13C magnetic resonance investigation of mercury (II) binding to nucleosides and thiolated nucleosides in dimethyl sulfoxide.

Natural abundance, proton-decoupled 13C magnetic resonance spectroscopy is shown to be a useful technique for identifying the mercury (II) binding sites on nucleosides and especially thiolated nucleosides. Measurements made on dimethyl sulfoxide-d6 solutions, 0.5 M in nucleoside and 0.15 M in mercury, reveal that both CH3 HgCl and HgCl2 bind principally to the sulfur atoms of s6 Guo and s8 Guo. The 13C NMR spectra of the unthiolated nucleosides in the presence of excess (4:1) mercury reveal that HgCl2 binds to N-3 of cytidine, to more than one site on adenosine and guanosine, but not strongly to uridine. Excess HgCl2 shifts the thiocarbonyl carbon atoms in s6 Guo and s8 Guo approx. 16 ppm upfield compared to the free nucleosides, and there is evidence for additional coordination to N-7 of s6 Guo. Binding to the ribose hydroxyl groups is clearly ruled out. At least in these instances, 13C NMR proves to be useful for assigning the mercury (II) binding sites, complementing the results of proton magnetic resonance studies. Proton NMR data for the binding of CH3 HgCl and HgCl2 to s6 Guo and s8 Guo are also presented.     

Multinuclear NMR spectroscopy and antitumor activity of novel platinum(II) complexes with 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidines

Novel platinum(II) complexes with 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidines have been synthesized and characterized by infrared and multinuclear magnetic resonance spectroscopic techniques (1H, 13C, 15N, 195Pt). The complexes are of two types: [PtCl2(L)2] and [PtCl2(NH3)(L)], where L=5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine (dptp) and 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp). Significant 15N NMR upfield shifts (92-95 ppm) were observed for N(3) atom indicating this nitrogen atom as a coordination site. The molecular structure suggest that Pt(II) ion has the square planar geometry with N(3) bonded 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidines, N-bonded second ligand (NH3 for cis-[PtCl2(NH3)(L)] or, respectively, 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidines for cis-[PtCl2L2]) and two cis chloride anions. The antiproliferative activity in vitro of complexes (1-4) have been tested against the cells of four human cell lines: SW707 rectal adenocarcinoma, A549 non-small cell lung carcinoma, T47D breast cancer and HCV29T bladder cancer. The results indicate a moderate antiproliferative activity of (4) against the cells of rectal, breast and bladder cancer and a marked and selective cytotoxic effect of (1-3) against the cells of all studied human cancer lines.     

Heavy metal-nucleoside interactions. Binding of methylmercury(II) to inosine and catalysis of the isotopic exchange of the C-8 hydrogen studied by 1-H nuclear magnetic resonance and raman difference spectrophotometry.

Raman difference spectrophotometry reveals that CH3HgII binds quantitatively to N(1) of inosine at pH 8, substituting for the proton. When N(1) is saturated, binding occurs at a second site. Measurements of the 1-H nuclear magnetic resonance spectra of both inosine and of CH3Hg-II are in agreement with the N(1) binding and indicate that the second site for mercuriation is N(7). This second binding reaction is observed to increase the rate of exchange of the C(8) hydrogen with solvent, consistent with results observed for alkylation at N(7). Coordination of the electrophilic CH3Hg-II to N(7) increases the acidity of H(8), facilitating OHminus--catalyzed proton abstraction and reprotonation by themedium. For comparison, the reaction of CH3Hg-II with [8-2-H]inosine has been studied. Displacement of the N(1) hydrogen upon mercuriation of inosine causes a significant electron delocalization into the ring, increasing the basicity of N(7), and accounting for the synergic effect in metal binding observed originally by Simpson. In contrast, 1-methylinosine interacts only slightly with CH3Hg-II at pH 8. Coordination appears to be at N(7), since H(8) again is observed to exchange rapidly with solvent protons. In acidic solution, pH less than 2, binding to inosine is almost quantitative and exclusively to N(7). The behavior of CH3Hg-II is compared with that of Pt(II) and with Ni(II), Co(II), AND Zn(II). A brief comparison is made among ultraviolet absorption spectrophotometry, nuclear magnetic resonance (NMR), and Raman difference spectrophotometry for studying reactions of nucleosides and nucleotides.     

