Preparation of platinum(II) complexes with L-serine using KI. X-ray crystal structure, HPLC and 195Pt NMR spectra

The preparation of platinum(II) complexes containing L-serine using K(2)[PtCl(4)] and KI as raw materials was undertaken. The cis-trans isomer ratio of the complexes in the reaction mixture differed significantly depending on whether KI was present or absent in the reaction mixture. One of the two [Pt(L-ser-N,O)(2)] complexes (L-ser=L-serinate anion) prepared using KI crystallizes in the monoclinic space group P2(1)2(1)2(1) with unit cell dimensions a=8.710(2) A, b=9.773(3) A, c=11.355(3) A, Z=4. The crystal data revealed that this complex has a cis configuration. The other [Pt(L-ser-N,O)(2)] complex also crystallizes in the monoclinic space group P2(1)2(1)2(1) with unit cell dimensions a=7.0190(9) A, b=7.7445(6) A, c=20.946(2) A, Z=4. The crystal data revealed that this complex has a trans configuration. The 195Pt NMR chemical shifts of trans-[Pt(L-ser-N,O)(2)] and cis-[Pt(L-ser-N,O)(2)] complexes are -1632 and -1832 ppm, respectively. 195Pt NMR and HPLC measurements were conducted to monitor the reactions of the two [Pt(L-ser-N,O)(2)] complexes with HCl. Both 195Pt NMR and HPLC showed that the reactivities of cis- and trans-[Pt(L-ser-N,O)(2)] toward HCl are different: coordinated carboxyl oxygen atoms of trans-[Pt(L-ser-N,O)(2)] were detached faster than those for cis-[Pt(L-ser-N,O)(2)].     

Preparation of platinum(IV) complexes with dipeptide and diimine. X-ray crystal structure and 195Pt NMR spectra

We prepared platinum(IV) complexes containing dipeptide and diimine or diamine, the [PtCl(dipeptide-N,N,O)(diimine or diamine)]Cl complex, where -N,N,O means dipeptide coordinated as a tridentate chelate, dipeptide=glycylglycine (NH(2)CH(2)CON(-)CH(2)COO(-), digly, where two protons of dipeptide are detached when the dipeptide coordinates to metal ion as a tridentate chelate), glycyl-L-alanine (NH(2)CH(2)CON(-)CHCH(3)COO(-), gly-L-ala), L-alanylglycine (NH(2)CH CH(3)CON(-)CH(2)COO(-), L-alagly), or L-alanyl-L-alanine (NH(2)CHCH(3)CON(-)CHCH(3)COO(-), dil-ala), and diimine or diamine=bipyridine (bpy), ethylenediamine (en), N-methylethylenediamine (N-Me-en), or N,N'-dimethylethylenediamine (N,N'-diMe-en). In the complexes containing gly-L-ala or dil-ala, two separate peaks of the (195)Pt NMR spectra of the [PtCl(dipeptide-N,N,O)(diimine or diamine)]Cl complexes appeared in, but in the complexes containing digly or L-alagly, one peak which contained two overlapped signals appeared. One of the two complexes containing gly-L-ala and bpy, [PtCl(gly-L-ala-N,N,O)(bpy)]NO(3), crystallized and was analyzed. This complex has the monoclinic space group P2(1)2(1)2(1) with unit cell dimensions of a=9.7906(3)A, b=11.1847(2)A, c=16.6796(2)A, Z=4. The crystal data revealed that this [PtCl(gly-L-ala-N,N,O)(bpy)]NO(3) complex has the near- (Cl, CH(3)) configuration of two possible isomers. Based on elemental analysis, the other complex must have the near- (Cl, CH(3))-[PtCl(gly-L-ala-N,N,O)(bpy)]NO(3) configuration. The (195)Pt NMR chemical shifts of the near- (Cl, CH(3))-[PtCl(gly-L-ala-N,N,O)(bpy)]NO(3) complex and the far- (Cl, CH(3))-[PtCl(gly-L-ala-N,N,O)(bpy)]NO(3) complex are 0 ppm and -19 ppm, respectively (0 ppm for the Na(2)[PtCl(6)] signal). The additive property of the (195)Pt NMR chemical shift is discussed. The (195)Pt NMR chemical shifts of [PtCl(dipeptide-N,N,O)(bpy)]Cl appeared at a higher field when the H attached to the dipeptide carbon atom was replaced with a methyl group. On the other hand, the (195)Pt NMR chemicals shifts of [PtCl(dipeptide-N,N,O)(diamine)] appeared at a lower field when the H attached to the diamine nitrogen atom was replaced with a methyl group, in the order of [PtCl(digly-N,N,O)(en)]Cl, [PtCl(digly-N,N,O)(N-Me-en)]Cl, and [PtCl(digly-N,N,O)(N,N'-diMe-en)]Cl.     

