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.     

Preparation, X-ray crystal structure, and 195Pt NMR spectra of platinum(II) with dipeptides and dipeptide methyl esters

Three dipeptide complexes of the form K[M(dipeptide)Cl] (H2dipeptide=glycylbeta-alanine, beta-alanylglycine, beta-alanylbeta-alanine) and four dipeptide methyl ester complexes of the form K[M(dipeptideOMe)Cl2] (HdipeptideOMe=glycylalpha-alanine methyl ester, alpha-alanylglycine methyl ester, dialpha-alanine methyl ester) were newly prepared. The K[Pt(glybeta-ala)Cl] complex crystallizes in the monoclinic space group C2/c with unit cell dimensions of a=25.77(1) A, b=4.09(2) A, c= 16.432(9) A, beta=103.74(4) degrees, and Z=8. The K[Pt(glyalpha-alaOMe)Cl2] complex crystallizes in the monoclinic space group P1 with unit cell dimensions of a=7.195(2) A, b=7.977(5) A, c=10.326(3) A, alpha=72.49(3) degrees, beta=103.74(4) degrees, gamma=88.27(4) degrees and Z=2. The 195Pt NMR peaks of the complexes containing the beta-alanine moiety appeared significantly more upfield than those of the complexes containing diglycine. The ratios of the species of the platinum complexes containing the dipeptide ester in neutral solution were significantly different from those in alkaline solution at 40 degrees C for a short time.     

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.     

Synthesis, X-ray crystal structure and NMR characterisation of mononuclear Pd(II) and Pt(II) complexes of didentate ligands with NN′-donor set

Two new 3,5-dimethylpyrazolic derived ligands that are N1-substituted by diamine chains, 1-[2-(diethylamino)ethyl]-3,5-dimethylpyrazole (L1) and 1-[2-(dioctylamino)ethyl]-3,5-dimethylpyrazole (L2) were synthesised. Reaction of the ligands, L1 and L2, with [MCl₂(CH₃CN)₂] yielded [MCl₂(L)] (M = Pd(II), Pt(II)) complexes. These complexes were characterised by elemental analyses, conductivity measurements, IR, ¹H, ¹³C{¹H} and ¹⁹⁵Pt{¹H} NMR spectroscopies. The crystal structure of [PdCl₂(L1)] was determined by single-crystal X-ray diffraction methods. The structure consists of mononuclear units. The Pd(II) atom is coordinated by a pyrazolic nitrogen, an amine nitrogen and two chlorine atoms in a cis disposition. In this structure, C-H?Cl, C-H?H-C and C-H?C-H intermolecular interactions have been identified.     

Syntheses, crystal structure and cytotoxicity of diamine platinum(II) complexes containing maltol

The cationic complexes (1,2-diaminoethane)(maltolato)platinum(II) ([Pt(en)(ma)]+) and (1R,2R-1,2-diaminocyclohexane)(maltolato)platinum(II) ([Pt(R,R-DACH)(ma)]+) have been prepared and the structure of [Pt(R,R-DACH)(ma)]NO3 has been determined by single crystal X-ray diffraction. The geometry of the metal in [Pt(R,R-DACH)(ma)]NO3 is essentially square planar and the maltolate ligand has a geometry similar to other chelate complexes involving this ligand. The cytotoxicities of the compounds have been assessed in the human cell lines HeLa and K562 and the IC50 values are approximately 32 microM in HeLa cells and 26 microM in K562 cells. In these cell lines the cytotoxicity of cisplatin is higher than the maltolate complexes by a factor of 2 to 3 whereas the cytotoxicity of carboplatin is lower than the maltolate complexes.     

