A novel copper(II) complex identified as a potent drug against colorectal and breast cancer cells and as a poison inhibitor for human topoisomerase IIα.

A novel complex, [Cu(acetylethTSC)Cl]Cl•0.25C2H5OH 1 (where acetylethTSC = (E)-N-ethyl-2-[1-(thiazol-2-yl)ethylidene]hydrazinecarbothioamide), was shown to have anti-proliferative activity against various colon and aggressive breast cancer cell lines. In vitro studies showed that complex 1 acted as a poison inhibitor of human topoisomerase IIα, which may account for the observed anti-cancer effects.

Hexa-µ-acetato-1:2κ(4) O,O';1:2κ(2) O:O;2:3κ(4) O,O';2:3κ(2) O:O-bis-(4,4'-dimethyl-2,2'-bi-pyridine)-1κ(2) N,N';3κ(2) N,N'-2-calcium-1,3-dizinc.

In the centrosymmetric trinuclear Zn(II)⋯Ca(II)⋯Zn(II) title complex, [CaZn2(CH3COO)6(C12H12N2)2], the Ca(II) ion lies on an inversion centre and is octa-hedrally coordinated by six acetate O atoms. The Zn(II) ion is coordinated by two N atoms from a bidentate di-methyl-bipyridine ligand and three O atoms from acetate ligands bridging to the Ca(II) ion, leading to a distorted square-pyramidal coordination sphere. The Zn⋯Ca distance is 3.4668 (5) Å.

Chlorido{4-ethyl-1-[1-(pyrazin-2-yl)ethyl-idene]thio-semicabazidato-κS}bis-(triphenyl-phosphane-κP)silver(I).

The title compound, [Ag(C9H13N5S)Cl(C18H15P)2], crystallizes with four independent mol-ecules in the asymmetric unit, in each of which the Ag atom is in a distorted tetra-hedral coordination, defined by the chloride ligand, the S atom of the neutral ligand and two P atoms derived from the triphenyl phosphine ligands. The thio-semicarbazone acts as a monodentate ligand through its thione S atom. An intra-molecular N-H⋯Cl hydrogen bond occurs in two of the independent mol-ecules. In the crystal, the mol-ecules are assembled through N-H⋯Cl hydrogen bonds, forming chains along [101].

Iodido{4-phenyl-1-[1-(1,3-thia-zol-2-yl-κN)ethyl-idene]thio-semicarbazidato-κ(2) N',S}{4-phenyl-1-[1-(1,3-thia-zol-2-yl)ethyl-idene]thio-semicarbazide-κS}cadmium(II).

In the title complex, [Cd(C12H11N4S2)I(C12H12N4S2)], the Cd(II) ion is penta-coordinated by two thio-semicarbazone ligands (one neutral and the other anionic) and one iodide ion in a distorted square pyramidal (τ = 0.35) geometry. The central ion is coordinated by the thia-zole N atom, the thio-ureido N and the S atom of the deprotonated thio-semicarbazone ligand. The other ligand is linked with the central ion through the C=S group. The deprotonated ligand intra-molecularly hydrogen bonds to the thia-zole ring N atom, while the ligand forms an inter-molecular hydrogen bond to the thiol-ate S atom of the second ligand. The deprotonation of the tridentate ligand and its coordination to the Cd(II) ion via the S atom strikingly affects the C-S bond lengths. The C-S bond lengths in the neutral and deprotonated ligands in the metal complex are 1.709 (3) and 1.748 (2) Å, respectively, whereas it is 1.671 (3) Šin the free ligand. In the metal complex, the Cd-S distances are 2.6449 (6) and 2.5510 (6) Å. The Cd-I bond length is 2.7860 (2) Å.

N (1)-(Thio-phen-2-ylmeth-yl)-N (3),N (3)-bis-[3-(thio-phen-2-yl-methyl-ammonio)-prop-yl]propane-1,3-di-ammonium hexa-fluorido-silicate methanol tris-olvate.