Palladium(II) complexes of 2-benzoylpyridine-derived thiosemicarbazones: spectral characterization, structural studies and cytotoxic activity

Palladium(II) complexes of 2-benzoylpyridine thiosemicarbazone (H2Bz4DH) and its N4-methyl (H2Bz4M) and N4-phenyl (H2Bz4Ph) derivatives were obtained and fully characterized. [Pd(2Bz4DH)Cl] (1) crystallizes in the monoclinic space group P21/c with a=11.671(1), b=10.405(1), c=13.124(1), beta=115.60(1) degrees and Z=4; [Pd(2Bz4M)Cl] (2) in the monoclinic space group P21/c with a=9.695(1), b=15.044(1), c=10.718(1) A, beta=105.38(1) degrees and Z=4 and [Pd(2Bz4Ph)Cl] (3) in the triclinic space group P1 with a=9.389(1), b=13.629(1), c=15.218(1) A, alpha=70.25(1), beta=73.46(1), gamma=83.57(1) degrees and two independent molecules per asymmetric unit (Z=4). All complexes show a quite similar planar fourfold environment around palladium(II). A negatively charged organic molecule acts as a tridentate ligand and binds to the metal through the pyridine nitrogen, the imine nitrogen and the sulfur atom. A chloride ion occupies the fourth coordination site. The planar complexes stack nearly parallel to one another in the lattice conforming a layered crystal structure. The cytotoxic activity of the thiosemicarbazones and their metal complexes was tested against the MCF-7, TK-10 and UACC-62 human tumor cell lines. The ligands exhibit lower values of GI50 and LC50 than the complexes, H2Bz4Ph being the most active with GI50<0.003 microM; LC50=13.4 microM; GI50=9.3 microM, LC50=12.9 microM; GI50<0.003, LC50=13.8 microM in the MCF-7, TK-10 and UACC-62 cell lines, respectively. Among the complexes, [Pd(2Bz4Ph)Cl] (3) exhibited the lowest values of GI50 in the three studied cell lines.     

The preparation, characterisation, and DNA adduct profile of 2-amino-2-methyl-3-butanoneoximedichloroplatinum(II), a platinum(II) complex designed to bind to GpA sequences of DNA

The complex, 2-amino-2-methyl-3-butanoneoximedichloroplatinum(II), [Pt(ambo)Cl2], was chosen because of its potential to bind to GpA sequences of duplex DNA. Crystals of [Pt(ambo)Cl2] are monoclinic, space group, P2(1)/n, a = 6.799(4), b = 17.642(5), c = 8.193(2) A, beta = 102.10(3) degrees, Z = 4, R = 0.033 (1864 F). The binding of [Pt(ambo)Cl2] to salmon-sperm DNA was studied using enzymatic digestion and HPLC analysis. [Pt(ambo)Cl2] was found to form fewer GpG and ApG intrastrand adducts and more monofunctional adducts than [Pt(en)Cl2]. Binding to GpA sequences could not be established, but [Pt(ambo)Cl2] forms substantially more adducts with adenine than does [Pt(en)Cl2].     

Preparation, 195Pt NMR spectra and biological activity of platinum (IV) complexes with dipeptides

Three dipeptide complexes of the form K[Pt(IV) (dipep) Cl(OH)2] and four dipeptide complexes of the form K[Pt(IV)-(Hdipep)Cl2(OH)2] were newly prepared. The 195 Pt NMR peak of the K[Pt(IV) (dipep)Cl(OH)2] complexes appeared at about 1200 ppm and these chemical shifts were about 3150 ppm downfield compared with those of the K[Pt(II) (dipep) Cl] complexes. The chemical shifts of the K[Pt(IV) (Hdipep) Cl2 (OH)2] complexes were at about 900 ppm, i.e., about 3050 ppm downfield compared with those of the K[Pt(II) (Hdipep)Cl] complexes. The H[Pt(IV) (Hdigly) Cl2(OH)2] and K[Pt(IV) (Hdigly) Cl2(OH)2] complexes inhibited the growth of C. albicans at a more diluted concentration than cisplatin at 1 microgram/ml, but the platinum complexes only weakly inhibited the growth of these cells compared with the cisplatin-inhibited growth of Meth-A and Hep-2 cells at 10 micrograms/ml. These results suggested that the platinum complexes selectively inhibited the growth of fungal cells.     