Carbonyl trichlorostannate complexes of platinum: chemistry and 119Sn, 195Pt,and 13C NMR spectroscopy

The reactions of the carbonyl anion [PtCl₃(CO)]^- with SnCl₂ in the presence of CO in both methylene chloride and acetone are reported. In the former solvent, only Pt^II-SnCl₃ species are formed. These have been identified by ¹³C, ¹¹⁹Sn and ¹⁹⁵Pt NMR measurements as cis-[PtCl₂(SnCl₃)(CO)]^-, (I), trans- [PtCl(SnCl₃)₂(CO)]^-, (II), and [Pt(SnCl₃)₄(CO)]^2-, (III). Salts of these complexes have been isolated. In contrast, when acetone is the solvent, reduction of the platinum occurs to give two new complexes. On the basis of NMR measurements, we assign one of these as the Pt^I dimer [Pt₂(SnCl₃)₄(CO)₂]^2-, (IV), and the other as a platinum triangle (VI) containing terminal CO ligands and two types of Sn ligand. The Pt^II compound (IV) can also be generated by treating a CH₂Cl₂ solution of trans-[PtCl(SnCl₃)_2- (CO)]^-, (II), with dihydrogen. NMR spectroscopic data, including those from measurements on samples of the complexes containing ¹³C-enriched CO, are reported and discussed.     

Overall view of the use of chiral platinum(II) complexes as chiral derivatizing agents (CDAs) for the enantiodiscrimination of unsaturated compounds by 195Pt NMR

The use of organometallic CDAs based on ethene-platinum(II) complexes, covalent cis- and trans-dichloro(Am)(ethylene)platinum(II), and ionic [PtCl(3)(C(2)H(4))](-)[AmH](+), containing primary and secondary amines, for the (195)Pt NMR enantiodiscrimination of chiral unsaturated compounds is reviewed.     

Trichloroamine complexes of platinum: preparation,crystal structure and solution behavior of cytosinium trichlorocytosineplatinate(II)

A complex containing a protonated and N3-platinated cytosine (C), [CH][Cl₃Pt(C)] (1a) has been prepared, converted into its K[Cl₃Pt(C)] (1b) and NH₄[Cl₃]Pt(C)]·H₂O (1c) analogs, and structurally characterized (X-ray, Raman, NMR). Reaction of 1b with L = 1-methylcytosine and with L = Me₂SO gave the neutral mixed-ligand complexes cis-Cl₂Pt(C)L. Excess NH₃ was used to convert the anion of 1b into the cation [(NH₃)₃Pt(C)]²⁺ (3a). The pK_a of the N(1)H proton in 3a is 9.4, as determined by UV spectroscopy. The N(1)H is displaced by Pt(II) electrophiles even at neutral pH to give N3,N1-diplatinated cytosinato complexes, as shown by ¹H NMR (³J coupling or ¹⁹⁵Pt at N(1) with H6, 29 Hz, and ⁴J coupling of ¹⁹⁵Pt at N(3) with H5, 14Hz). The results of the X-ray structure determination of 1a (R = 0.031, R_w = 0.034) are of relevance in that they permit a direct comparison of the effect of a proton as opposed to that of a Pt electrophile on the nucleobase geometry. Moreover, the expected decrease in CO(2) bond length as a consequence of Pt binding is observed.     

Synthesis of new platinum(II) compounds with several bidentate and tridentate nitrogen-donor ligands. Structural analyses by H, C{H} and Pt{H} NMR spectroscopy and X-ray crystal structure

The reaction of the N-alkylaminopyrazole (NN′) ligands 1-[2-(ethylamino)ethyl]-3,5-dimethylpyrazole (deae), 1-[2-(tert-butylamino)ethyl]-3,5-dimethylpyrazole (deat), or (NN′N) ligands bis[(3,5-dimethylpyrazolyl)methyl]ethylamine (bdmae) and bis[(3,5-dimethylpyrazolyl)ethyl]ethylamine (ddae) with [PtCl₂(CH₃CN)₂] affords a series of square-planar Pt(II) complexes with formula [PtCl₂(NN′)] (NN′ = deae (1); deat (2)), [PtCl₂(bdmae)] (3), or [PtCl(ddae)]Cl (4). Treatment of complex 4 in the presence of AgBF₄ in CH₂Cl₂/methanol (3:1) gives [PtCl(ddae)](BF₄) (5). These Pt(II) complexes have been characterised by elemental analyses, conductivity measurements and IR, ¹H, ¹³C{¹H}, and ¹⁹⁵Pt{¹H} NMR spectroscopies. The ¹H NMR spectroscopic studies of the complexes prove the rigid conformation of the ligands when they are complexed. The solid-state structure of complex 1 was determined by single crystal X-ray diffraction methods. The deae ligand is coordinated through the N_pz and N_amino atoms to the metallic centre, which completes its coordination with two chlorine atoms in cis disposition.     