In the title compound, C24H40N4S3 (4+)·2SiF6 (2-)·3CH3OH, the central tertiary amine function is protonated and is connected to three thio-phen-2-yl-methyl-amino-n-propyl groups, forming the arms of a T-shaped cation that has two pockets. Each arm contains one protonated secondary amine function, and each pocket is occupied by one SiF6 (2-) anion bonded via two N-H⋯F inter-actions with the protonated amine group on the middle arm, while two methanol solvent mol-ecules are N-H⋯O hydrogen-bonded with the other secondary protonated amine groups on the side arms. Weak O-H⋯O and O-H⋯F hydrogen bonds between the solvent mol-ecules and between the solvent mol-ecules and the anions, respectively, are also observed. All three thio-phene groups in the arms are disordered over two sets of sites, with occupancy ratios of 0.828 (3):0.172 (3), 0.910 (2):0.090 (2) and 0.890 (3):0.110 (3).

Synthesis, characterization, and preliminary in vitro studies of vanadium(IV) complexes with a Schiff base and thiosemicarbazones as mixed-ligands.

[VO(Sal-L-tryp)(H2O)] 1 (where sal-L-tryp = N-salicylidene-L-tryptophanate) was used as a precursor to produce the novel complexes, [VO(Sal-L-tryp)(MeATSC)].1.5C2H5OH 2 (where MeATSC = 9-Anthraldehyde-N(4)-methylthiosemicarbazone), [VO(Sal-L-tryp)(N-Ethhymethohcarbthio)].H2O 3 (where N-Ethhymethohcarbthio = (E)-N-ethyl-2-(4-hydroxy-3-methoxybenzylidene)hydrazinecarbothioamide), and [VO(Sal-L-tryp)(acetylethTSC)].C2H5OH 4 (where acetylethTSC = (E)-N-ethyl-2-(1-(thiazol-2-yl)ethylidene)hydrazinecarbothioamide), by reaction with the respective thiosemicarbazone. The chemical and structural properties of these ligands and complexes were characterised by elemental analysis, ESI MS, FT-IR, UV-visible, ESR, 1H and 13C NMR spectroscopy, and X-ray crystallography. DMSO and DMSO-d6 solutions of compounds 1-4 were oxidised in air to produce vanadium(V) species which were verified by ESI MS and 51V NMR spectroscopy. Anti-cancer properties of compounds 2-4 were examined with three colon cancer cell lines, HTC-116, Caco-2, and HT-29, and also with non-cancerous colonic myofibroblasts, CCD18-Co. Compounds 2-3 exhibited less inhibitory effects in the CCD-18Co cells, indicating a possible cytotoxic selectivity towards colon cancer cells. In general, those compounds which exhibited anti-proliferative activity on cancer cells, but did not affect non-cancerous cells, may have a potential in chemotherapy.

Iodido{4-phenyl-1-[1-(1,3-thia-zol-2-yl-κN)ethyl-idene]thio-semicarbazidato-κN',S}{4-phenyl-1-[1-(1,3-thia-zol-2-yl)ethyl-idene]thio-semicarbazide-κS}mercury(II).

In the title compound, [Hg(C(12)H(11)N(4)S(2))I(C(12)H(12)N(4)S(2))], the Hg atom is in a distorted square-pyramidal coordination, defined by the iodide ligand, by the S atom of the neutral ligand in the apical position, and by the N atom of the thia-zole ring, the thio-ureido N and the S atom of the deprotonated ligand. The deprotonated ligand intra-molecularly hydrogen bonds to the thia-zole ring N atom, while the deprotonated ligand forms an inter-molecular hydrogen bond to the thiol-ate S atom. The deprotonation of the tridentate ligand and its coordination to Hg via the S atom strikingly affects the C-S bond lengths. In the free ligand, the C-S bond distance is 1.685 (7) Å, whereas it is 1.749 (7) Šin the deprotonated ligand. Similarly, the Hg-S bond distance is slightly longer to the neutral ligand [2.6682 (18) Å] than to the deprotonated ligand [2.5202 (19) Å]. The Hg-I distance is 2.7505 (8) Å.

Chloridodiphen-yl{[1-(1,3-thia-zol-2-yl-κN)ethyl-idene]-4-phenyl-thio-semicarbazidato-κN,S}tin(IV) methanol monosolvate.