Thiourea derivatives and their nickel(II) and platinum(II) complexes: antifungal activity

We have synthesized two thiourea derivatives of methyl anthranilate (1, 2) and their complexes with nickel (3) and platinum(II) (4). We have also prepared the complexes of nickel(II) with two benzoylthiourea derivatives (5, 6). The obtained compounds were characterized by elemental analysis, spectroscopic methods (FT-IR, UV-vis, NMR), mass spectrometry and thermal analysis. Compound 1, C(20)H(23)N(3)O(2)S, crystallizes in monoclinic space group P21/n, with Z=4, and unit cell parameters, a=8.8042(4) A, b=7.6608(3) A, c=28.834(2) A, alpha=gamma=90 degrees, beta=90.94(1) degrees. Compound 2, C(20)H(21)N(3)O(3)S, crystallizes in monoclinic space group P21/c, with Z=4, and unit cell parameters, a=7.7345(4) A, b=8.6715(4) A, c=29.113(2) A, alpha=gamma=90 degrees, beta=90.67(1) degrees. Compound 5, C(24)H(30)N(4)NiO(2)S(2), crystallizes in monoclinic space group P21/n, with Z=4, and unit cell parameters, a=10.4317(8) A, b=18.517(2) A, c=13.299(1) A, alpha=gamma=90 degrees, beta=104.53(1) degrees. Compound 6, C(25)H(28)Cl(2)N(4)NiO(4)S(2), crystallizes with a molecule of CH(2)Cl(2) in triclinic space group P-1, with Z=2, and unit cell parameters, a=10.362(1) A, b=11.849(2) A, c=12.536(2) A, alpha=90.04(2) degrees, beta=84.73(1) degrees, gamma=113.43(2) degrees. Compounds 1 and 2 show antifungal activity against the major pathogens responsible for important plant diseases (Botrytis cinerea, Colletotrichum fragariae, Fusarium oxysporum and Phoma betae). The antifungal activity is practically the same for morpholine and ethyl derivatives.     

Model complexes with naturally occurring ligands (salicylglycine and imidazol) and the biometals copper and cobalt

Two new complexes [Cu(Imz)(4)Cl(2)][Cu(Imz)(4)Cl] (2)(2-OH-Hip)(2) (1) and [Co(2-OH-Hip)(Imz)(3)].H(2)O (2) (with Imz=Imidazol and 2-OH-Hip=2-hydroxyhippuric acid) were prepared and characterized. The molecular structures and the solution and solid state behavior of the complexes were investigated. Complex 1 crystallizes in the monoclinic space group P2(1)/c with a=16.880(1), b=8.046(1), c=24.683(1) A, beta=107.88(1) degrees, and Z=2, while complex 2 crystallizes in the orthorhombic space group Pbca with a=11.712(2), b=15.741(4), c=22.254(4) A, and Z=8. The [Cu(Imz)(4)Cl(2)][Cu(Imz)(4)Cl](2)(2-OH-Hip)(2) solid consists in two distinct monomeric Cu(II) complexes: one of them is neutral octahedral [Cu(Imz)(4)Cl(2)] and the other, charged square basis pyramida [Cu(Imz)(4)Cl](+). The 2-hydroxyhippuric acid, which here acts as a counter ion, is deprotonated at its carboxylic group. Cobalt(III) ion in [Co(2-OH-Hip)(Imz)(3)].H(2)O is at the center of an octahedral environment, coordinated to three Imidazol ligands and to a triply deprotonated 2-hydroxyhippuric acid molecule acting as a tridentate ligand. Aqueous solution equilibrium of the quaternary system Cu(2+)/2-OH-Hip/Imz/H(+) was studied by potentiometric titrations.     

Synthesis, characterization, X-ray structure and DNA photocleavage by cis-dichloro bis(diimine) Co(III) complexes