Coordination chemistry of higher oxidation states. Part 21. Platinum-195 NMR studies of platinum(II) and platinum(IV) complexes of bi- and multi-dentate phosphorus,arsenic and sulphur ligands

195-Platinum NMR spectra are reported for a series of complexes of bidentate ligands [Pt(LL)X₄] (X=Cl, Br; LL=diphosphine, diarsine, dithioether, diselenoether), [Pt(Me₂PCH₂CH₂PMe₂)₂X₂]X₂, [Pt(o-C₆H₄(AsMe₂)₂)₂X₂]X₂, and for the Pt(II) analogues. The trends in chemical shifts δ(Pt) and ¹J(PtP), ¹J(PtSe) coupling constants are discussed, and used to establish the nature of the solution species obtained by oxidation of Pt(II) complexes of some multidentate phosphorus and arsenic ligands. The [Pt(LL)I₄] materials are shown to exist as [Pt^II(LL)I₂] in dimethylsulphoxide solution, but [Pt(o-C₆H₄(AsMe₂)₂)₂I₂]²⁺ is a genuine Pt(IV) iodo-complex.     

Palladium(II) complexes of 1,10-phenanthroline: Synthesis and X-ray crystal structure determination

Two palladium(II) complexes, [Pd(phen)(NCCH₃)₂][O₃SCF₃]₂ (1) and [Pd(phen)(μ-OH)]₂[O₃SCF₃]₂ · 2H₂O (2) (where phen = 1,10-phenanthroline), have been crystallized following the reaction of Pd(phen)Cl₂ with silver triflate, Ag(O₃SCF₃), in acetonitrile and water, respectively. The structures of both complexes are based on a Pd(phen)²⁺ metal core, with two acetonitrile molecules binding in a monodentate fashion in complex 1 and two hydroxo bridges holding together two cores to form a dimer in complex 2. Additionally, both complexes present a hydrogen bonded 3-D network involving the triflate anions in 1, and water and triflate anions in 2. Both complexes have been characterized by infrared and ¹H NMR spectroscopy and their crystal structures determined by X-ray crystallography.     

NMR and X-ray characterization of a platinum(II) complex with (−)sparteine

A platinum(II) complex containing the diamine (−)sparteine has been synthesized for the first time and fully characterized by ¹H and ¹³C NMR spectroscopy and X-ray crystallography. (−)Sparteine is an alkaloid containing four fused rings and four asymmetric centers of configurations 6R, 7S, 9S, and 11S at the four tertiary carbon atoms. In the cis conformation it can act as a chelating N-donor ligand toward a metal ion. The steric bulkiness of this ligand is such that the Pt-N bond lengths are greater than normal and the angle between the cis-chlorido ligands is well below the theoretical value of 90°. This sparteine complex of platinum appears to be an ideal substrate for investigating the stereochemistry of adducts with nucleotides and DNA. For instance the orientation of a coordinated nucleobase can be determined with precision by monitoring the strength of NOE cross peaks between the sparteine protons pointing toward the metal center and key protons of the coordinated nucleobase(s) (e.g. H8 protons of guanine or adenine).     

Synthesis and characterization of Mg(II), Mn(II), Zn(II) and Cd(II) complexes with a new heptaaza Schiff base pendant-armed macrocycle: X-ray crystal structure, NMR and computational study