Interaction of the anti-tumour drug cis-Pt(en)Cl2 with Cytidilyl-3'--5'-guanosine

Chemical shifts occurring in 1H nuclear magnetic resonance and Sephadex G 25 chromatography are used to follow the reaction of the dinucleotide C3'p5'G (cytidilyl-3'phosphate5'-guanosine) in aqueous solution and to separate its products. Binding of the platinum occurs in first place at the cytosine, then at the guanine base. Two major complexes are produced, Pt:CpG and (Pt:CpG)2, which account for respectively for an internal and an external cross-linking effect.     

Nuclear magnetic resonance studies of the old yellow enzyme. 2. 13C NMR of the enzyme recombined with 13C-labeled flavin mononucleotides

The apoenzyme of NADPH oxidoreductase, 'old yellow enzyme', was reconstituted with selectively 13C-enriched flavin mononucleotides and investigated by 13C NMR spectroscopy. The 13C NMR results confirm the results obtained by 15N NMR spectroscopy and yield additional information about the coenzyme-apoenzyme interaction. A strong deshielding of the C(2) and C(4) atoms of enzyme-bound FMN both in the oxidized and reduced state is observed, which is supposed to be induced by hydrogen-bond formation between the protein and the two carbonyl groups at C(2) and C(4) of the isoalloxazine ring system. The chemical shifts of all 13C resonances of the flavin in the two-electron-reduced state indicate that the N(5) atom is sp3-hybridized. From 31P NMR measurements it is concluded that the FMN phosphate group is not accessible to bulk solvent. The unusual 31P chemical shift of FMN in old yellow enzyme seems to indicate a different binding mode of the FMN phosphate group in this enzyme as compared to the flavodoxins. The 13C and 15N NMR data on the old-yellow-enzyme--phenolate complexes show that the atoms of the phenolate are more deshielded whereas the atoms of the enzyme-bound isoalloxazine ring are more shielded upon complexation. A non-linear correlation exists between the chemical shifts of the N(5) and the N(10) atoms and the pKa value of the phenolate derivative bound to the protein. Since the chemical shifts of N(5), N(10) and C(4a) are influenced most on complexation it is suggested that the phenolate is bound near the pyrazine ring of the isoalloxazine system. 15N NMR studies on the complex between FMN and 2-aminobenzoic acid indicate that the structure of this complex differs from that of the old-yellow-enzyme--phenolate complexes.     

X-ray photoelectron spectroscopy of DNA-Pt complexes. Evidence of O6 (Gua)-N7 (Gua) chelation of DNA with cis- dichlorodiamine platinum(II).

The binding energies of nitrogen, oxygen, phosphorus, chlorine and Pt in several DNA - Pt (II) complexes are reported and discussed. The nitrogen band of DNA is slightly shifted upon complexation with Pt. Oxygen binding energies in the complexes studied clearly show that cis-Pt(NH3)2Cl2 forms a specific chelate N7(Gua) - O6 (Gua) with DNA as opposed to trans-Pt(NH3)2Cl2 and the other Pt compounds which react only with the N7(Gua) site of DNA.     

Cu, Pt, and Pd complexes of the 3-deoxy-1,2-bis(thiosemicarbazone) derived from D-glucose

3-Deoxy-D-erythro-hexos-2-ulose bis(thiosemicarbazone) (1) acts as a tetradentate ligand of the N2S2 type which forms stable coordination complexes with metal(II) cations. The Cu(II), Pt(II), and Pd(II) chelates (2, 4, and 6, respectively) of 1 were synthesized and characterized by elemental analysis and NMR spectroscopy. The NMR spectra of the Pt complex (4) showed the coupling of H-1 and C-1, C-2 of the bis(thiosemicarbazone) with 195Pt (33.7% naturally occurring), which supports the structure proposed for the chelate. The complexes 2, 4, and 6 were acetylated to give the corresponding tri-O-acetyl derivatives 3, 5, and 7. Elimination of Cu(II) from 3 with hydrogen sulfide afforded 8, the tri-O-acetyl derivative of 1. Preliminary studies have shown antiviral activity of chelates 2, 4, and 6 against poliovirus type 1.     

Actinomycin D-deoxynucleotide complexes as models for the actinomycin D-DNA complex. The use of nuclear magnetic resonance to determine the stoichiometry and the geometry of the complexes.