Complexes of the type [Co(LL)2Cl2]Cl, where LL = N,N'-ethylenediamine (en), 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), 1,10-phenanthroline-5,6-dione (phendione) and dipyrido[3,2-a:2',3'-c]phenazine (dppz) have been synthesized and characterized by elemental analyses, IR, UV-visible and NMR spectroscopy. Crystal structure of [Co(phendione)2Cl2]Cl x 0.5 HCl x 3.5 H2O has been solved and refined to R = 0.0552. The crystal is monoclinic with space group C2/c; a = 25.730(2) A, b = 12.375(1) A, c = 18.979(2) A, beta = 119.925(1) degrees and Z = 8. The DNA binding characteristics of the complexes, investigated by covalent binding assay, viscosity measurements and competitive binding fluorescence measurements show that the complexes interact with DNA covalently except the complex containing the planar dppz ligand which intercalates within the base pairs of DNA. The complexes containing en, phen and phendione cleave plasmid pBR 322 DNA upon irradiation under aerobic conditions while the complex containing the dppz ligand cleaves DNA upon irradiation under inert atmosphere. Molecular modeling studies show that the minimized structure of [Co(phendione)2Cl2]+, maintained the octahedral structure while binding to the N7 of guanines and the ligand fits into the major groove without disrupting the helical structure of the B-DNA.     

Synthesis,characterization and antitumor activity of novel octahedral Pt(IV) complexes

Novel platinum(IV) complexes were synthesized having octahedral structure for new antitumor agents. The series of (1,4-butanediamine)Pt(IV) complexes of the type trans,cis-[PtA(2)Cl(2)(1,4-butanediamine)] (A=hydroxo 9, acetato 12, trifluoroacetato 13 as axial ligands) and trans-[PtA(2)(malonate)(1,4-butanediamine)] (A=hydroxo 16, acetato 17, trifluoroacetato 18) were synthesized and characterized by IR, NMR and elemental analysis. The molecular structures of 12, 13 and 18 have been determined by X-ray diffraction methods. The crystals are monoclinic, P2 1/c with a=21.165 (5), b=9.050 (3), c=15.293 (3) A, beta=103.89 (2) degrees and Z=8 for 12, a=10.178 (5), b=12.894 (9), c=12.182 (8) A, beta=91.01 (5) degrees and Z=4 for 13 and a=10.460 (5), b=11.199 (8), c=15.641 (7) A, beta=98.41 (5) degrees, Z=4 for 18. Three crystallographically independent molecules of 12, 13 and 18 have octahedral coordination around Pt(IV) cation. The trans,cis-[PtA(2)Cl(2)(1,4-butanediamine)] were prepared by acetylation or trifluoroacetylation of trans,cis-[Pt(OH)(2)Cl(2)(1,4-butanediamine)]. The trans-[PtA(2)malonate(1,4-butanediamine)] 17 and 18 was prepared by a similar method. The in vitro cytotoxicity of theses Pt(IV) complexes have been evaluated against 12 cancer cell lines assayed by MTS method. The IC(50) values of the compounds 12 and 13 were shown to be lower than those of cisplatin. The in vivo antitumor activity of the Pt(IV) complexes was evaluated using mice bearing L1210 leukemia, B16 melanoma and L1210/cis-DDP cancer animal models. The compound 18 was found to highest activity against cisplatin-resistant cancer cells, L1210/cis-DDP, in vivo.     

Ethylenediamine-palladium(II) complexes with pyridine and its derivatives: synthesis, molecular structure and initial antitumor studies.

The synthesis of four mononuclear palladium complexes of general formula [Pd(en)Cl(L)]NO3 (en = ethylenediamine; L = pyridine (I), 4-methylpyridine (II), 4-hydroxypyridine (III) or 4-aminopyridine (IV) has been achieved. The structure of these compounds was studied by elemental analysis, IR, far-IR and 1H NMR; complex I was analyzed by X-ray diffraction. The crystal of [Pd(en)(pyridine)Cl]NO3 is monoclinic, space group P21/c (a = 7.990(2), b = 16.058(3), c = 9.846(2) A, beta = 103.81(3) degrees, Z = 4, R = 0.067, Rw = 0.066). The Pd(II) atom exhibits an approximately square planar coordination with bond lengths in the range 2.017-2.042 A for Pd-N and 2.320 A for Pd-Cl. In order to determine the donor strength of the aromatic pyridine ligands, the stability constants of binary complex ML2+ (M = [Pd(en) (H2O)2]2+; L = pyridine, 4-Me-pyridine, 4-OH-pyridine and 4-NH2-pyridine) were determined by potentiometric pH titration in aqueous solution (T = 25 degrees C, I = 0.1 mol l-1 NaNO3). The results show that the stability constants of the binary complexes systematically increase with increasing pKa of the pyridines. The above four palladium complexes, [Pt(en)(pyridine)Cl]NO3 and cis-diamminedichloroplatinum (II) (cis-DDP) were assayed for cytotoxicity in vitro against the human leukemia cell line HL-60, and compounds I, II, III and cis-DDP show significant cytotoxic activity against HL-60.     