New 2-aminoethyl pendant-armed Schiff base macrocyclic complexes, [ML⁷]²⁺ (M = Mn(II), Mg(II), Zn(II) and Cd(II)), have been prepared via M(II) templated [1 + 1] cyclocondensation of 2,6-diacetylpyridine with a new branched hexamine, N,N,N′,N′-tetrakis(2-aminoethyl)-2,2-dimethylpropane-1,3-diamine. The ligand is a 16-membered pentaaza macrocycle having two 2-aminoethyl pendant arms [L⁷ is 2,14-dimethyl-6,10-bis(2-aminoethyl)-3,6,10,13,19-pentaazabicyclo[13.3.1]8,8-dimethylnonadeca-1(19),2,13,15,17-pentaene]. The crystal structures of [MnL⁷]²⁺ and [MgL⁷]²⁺ were determined from X-ray diffraction data. The geometry of the coordination sphere of complexes is a slightly distorted pentagonal bipyramid with the metal ion located within a pentaaza macrocycle and two pendant amines coordinating on opposite sides. All complexes were characterized by IR, microanalysis and except of [MnL⁷]²⁺ by ¹H NMR, ¹³C NMR, DEPT135, COSY(H, H) and HMQC spectroscopy. The data indicate that the structure is pentagonal bipyramidal in each case. The structure of all complexes has also been theoretically studied by ab initio Hartree-Fock and density functional theory methods.     

Preparation and crystal structure of bis(acetato)(trans-1,2-diaminocyclohexane)platinum(II)

The structure of the complex [Pt(trans-1,2-di- aminocyclohexane) (acetate)₂]·H₂O has been determined by X-ray diffraction. This racemic compound is orthorhombic, space group Aba2, a = 20.813(9), b = 7.926(5), c = 17.296(8) Å, Z = 8. The structure was refined on 1214 nonzero Cu Kα reflections to R = 0.028. The square planar environment of Pt includes the amino groups of the diamine in cis positions and oxygens from two monodentate acetates. The PtN and PtO distances average 2.00(3) and 2.02(3) Å, respectively. The bite of the diamine ligand imposes a NPtN angle of 85(1)°, whereas the small OPtO angle of 85(1)° probably results from packing effects. The average plane through the puckered cyclohexyl ring makes an angle of 19° with the PtN₂O₂ plane. The molecules are stacked by pairs along the b axis. The two molecules of each pair are 180° apart about the stacking axis, and form altogether four NH···O hydrogen bonds.     

Preparation, characterization, and antitumor activity of water-soluble aminoalkanol platinum(II) complexes

A new series of highly water-soluble aminoalkanol platinum(II) complexes have been synthesized and characterized by elemental analysis, conductance, IR, and 195Pt NMR. Preliminary in vitro and in vivo screening tests for antitumor activities of these complexes against L1210 murine leukemia were performed. In general, these compounds were far less cytotoxic than cisplatin and possessed only a moderate degree of antitumor activity.     

Synthesis, spectroscopy and antiproliferative activity of cis- and trans-platinum(II) complexes with diethyl (pyridin-4-ylmethyl)phosphate. X-ray crystal structure of trans-Pt(II) complex

Preparations of cis- and trans-platinum(II) complexes of diethyl (pyridin-4-ylmethyl)phosphate (4-pmOpe) have been described. These complexes were identified and characterized by far-IR, 1H NMR, 13C NMR, 31P NMR and 195Pt NMR and microanalyses. The crystal and molecular structure of trans-platinum(II) complex i.e., trans-[PtCl2(4-pmOpe)2] was determined by the X-ray diffraction. Novel complexes were assayed for their potential antiproliferative effect against HT 29 (colorectal adenocarcinoma) and A 549 (non-small cell lung cancer) cell lines as well as normal human peripheral blood lymphocytes. The results obtained indicate that novel analogues of cis-diamminedichloroplatinum(II) cause inhibition of cells growth which suggest that they could be chemotherapeutic drugs in the future.     