The use of proton and carbon-13 magnetic resonance spectroscopy for the determination of the geometry and the stoichiometry of the actinomycin D-deoxyguanosine 5'-monophosphate complex is outlined. The dimerization of actinomycin D has been reexamined by recording the proton magnetic resonance spectrum of actinomycin D to much lower concentrations through the use of Fourier transform nuclear magnetic resonance techniques. The effect of the actinomycin D dimerization on the observed chemical shifts that results from the additon of nucleotides to an actinomycin D solution is directly demonstrated by comparing the actinomycin D-nucleotide titrations at both low (approximately 0.3 mM) and high (approximately 12 mM) concentrations of actinomycin D. In the presence of excess nucleotide the chemical shifts of the actinomycin D groups were essentially the same for both the low and high concentration titrations. The complexes of actinomycin D with pdG-dC, dG-dC, deoxyguanosine 3'-monophosphate, G-C, C-G, dIMP(5'), 2, 6-diaminopurine deoxyribose, and other nucleotides were also investigated by proton magnetic resonance and visible spectral titrations. These data were interpreted in terms of the molecular geometry of the complexes and in terms of the effect of the structure of the nucleotide base on the relative binding affinity of the nucleotides for the two nucleotide binding sites of actinomycin D. The carbon-13 chemical shifts of dGMP(5') were measured as a function of concentration over the concentration range of 0.5-0.025 M. The infinite dilution carbon-13 chemical shifts were graphically estimated from the dilution curves. These values were used to calculate the changes in the chemical shifts of the dGMP carbons that result from the formation of an actinomycin D-(dGMP)2 complex. It was not possible to interpret these carbon-13 chemical shift changes in terms of only ring current effects, which thus rules out the use of carbon-13 spectroscopy in the determination of the geometries of the actinomycin D complexes with the mono- and dinucleotides. The induced chemical shifts in the proton spectra may be used in the determination of the geometries of the complexes. A consideration of these data for the above nucleotide series shows that the predominant complex formed is one in which the guanine rings in the two nucleotide binding sites of actinomycin D are oriented in a manner very similar to that observed in the cocrystalline complex of actinomycin D with deoxyguanosine.     

Kinetics and mechanism of the substitution reactions of [PtCl(bpma)]<Superscript>+</Superscript>, [PtCl(gly-met-<Emphasis Type="Italic">S,N,N</Emphasis>)] and their aqua analogues with <Emphasis Type="SmallCaps">l</Emphasis>-methionine,glutathione and 5′-GMP

The substitution reactions of [PtCl(bpma)]+, [PtCl(gly-met-S,N,N)], [Pt(bpma)(H(2)O)](2+) and [Pt(gly-met-S,N,N)(H(2)O)](+) [where bpma is bis(2-pyridylmethyl)amine and gly-met-S,N,N is glycylmethionine] with L-methionine, glutathione and guanosine 5'-monophosphate (5'-GMP) were studied in aqueous solutions in 0.10 M NaClO(4) under pseudo-first-order conditions as a function of concentration and temperature using UV-vis spectrophotometry. The reactions of the chloro complexes were followed in the presence of 10 mM NaCl and at pH approximately 5, whereas the reactions of the aqua complexes were studied at pH 2.5. The [PtCl(bpma)]+ complex is more reactive towards the chosen nucleophiles than [PtCl(gly-met-S,N,N)]. Also, the aqua complexes are more reactive than the corresponding chloro complexes. The activation parameters for all the reactions studied suggest an associative substitution mechanism. The reactions of [PtCl(bpma)]+ and [PtCl(gly-met-S,N,N)] with 5'-GMP were studied by using (1)H NMR spectroscopy at 298 K. The pK (a) value of the [Pt(gly-met-S,N,N)(H(2)O)]+ complex is 5.95. Density functional theory calculations (B3LYP/LANL2DZp) show that in all cases guanine coordination to the L(3)Pt fragment (L(3) is terpyridine, bpma, diethylenetriamine, gly-met-S,N,N) is much more favorable than the thioether-coordinated form. The calculations collectively support the experimentally observed substitution of thioethers from Pt(II) complexes by N7-GMP. This study throws more light on the mechanistic behavior of platinum antitumor complexes.     

The interaction of metal ions with nucleic acids. Ternary complexes of copper(II) with peptides and nucleosides

Difference electronic absorption and electron paramagnetic resonance spectroscopy were used to monitor the formation of the ternary complexes of Cu(II) ions with nucleosides and dipeptides containing Gly, Leu and Trp residues. Stability constants of these mixed-ligand complexes of Cu(II)-peptides with nucleosides were found to decrease in the following order: 6-ketopurines greater than 6-aminopurine greater than pyrimidines. Interpretation of the EPR data indicated that the covalent nature of the copper-ligand bond also decreases in the same order. The EPR findings suggest that nucleosides are bonded in the equatorial position of the Cu(II)-peptide complexes, however, in the case of pyrimidine nucleosides weak axial bonding also seems to occur.     