Structural and functional models for the dinuclear copper active site in catechol oxidases. Synthesis,X-ray crystal structures,magnetic and spectroscopic properties of mu-methoxo-bridged dinuclear copper(II) complexes with N-substituted sulfonamide ligands

Two new mu-methoxo-bridged dinuclear copper(II) complexes with a N-substituted sulfonamide, [Cu(mu-OMe)(L)(NH(3))](2) (1) and [Cu(mu-OMe)(L)(DMSO)](2) (2) [HL, N-2-(4-methylbenzothiazole)benzenesulfonamide], have been prepared and characterized by single-crystal X-ray difraction analyses. Compound 1 crystallizes in the monoclinic space group C(2)/c with a=22.0678(18), b=7.9134(7), c=21.1186(18)A, beta=113.788(4) degrees and Z=8. Compound 2 crystallizes in the monoclinic space group C(2)/c with a=18.0900(10), b=9.5720(10), c=24.2620(10) A, beta=98.7120(10) degrees and Z=8. In both complexes the copper atoms have square-planar environments bridged by two oxygen atoms from methoxide groups. Magnetic susceptibility measurements indicate a very strong antiferromagnetic coupling between the copper(II) ions in both complexes (2J<-1000 cm(-1)). Electronic Paramagnetic Resonance (EPR) spectra of the two complexes both in solid and in solution are silent. 13C NMR spectra of the complexes in solid state have been studied. The complexes have been evaluated as model systems for the catechol oxidase enzyme using 3,5-di-tert-butylcatechol as the test substrate. Complex 2 is slightly more active than complex 1.     

Preparation,characterization, and antitumor activity of new cisplatin analogues with 1-methyl-4-(methylamino)piperidine: crystal structure of [PtII(1-methyl-4-(methylamino) piperidine)(oxalate)

A series of new platinum(II) complexes of the type [Pt(II)(mmap)X] (where mmap, 1-methyl-4-(methylamino)piperidine and X, 1,1-cyclobutanedicarboxylato (CBDCA), oxalato, malonato, methylmalonato, dimethylmalonato, ethylmalonato, diethylmalonato or 2,3-naphthalene dicarboxylato (NDCA)) have been synthesized and characterized by elemental analysis, infrared (IR), and 13C and 195Pt nuclear magnetic resonance (NMR) spectroscopy. The crystal structure of the analogue [Pt(II)(mmap)(oxalate)] was determined using the single crystal X-ray diffraction method. Based upon a total of 4964 collected reflections, we determined that the compound crystallizes in the monoclinic space group P2(1)/c (with a=11.890(2) A, b=9.6695(19) A, c=9.875(2) A, beta=102.03(3) degrees, Z=4, and R=0.0428). In this complex, platinum has a slightly distorted square planar geometry with the two adjacent corners being occupied by two nitrogen atoms of the mmap ligand, whereas the remaining cis positions are occupied by two oxygen atoms of the oxalate molecule. The mmap ligand is in a boat conformation and forms six-membered chelating rings as well as the oxalate molecule forms five-membered chelating rings with platinum. The complexes were evaluated for their cytotoxic potential against the sensitive A2780 tumor model and cisplatin-resistant clone derived in vitro from potential cells.     

Copper(II) complexes of tridentate pyridylmethylethylenediamines: role of ligand steric hindrance on DNA binding and cleavage