The title compound, [Sn(C(6)H(5))(2)(C(12)H(11)N(4)S(2))Cl]·CH(4)O, is formed during the reaction between 2-acetyl-thia-zole 4-phenyl-thio-semicarbazone (Hacthptsc) and diphenyl-tin(IV) dichloride in methanol. In the crystal structure, the Sn atom exhibits an octa-hedral geometry with the [N(2)S] anionic tridentate thio-semicarbazone ligand having chloride trans to the central N and the two phenyl groups trans to each other. The Sn-Cl distance is 2.5929 (6), Sn-S is 2.4896 (6) and Sn-N to the central N is 2.3220 (16) Å. The MeOH mol-ecules link the Sn complexes into one-dimensional chains via N-H⋯O and O-H⋯Cl hydrogen bonds.

5-Nitro-1-nonyl-1H-benzimidazol-2(3H)-one.

In the title mol-ecule, C(16)H(23)N(3)O(3), the dihedral angle between the benzimidazole and nitro group planes is 5.34 (9)° and the dihedral angle between the benzimidazole and aliphatic chain mean planes is 73.23 (5)°. The C-C-C-C torsion angles (about 176°) of the nonyl group indicate an all-anti-periplanar conformation. In the crystal, adjacent mol-ecules are linked by pairs of N-H⋯O hydrogen bonds into inversion dimers. These mol-ecules are further connected through C-H⋯O inter-actions, building tapes parallel to (22).

1,3-Bis[2-(2-oxo-1,3-oxazolidin-3-yl)eth-yl]-1H-benzimidazol-2(3H)-one.

The mol-ecular structure of the title compound, C(17)H(20)N(4)O(5), contains a central fused-ring system, comprised of six- and five-membered rings. This unit is linked by C(2) chains to two 2-oxo-1,3-oxazolidine five-membered rings. The central fused-ring system is essentially planar, with a maximum deviation of 0.008 (1) Šfrom the mean plane. Both oxazolidine five-membered rings are also nearly planar, with maximum deviations of 0.090 (1) and 0.141 (1) Å.

3-[(1-Benzyl-1H-1,2,3-triazol-5-yl)meth-yl]-6-bromo-2-phenyl-3H-imidazo[4,5-b]pyridine.

There are two crystallographically independent mol-ecules in the asymmetric unit of the title compound, C(22)H(17)BrN(6). The dihedral angles between the imidazo[4,5-b]pyridine mean plane and the phenyl rings are 20.4 (2) and 24.0 (2)° in the two mol-ecules. The orientation of triazoles compared to the imidazo[4,5-b]pyridine system is almost the same in both mol-ecules, with dihedral angles of 64.2 (2) and 65.1 (2)°. However, the main difference between the two mol-ecules lies in the arrangement of the phenyl groups compared to imidazo[4,5-b]pyridine in each mol-ecule. Indeed, in the first mol-ecule the dihedral angle between the plane of the phenyl ring and that of the imidazo[4,5-b]pyridine system is 67.7 (2)°, while in the second mol-ecule the plane of the phenyl ring is almost perpendicular to that of the imidazo[4,5-b]pyridine system with a dihedral angle of 86.0 (2)°.

{4-Phenyl-1-[1-(1,3-thia-zol-2-yl)ethyl-idene]-thio-semicarbazidato}{4-phenyl-1-[1-(1,3-thia-zol-2-yl)ethylidene]-thio-semi-carbazide}nickel(II) chloride mono-hydrate.

In the title compound, [Ni(C(12)H(11)N(4)S(2))(C(12)H(12)N(4)S(2))]Cl·H(2)O, the Ni(II) ion is chelated by two 2-acetyl-thia-zole-3-phenyl-thio-semicarbazone ligands, forming a distorted octa-hedral complex. The metal ion is coordinated via the thia-zole nitro-gen, imine nitro-gen and thione sulfur atoms from each thio-semicarbazone ligand, and two coordinating units lie almost perpendicular to each other give dihedral angle = 81.89 (1)°]. One thio-semicarbazone unit is found to bind a chloride anion through two hydrogen bonds, while the other is linked with the disordered crystal water molecule. Two mol-ecules are connected to each other through an inter-molecular N-H⋯S inter-action, forming a centrosymmetric dimer. Dimers are linked into sheets by π-π stacking of two phenyl rings [shortest C⋯C distance = 4.041 (3) Å].

Chlorido(1-cyclo-pentyl-idene-4-ethyl-thio-semicarbazidato-κN,S)diphenyl-tin(IV).