Palladium(II) and platinum(II) complexes with polypyridylbenzene ligands

The ligands 1,3-bis(3-pyridyl)benzene (1), 1,3-bis(4-pyridyl)benzene (2) and 1,3,5-tris(4-pyridyl)benzene (3) have been prepared by Stille coupling of 3- or 4-trimethylstannylpyridine with the appropriate bromoarene. Ligands 1 and 2 react with [M(OTf)₂(dppp)] (M=Pd, Pt) to produce the dipalladium- or diplatinum-containing macrocycles [M₂(μ-1)₂(dppp)₂](OTf)₄ or [M₂(μ-2)₂(dppp)₂](OTf)₄. These have been characterized by NMR spectroscopy and mass spectrometry and, in the case of [Pd₂(μ-1)₂(dppp)₂](OTf)₄, by X-ray crystallography. The molecular structure of the [Pd₂(μ-1)₂(dppp)₂]⁴⁺ cation reveals a shallow arrangement of the aromatic rings, with the palladium atoms lying above and below. The tridentate ligand 3 reacts with [Pd(OTf)₂(dppp)] to produce a trimetallic species of the form [Pd₃(μ₃-3)₂(dppp)₃](OTf)₆.     

Synthesis, spectroscopy, structure and photophysical properties of dinaphthylmethylarsine complexes of palladium(II) and platinum(II)

Dinaphthylmethylarsine complexes of palladium(II) and platinum(II) with the formulae [MX₂L₂] (M = Pd, Pt; L = di(1-naphthyl)methylarsine = Nap₂AsMe and X = Cl, Br, I), [M₂Cl₂(μ-Cl)₂L₂], [PdCl(S₂CNEt₂)L], [Pd₂Cl₂(μ-OAc)₂L₂] and [MCl₂(PR₃)L] (PR₃ = PEt₃, PPr₃, PBu₃, PMePh₂) have been prepared. These complexes have been characterized by elemental analyses, IR, Raman, NMR (¹H, ¹³C, ³¹P) and UV-vis spectroscopy. The stereochemistry of the complexes has been deduced from the spectroscopic data. The crystal structures of trans-[PdCl₂(PEt₃)(Nap₂AsMe)] and of [Pd(S₂CNEt₂)₂], a follow-up product, were determined. The UV-vis spectra of [MX₂L₂] complexes show a red shift on going from X = Cl to X = I. The complexes [PdX₂L₂] and [PtX₂L₂] are strongly luminescent in fluid solution and in the solid at ambient temperature.     

Enantiopure platinum(II) complexes with chiral diphosphine and diphosphinite ligands derived from 2,2-biphosphole: Synthesis, crystal structure and catalysis

Enantiopure platinum(II) complexes have been synthetized with chiral stereodynamic diphosphine and diphosphinite ligands derived from 2,2-biphosphole through a dynamic chirality control upon coordination. Catalytic performances of these platinum complexes have been explored in asymmetric hydroformylation. All complexes proved to be effective catalysts with respect to chemoselectivity and regioselectivity but induced only low enantioselectivities.     

Synthesis and characterization of nitroimidazole complexes of platinum and palladium and the crystal and molecular structure of trans-dichlorobis(misonidazole)platinum(II)

The synthesis and properties of some nitroimidazole complexes of platinum and palladium starting from the MCl₄^2- salts are described. Both 5-NO₂-imidazole and metronidazole give cis-[MCl₂L₂] complexes whereas trans-[MCl₂L₂] is obtained for 2-NO₂-imidazole and misonidazole. The crystal structure of trans-dichlorobis(misonidazole)platinum(II) was determined by three-dimensional X-ray methods. The compound crystallized in space group P2₁/c in discrete monomeric units with a = 11.303(5), b = 13.002(5) and c = 8.125(3) Å, B = 91.39(3)°, Z = 2 and the observed and calculated densities are 1.83 and 1.859 respectively. The final full-matrix least-squares refinement gave values of R₁ = 0.037 and R₂ = 0.045 for 142 variables. The complex is square-planar with Pt-Cl and Pt-N distances of 2.294(3) and 2.016(9) Å respectively. The mean plane of the misonidazole ring is twisted 56° with respect to the PtCl₂L₂ square plane and the Cl-Pt-N angles are 89.4(3) and 90.6(3)°; the nitro group also lies out of the plane of the misonidazole ring. The closest nonbonded contact between non-hydrogen atoms in the unit cells is 2.80 Å suggesting hydrogen bonding between the hydroxyl proton and the ether oxygen in the misonidazole side-chain, i.e. O-H?O. Aspects of the chemistry of these species in relation to their biological activity are discussed.