Copper(II) complexes of three linear unsymmetrical tridentate ligands viz. N-methyl-N'-(pyrid-2-ylmethyl)ethylenediamine (L1), N,N-dimethyl-N'-(pyrid-2-ylmethyl)ethylenediamine (L2) and N,N-dimethyl-N'-((6-methyl)pyrid-2-ylmethyl)ethylenediamine (L3) have been isolated and characterized by elemental analysis, electronic absorption and EPR spectroscopy and cyclic and differential pulse voltammetry. Of these complexes [Cu(L2)Cl2] and [Cu(L3)Cl2] have been structurally characterized by X-ray crystallography. The [Cu(L2)Cl2] complex crystallizes in the monoclinic space group P2(1)/n with a=11.566(2) A, b=7.369(1) A, c=15.703(3) A, alpha=90 degrees , beta=109.68(8) degrees , gamma=90 degrees and Z=4 while [Cu(L3)Cl2] crystallizes in the triclinic space group P1 with a=9.191(2) A, b=12.359(3) A, c=14.880(3) A, alpha=79.61(13) degrees , beta=86.64(13) degrees , gamma=87.28(8) degrees and Z=2. The coordination geometries around copper (II) in these two complexes are best described as trigonal bipyramidal distorted square based pyramidal (TBDSBP). The distorted CuN3Cl basal plane in them is comprised of three nitrogen atoms of the meridionally coordinated ligand and a chloride ion and the axial position is occupied by the other chloride ion. The interaction of these complexes with Calf Thymus DNA (CT DNA) has been studied by using absorption, emission and circular dichroic spectral methods, thermal denaturation studies, viscometry and cyclic and differential pulse voltammetry. A strong blueshift in the ligand field band and a redshift in the ligand based bands of the copper(II) complexes on binding to DNA imply a covalent mode of DNA binding of the complexes, which involves coordination of most possibly guanine N7 nitrogen of DNA to form a CuN4 chromophore. This is supported by studying the interaction of the complexes with N-methylimidazole (N-meim), guanosine monophosphate (GMP), adenosine monophosphate (AMP) and cytidine (cytd) by ligand field and EPR spectral methods, which indicate the formation of a CuN4 chromophore only in the case of the more basic N-meim and GMP. The DNA melting curves obtained in the presence of copper(II) complexes reveal a monophasic and irreversible melting of the DNA strands and the high positive DeltaTm values (12-21 degrees C) also support the formation of strong Cu-N bonds by the complexes with DNA, leading to intra- and/or interstrand crosslinking of DNA. Competitive ethidium bromide (EthBr) binding studies show that the L2 and L3 complexes are less efficient than the L1 complex in quenching EthBr emission, which is consistent with their forming DNA crosslinking preventing the displacement of the DNA-bound EthBr. A very slight decrease in relative viscosity of DNA is observed on treating the L1 and L2 complexes with CT DNA; however, a relatively significant decrease is observed for the L3 complex suggesting that the length of the DNA fiber is shortened. DNA cleavage experiments show that all the complexes induce the cleavage of pBR322 plasmid DNA, the complex of L1 being more efficient than those of sterically hindered L2 and L3 ligands.     

Interactions of metal ions with a 2,4-diaminopyrimidine derivative (trimethoprim). Antibacterial studies

The interaction of copper (II), zinc(II) and cadmium(II) with Trimethoprim (2,4-diamino-5-(3',4',5'-trimethoxybenzyl) pyrimidine) has been studied. The crystal structures of [Zn(Trim)2Cl2] (2) and [Cd(Trim)Cl2(CH3OH)]n (4) are reported. Compound (2) exhibits a distorted tetrahedral environment around the metal center and crystallizes in the triclinic space group P1 with a=10.2397(6), b=10.4500(6), c=16.3336(16) A, alpha=96.141(8), beta=106.085(5), gamma=96.551(5) degrees and Z=2. In complex (4), the Cd(II) centers are bridged sequentially by two chlorine ions to form infinite chains and present a six-coordinated environment; the compound crystallizes in the monoclinic P2(1)/C space group with a=13.958(5), b=7.532(2), c=18.390(2) A, alpha=90, beta=97.32(5), gamma=90 degrees and Z=4. In both structures the Trimethoprim acts as a monodentate ligand through the pyrimidinic nitrogen N(1) atom. The characterization of the Cu(Trim)2(CH3O)(ClO4) complex through EPR and magnetic measurements suggests a binuclear or polinuclear nature, with bridging methoxo groups. The complexes were screened for their activity against several bacteria, showing activity similar to that of trimethoprim.     

Synthesis, characterization and cytotoxicity of new platinum(IV) axial carboxylate complexes: crystal structure of potential antitumor agent [PtIV(trans-1R,2R-diaminocyclohexane)trans(acetate)2Cl2

A series of new platinum(IV) complexes of the type [PtIV(DACH)trans(L)2Cl2] (where DACH = trans-1R,2R-diaminocyclohexane, and L = acetate, propionate, butyrate, valerate, hexanoate, or heptanoate) bearing the carboxylate groups in the axial positions have been synthesized and characterized by elemental analysis, IR, and 195Pt NMR spectroscopy. The crystal structure of the analogue [PtIV(DACH)trans(acetate)2Cl2] was determined by single crystal X-ray diffraction method. There were two crystallographically independent molecules, both of which lie on crystallographic two-fold axes. The bond lengths and bond angles of both the molecules were the same within the experimental error. The compound crystallizes in the monoclinic space group C2, with a = 11.180(2) A, b = 14.736(3) A, c = 10.644(2) A, beta = 112.38(3) degrees, Z = 4 and R = 0.0336, based upon a total of 1648 collected reflections. In this complex, the platinum had a slightly distorted octahedron geometry owing to the presence of a geometrically strained five-member ring. The two adjacent corners of the platinum plane were occupied by the two amino nitrogens of DACH, whereas the other two equatorial positions were occupied by two chloride ions. The remaining two axial positions were occupied by the oxygens of acetate ligands. The DACH ring was in a chair configuration. An intricate network of intermolecular hydrogen bonds held the crystal lattice together. These analogues were evaluated in vitro and demonstrated cytotoxic activity against the human ovarian 2008 tumor cell line (IC50 = 0.001-0.06 microM). Structure-activity study revealed that activity was highest for the analogue where L = butyrate.     