The Sn atom in the title compound, [Sn(C(6)H(5))(2)(C(8)H(14)N(3)S)Cl], is penta-coordinated with a trigonal-bipyramidal coordination geometry. The 1-cyclo-pentyl-idene-4-ethyl-thio-semicarbazidate (cpetsc) ligand coordinates through the S atom and the N atom bonds to the cyclo-pentyl group, forming a five-membered ring with the Sn center. The chloride ligand and the coordinated N atom are in axial positions. In the crystal structure, inter-molecular N-H⋯Cl hydrogen bonds form chains along [101].

Iodidotris(triphenyl-phosphine)copper(I) acetonitrile solvate.

The title compound, [CuI(C(18)H(15)P)(3)]·C(2)H(3)N, was obtained from the reaction of triphenyl-phosphine and copper(I) iodide in acetonitrile. The monomeric form of the complex has slightly distorted coordination of Cu by the I atom and three P atoms. The crystal structure is stabilized by C-H⋯π inter-actions between phenyl H atoms and phenyl rings. In addition, the complex mol-ecules exhibit C-H⋯N hydrogen bonds between phenyl H atoms and acetonitrile N atoms. The crystal used was an inversion twin, with nearly equal component populations of 0.522 (8) and 0.478 (8).

Rhodamine 6G hexa-chlorido-stannate(IV) acetonitrile disolvate.

In the title compound, bis({6-ethylamino-10-[2-(methoxycarbonyl)phenyl]-2,7-dimethylxanthen-3-ylidene}ethanaminium) hexachloridotin(IV) acetonitrile disolvate, (C(27)H(29)N(2)O(3))(2)[SnCl(6)]·2C(2)H(3)N, the octa-hedral SnCl(6) (2-) anion lies on an inversion center. The xanthene ring system is essentially planar, with an average deviation of 0.020 Å, and the substituent benzene ring forms a dihedral angle of 85.89 (2)° with it. The Sn-Cl distances are in the range 2.4237 (3)-2.4454 (3) Å. There are N-H⋯Cl hydrogen bonds between SnCl(6) (2-) ions and rhodamine 6G cations as well as π-π stacking inter-actions between rhodamine 6G cations (inter-planar distance of 3.827 Å).

Synthesis and structure-activity correlation studies of metal complexes of alpha-N-heterocyclic carboxaldehyde thiosemicarbazones in Shewanella oneidensis.

This investigation involved the synthesis of metal complexes to test the hypothesis that structural changesand metal coordination in pyridine thiosemicarbazones affect cell growth and cell proliferation in vitro. Thiosemicarbazones are well known to possess antitumor, antiviral, antibacterial, antimalarial, and other activities. Extensive research has been carried out on aliphatic, aromatic, heterocyclic and other types of thiosemicarbazones and their metal complexes. Due to the pronounced reactivity exhibited by metal complexes of heterocyclic thiosemicarbazones, synthesis and structural characterization of di-2-pyridylketone 4N-phenyl thiosemicarbazone and diphenyl tin (Sn) and platinum (Pt) complexes were undertaken. Shewanella oneidensis MR-1, a metal ion-reducing bacterium, was used as a model organism to explore the biological activity under aerobic conditions. A comparision of the cytotoxic potential of selected ligand and metal-complex thiosemicarbazones on cell growth in wild type MR-1 and mutant DSP-010 Shewanella oneidensis strains at various concentrations (0, 5, 10, 15, 20 or 25 ppm) was performed. The wild type (MR-1) grown in the presence of increasing concentrations of Sn- thiosemicarbazone complexes was comparatively more sensitive (mean cell number = 4.8 X 10(8) +/- 4.3 X 10(7) SD) than the DSP-010, a spontaneous rifampicillin derivative of the parent strain (mean cell number = 5.6 x 10(8) +/- 6.4 X 10(7) SD) under comparable aerobic conditions (p = 0.0004). No differences were observed in the sensitivity of the wild and mutant types when exposed to various concentrations of diphenyl Pt- thiosemicarbazone complex (p = 0.425) or the thiosemicarbazone ligand (p = 0.313). Growth of MR-1 in the presence of diphenyl Sn-thiosemicarbazone was significantly different among treatment groups (p = 0.012). MR-1 cell numbers were significantly higher at 5ppm than at 10 to 20ppm (p = 0.05). The mean number of DSP-010 variant strain cells also differed among diphenyl Sn- thiosemicarbazone complex treated groups (p = 0.051). In general, there was an increasing trend in the number of cells from about 5.0 X 10(8) cells (methanol control group) to about 6.0 X 10(8) cells (25ppm). The number of cells in methanol control group was significantly lower than cell numbers at 20ppm and 25ppm (p = 0.05), and numbers at 5ppm treatment were lower than at 20 and 25ppm (p = 0.05). Furthermore, a marginally significant difference in the number of MR-1 cells was observed among diphenyl Pt- thiosemicarbazone complex treatment groups (p = 0.077), and an increasing trend in the number of cells was noted from approximately 5.0 X 10(8) cells (methanol control group) to approximately 5.8 X 10(8) cells (20ppm). In contrast, the DSP-010 variant strain showed no significant differences in cell numbers when treated with various concentrations of diphenyl Pt- thiosemicarbazone complex (p = 0.251). Differences in response to Sn- metal complex between MR-1 and DSP-010 growing cultures indicate that biological activity to thiosemicarbazone metal complexes may be strain specific.

