analyses. Complex 1 was also characterized by X-ray crystallography, confirming that copper(II) is coordinated by four nitrogen atoms from two L¹ and two oxygen atoms from two perchlorates. Furthermore, all ligands and complexes were tested in vitro for their antitumor activities using mouse melanoma cell line B16-F10, HepG2 human hepatoma cell line, and A549 human lung adenocarcinoma cell line. Both complexes displayed potent cytotoxicity and are promising substrates for further investigations.     

The nature of cis amine Pd(II) and antitumor cis amine Pt(II) complexes in aqueous solutions

Upon addition of base the complex enPd(OH₂)₂²⁺ rapidly dimerizes to form a binuclear dihydroxo bridged dimer with no significant mononuclear hydroxo complexes at 10 mM concentration. The corresponding Pt(II) complex titrates two equivs base with pK_a 5.8 and 7.6 to give a dihydroxo complex which is stable indefinitely. Addition of only one equiv of base to yield near neutral solutions slowly produces the Pt(II) dihydroxo bridged dimer. The hydroxo groups of dienPtOH⁺, dienPdOH⁺ and enPt(OH⁻)₂ are effective nucleophiles for ester hydrolysis and their reactivities are in accord with a suggested dependence on basicity. The antitumor complexes of cis dichloro Pt(II) amines are converted to aquo and hydroxo complexes of Pt(II) amines. Due to the low ambient chloride ion concentration within a cell, aquo complexes are present in significant amounts and are most likely to be the reactive species. The reactivity of cis Pt(II) amine antitumor complexes is reduced by Cl⁻, OH⁻ and dihydroxy bridged dimer substituents, the formation of which is time dependent.     

Syntheses,characterization, and antimicrobial properties of nickel(II) dithiocarbamate complexes containing NiS4 and NiS2PN moieties

Three Ni(II) dithiocarbamate complexes, [Ni(buphdtc)₂] (1), [Ni(buphdtc)(PPh₃)(NCS)] (2) and [Ni(buphdtc)(PPh₃)(NC)] (3) (where bu = butyl and ph = phenyl), were synthesized and characterized by elemental analysis, UVvis, and FTIR spectroscopies. Complexes 1 and 2 were further characterized by single-crystal X-ray structural analysis. The single-crystal X-ray structural analysis indicates a slightly distorted square planar geometry. In 2 and 3, the influences of the auxiliary ligands (PPh₃, NCS, and NC) on their steric and electronic properties were observed. Thermal studies of the complexes showed decomposition starting at 250–300 °C, leading to formation of nickel sulfide phases around 400 °C. The complexes were screened against some bacteria strains, Staphylococcus aureus, Streptococcus pneumoniae, Bacillus subtilis, Escherichia coli, Klebsiella oxytoca and Pseudomonas aeruginosa, and two fungi species, Aspergillus niger and Fusarium oxysporum. The complexes showed moderate-to-strong antimicrobial potentials, with [Ni(buphdtc)₂] (1) displaying the best antimicrobial activity. Fluconazole and streptomycin were used as reference drugs for antifungal and antibacterial assays, respectively.     

Synthesis,physico-chemical characterization and bioevaluation of Ni(II), Pd(II), and Pt(II) complexes with 1-(o-tolyl)biguanide: Antimicrobial and antitumor studies

New complexes of type [M(tbg)₂]Cl₂ [tbg = 1-(o-tolyl)biguanide; M = Ni(II), Pd(II), and Pt(II)] were synthesized and characterized to develop new biologically active compounds. The features of the complexes were assigned from microanalytical and thermal data. The NMR, FT-IR, and UV-Vis spectra were established by comparison with HtbgCl. All complexes exhibit a square-planar geometry resulting from the chelating behavior of tbg. The HtbgCl and [Ni(tbg)₂]Cl₂ complexes were fully characterized by single-crystal X-ray diffraction. The HtbgCl species crystallize in the monoclinic C2/c spatial group, while the Ni(II) complex adopts an orthorhombic Pna2₁ spatial group. The structure is stabilized by a complex hydrogen bonds network. The in vitro antimicrobial assays revealed improved antimicrobial activity for complexes in comparison with the ligand against both planktonic and biofilm embedded microbial cells. The most efficient compound, showing the largest spectrum of antimicrobial activity, including Gram-positive and Gram-negative bacteria, as well as fungal strains, in both planktonic and biofilm growth states was the Pd(II) complex, followed by the Pt(II) complex. The Pt(II) compound exhibited the most significant antiproliferative activity on the human cervical cancer SiHa cell line, inducing a cell cycle arrest in the G2/M phase.