Synthesis, structural, physico-chemical and biological properties of new palladium(II) complexes with 2,6-dimethyl-4-nitropyridine

This paper describes the synthesis and properties of two new palladium(II) complexes with 2,6-dimethyl-4-nitro-pyridine (dmnp): mononuclear [Pd(dmnp)2Cl2] and dinuclear [Pd2(dmnp)2Cl4]. Complexes were characterized on the basis of chemical and chromatographic analyses, MS and conductometric measurements, as well as by IR and NMR (1H and 13C) spectral studies. The crystal structures of ligand and mononuclear complex, trans-dichlorobis(2,6-dimethyl-4-nitro-pyridine)palladium(II), were determined by three-dimensional X-ray methods. The crystals of both compounds are monoclinic, space groups P21/c with a=19.075(4), b=5.419(1), c=15.045(3) A and beta=108.15(3)degrees for (dmnp), and a=7.544(2), b=14.509(3), c=8.032(2) A and beta=90.32(3)degrees for [Pd(dmnp)2Cl2]. In the (dmnp) there are two crystallographically independent molecules in the unit cell. The nitro groups and methyl C atoms are coplanar with the ring plane. The hydrogen bond of the type C-H...O links the molecules into pairs around center of symmetry. These dimers are held together by contacts of the van der Waals type. In the crystal structure of [Pd(dmnp)2Cl2] the Pd atom lies on an inversion center and is four-coordinated by two pyridine N atoms and by two Cl atoms in trans positions. The coordination geometry is square-planar, with Pd-N and Pd-Cl distances of 2.033(2) and 2.311(1) A, respectively. The two pyridine rings are mutually parallel, but they are twisted from the PdN2Cl2 coordination plane by about 88.5degrees. The preliminary assessments of anti-tumor properties of both complexes and ligand were evaluated as in vitro anti-proliferative activity in four human cancer cell lines: SW707 (adenocarcinoma of the rectum), T47D (breast cancer), HCV (bladder cancer) and A549 (non-small cell lung carcinoma). The [Pd(dmnp)2Cl2] exhibits strong cytotoxic activity against all cell lines whereas the free ligand and dinuclear [Pd2(dmnp)2Cl4] are only moderate active.     

A circular dichroism study of DNA.platinum complexes. Differentiation between monofunctional, cis-bidentate and trans-bidentate platinum fixation on a series of DNAs

The circular dichroism (CD) spectra of a series of DNA . platinum complexes are presented. The following platinum compounds, [Pt(dien)Cl]Cl, cis-Pt(NH3)2Cl2, cis-Pt(en)Cl2, trans-Pt-(NH3)2Cl2, K[Pt(NH3)Cl3] and K2[PtCl4] were complexed with the DNA extracted from bacteria Micrococcus lysodeikticus (72% dG + dC), Escherichia coli (50% dG + dC), Clostridium perfringens (32% dG + dC) and salmon sperm (41% dG + dC). Strong differences were found between the different DNA . Pt complexes. Three types of spectra clearly demonstrate the different platinum binding modes on DNA. In the first type, the platinum compound, i.e. [Pt(dien)Cl]Cl, is fixed to DNA with only one bond (monofunctional complex formation) and no significant change of the CD positive band of DNA is found. The main feature of the second type is a continuous intensity decrease of the positive band as observed for trans-Pt(NH3)2Cl2 (trans-bidentate complex formation). The third type concerns the cis-bidentate platinum fixation obtained with cis-Pt(NH3)2Cl2, cis-Pt(en)Cl2, K[Pt(NH3)Cl3] and K2[PtCl4]. The CD spectra are in this case characterized by an increase in the positive Cotton effect which is dG + dC-dependent up to an rb value around 0.10 (where rb = number of platinum atoms bound per nucleotide), followed by a decrease until DNA saturation with platinum is reached. A linear decrease in the amplitude of the negative band is detected in all the complexes except in the case of the monofunctional DNA . Pt complexes. For the cis-bidentate and trans-bidentate platinum fixation, a continuous bathochromic shift occurs.     