Research training and biomedical education.

In an effort to increase the number of well trained minority healthcare professionals and basic science researchers, Jackson State University, (JSU, a historically black institution) in partnership with Hinds Community College (HCC, a 2-year college) and consultant biomedical researchers/healthcare professionals at the University of Mississippi Medical Center established a Bridges to the Baccalaureate Degree Program (BBDP). The purpose of the BBDP was to enhance HCC students transfer rates to 4 year institutions and to motivate trainees to seek Baccalaureate and advanced degrees in the biomedical and health sciences areas. The program utilized faculty and administrators at each institution in the planning and implementation of all programmatic aspects, including student selection, advisement procedures and program activities. HCC students (280) were recruited, 94.5 % of whom were African American, and trained in research laboratory methodologies, responsible conduct of research concepts, literature survey mechanisms, and scientific writing techniques during the academic year. Students engaged in specific individualized research projects during the summer and presented their research findings at local scientific seminars and professional meetings e.g., Mississippi Academy of Sciences, ABRCMS, FASEB, and the Endocrine Society. Sixty-five percent of students eligible to transfer actually transferred to Jackson State University and 8 other colleges and universities. Approximately 70% of the transfer students obtained Baccalaureate degrees and many received or are enrolled in masters and doctorate degree programs. HCC science faculty also received additional research training experiences and in 6 cases, initiated or completed terminal degrees in the sciences. In conclusion, it is clear that exposure to research training in the biomedical sciences can enhance community college students transfer rates and potential to seek advanced degrees.

Formation of an Amine-Water Cyclic Pentamer: A New Type of Water Cluster in a Polyazacryptand.

Structural analysis of an adduct of a thiophene-based cryptand with tosylic acid shows the formation of a hybrid amine-water cyclic pentamer composed of four water molecules and one protonated amine in the charged hydrophobic cavity. The bulky tosylate groups remain outside the cavity, making the ligand favorable for hosting water molecules. Ab initio calculations based on density functional theory (DFT) confirm that the hybrid amine-water pentamer is stabilized inside the hydrophobic cavity of the cryptand.

The 1:1 adduct of hexamethylenetetramine (HMT) with racemic trans-1,2-cyclohexanedicarboxylic acid (CDA).

Hexamethylenetetramine and rac-trans-1,2-cyclohexanedicarboxylic acid crystallize in a 1:1 ratio as a neutral molecular adduct, C6H12N4.C8H12O4. Two dicarboxylic acid molecules and two tetramine molecules form a hydrogen-bonded ring, in the shape of a rhombus, which lies on a crystallographic twofold axis bisecting the two diacid molecules. The O-H...N hydrogen bonds have lengths 2.6808 (19) and 2.6518 (19) A, and, in each ring, both acid molecules have the same handedness.

Cocrystallization of melaminium levulinate monohydrate.

Crystals of 2,4,6-triamino-1,3,5-triazin-1-ium levulinate (4-oxopentanoate) monohydrate, C(3)H(7)N(6)(+).C(5)H(7)O(3)(-).H(2)O, are formed via self-assembled hydrogen bonding by cocrystallization of melamine and levulinic acid. Two N-H.N hydrogen bonds and four N-H.O hydrogen bonds connect two melaminium entities such that each of two pairs of N-H.O bonds bridges two H atoms belonging to the amine groups of two different melaminium cations via the carbonyl O atom of one levulinate molecule.