Cytotoxic activity of platinum (II) complexes with tri-n-butylphosphine. Crystal structure of the dinuclear hydrazine-bridged complex, cis,cis-[PtCl(PBu3n)2(mu-N2H4)PtCl(PBu3n) 2] (ClO4)2.2CHCl3.

A series of platinum(II) tri-n-butylphosphine complexes having the formulas cis-[PtCl2L2], NEt4[PtCl3L], [PtCl(en)L]Cl, [Pt(en)L2](ClO4)2, sym-trans-[Pt2Cl4L2], [Pt2Cl2L4](ClO4)2, trans,trans-[PtCl2L(mu-N2H4)PtCl2L] trans,trans-[PtCl2L(mu-en)PtCl2L], and cis,cis-[PtClL2(mu-N2H4)PtClL2](ClO4)2 (L = tri-n-butylphosphine; en = ethylenediamine) have been synthesized and their cytotoxic activity in vitro and in vivo has been studied. The solution behavior of the novel dinuclear diamine-bridged platinum(II) complexes has been investigated by means of UV and 31P NMR spectroscopy. For the ionic hydrazine compound cis,cis-[PtClL2(mu-N2H4)PtClL2](ClO4)2, an x-ray structure determination is reported. Crystal data: space group P2(1)/a, a = 17.803(1), b = 18.888(3), c = 12.506(3) A, beta = 107.97(2) degrees, Z = 2, R = 0.052, RW = 0.058. The platinum coordination is approximately square-planar, with the bond lengths Pt-Cl = 2.358(5), Pt-N = 2.15(1), Pt-P(trans to Cl) = 2.260(5), and Pt-P(trans to N) = 2.262(6) A. All investigated compounds were cytotoxic in vitro against L1210 cells and showed no cross-resistance to cisplatin. On the other hand, no antitumor activity was observed vs L1210 leucemia in DBA2 mice.     

Structure and conformation on linear peptides. VI. Structure of D,L-alanyl-L,D-norvaline

The dipeptide, (DL)-alanyl-(DL)-norvaline, crystallizes in the monoclinic space group P2(1)/c, with a = 12.559(2)A, b = 5.265(1), c = 16.003(3), beta = 103.53(2) degrees, Z = 4. The structure was solved by direct methods and refined to an R-value of 0.054 for 871 reflections with I greater than 2 sigma. The molecule exists as a zwitterion in the crystal. The peptide unit is trans and shows significant deviations from planarity (delta omega = 12.4 degrees). The peptide backbone adopts an extended conformation. The unit cell contains D-Ala-L-norval and its enantiomer. The molecular conformation and packing features show a striking resemblance to those for D-Ala-L-Met (1), and leads to the speculation that norvaline might act as an analog of methionine.     

Molecular structure, bioavailability and bioactivity of [Cu(o-phen)2(cnge)](NO3)2.2H2O and [Cu(o-phen)(cnge)(H2O)(NO3)2] complexes

Two Cu(II) complexes with cyanoguanidine (cnge) and o-phenanthroline, [Cu(o-phen)(2)(cnge)](NO(3))(2).2H(2)O (1) and [Cu(o-phen)(cnge)(H(2)O)(NO(3))(2)] (2), have been synthesized using different experimental techniques and characterized by elemental analyses, FTIR, diffuse and UV-vis spectra and EPR and magnetic moment measurements techniques. The crystal structures of both complexes were solved by X-ray diffraction methods. Complex (1) crystallizes in the monoclinic space group C2/c with a=12.621(5), b=31.968(3), c=15.39(1)A, beta=111.68(4) degrees, and Z=8 and complex (2) in the monoclinic space group P2(1)/n with a=10.245(1), b=13.923(2), c=12.391(2)A, beta=98.07(1) degrees, and Z=4. The environments of the copper(II) center are trigonal bipyramidal (TBP) for [Cu(o-phen)(2)(cnge)](2+) and an elongated octahedron for [Cu(o-phen)(cnge)(H(2)O)(NO(3))(2)]. Solution studies have been performed to determine the species distribution. The superoxide dismutase (SOD) activities of both complexes have also been tested in order to determine if these compounds mimic the enzymatic action of the enzyme SOD that protects cells against peroxide radicals.