Synthesis,characterization and antitumor activity of a series of N-substituted iminodiacetato(diammine) platinum(II) complexes

A series of water-soluble N-substituted iminodiacetato (diammine)platinum(II) complexes [Pt(NRIDA)(NH₃)₂] have been synthesized and characterized by measurement of physical properties (conductivity and pH) and by various spectroscopic techniques (infrared, ¹H and ¹³C{¹H} nuclear magnetic resonance). The iminodiacetate ligand is coordinated to platinum through an O,N linkage. The results obtained suggest that these complexes are relatively stable for more than 24 h in aqueous solution. Preliminary in vitro and in vivo screening test for antitumor activity of these complexes against L1210 murine leukemia were performed. Many of complexes had acceptable in vitro cytotoxicity, but none displayed a significant level of in vivo antitumor efficacy.     

Synthesis, multinuclear magnetic resonance and crystal structures of Pt(II) complexes containing amines and bidentate carboxylate ligands

A novel synthetic method for the synthesis of the complexes cis-Pt(amine)₂R(COO)₂ is compared to two other methods involving the use of either barium dicarboxylate or sodium carboxylate. Pt(II) compounds with monodentate and bidentate amines were studied. The reaction involves the use of a silver dicarboxylato complex, which is the intermediate in the new synthetic procedure. The crystal structure of the silver intermediate with the ligand 1,1-cyclobutanedicarboxylate (1,1-CBDCA) was determined by X-ray diffraction. The crystal Ag₂(1,1-CBDCA) has a very interesting 3-D extended structure. The complexes cis-Pt(amine)₂R(COO)₂ were studied in solution by multinuclear (¹H, ¹³C and ¹⁹⁵Pt) magnetic resonance spectroscopy, but the solubilities are very low. D₂O was found to be the best solvent. In ¹⁹⁵Pt NMR, the complexes containing bidentate amines forming five-membered chelates were observed at higher fields than those containing monodentate amines. The resonances of the NH₃ compounds were also found at lower fields than the primary amine complexes. All the dicarboxylato ligands form six-membered chelates except 1,2-CBDCA, whose Pt(II) compounds were observed at lower fields than the others. The crystal structures of Pt(en)(1,1-CBDCA), Pt(Meen)(1,1-CBDCA) and Pt(en)(benzylmalonato) were confirmed by X-ray diffraction methods. Several compounds are disordered. The crystals are stabilized by intermolecular hydrogen bonds between the -NH₂ groups and the carboxylato O atoms.     

Homoleptic platinum(II) and palladium(II) complexes of 1,5,9-trithiacyclododecane: the crystal structures of [Pt(12S3)2](PF6)2 · 2CH3NO2 and [Pd(12S3)2](BF4)2 · 0.5H2O

The synthesis, spectroscopy, electrochemistry, and crystal structures of two new mononuclear homoleptic Pt(II) and Pd(II) complexes with the crown trithioether 1,5,9-trithiacyclododecane (12S3) are reported. In contrast to behavior with analogous smaller ring trithiacrowns, both metal complexes exhibit exodentate axial sulfur donors, a consequence of the preferred conformation of the 12S3 ligand. The lack of two axial metal-sulfur interactions correlates with the observed electronic spectroscopy and oxidative electrochemistry displayed by the complexes and contrasts with properties exhibited by complexes containing smaller polythioether macrocycles. The two complexes have electronic spectra dominated by charge transfer, not d-d bands and show no M²⁺/M³⁺ couples. Both complexes show a fluxional 12S3 ligand in solution due to a 1,5-metallotropic shift, an uncommon observation of this particular type of intramolecular ligand exchange. The ¹⁹⁵Pt NMR chemical shift of −4201 ppm for [Pt(12S3)₂]²⁺ is consistent with an alternating positioning of the four sulfur lone pairs on the coordinated thioethers. Although 12S3 is poorly pre-organized for facial complexation, its flexibility to position a sulfur in an exodentate fashion enables it to form stable complexes with d⁸ metal ions such as Pt(II) and Pd(II).     

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.     

Synthesis and characterization of new ternary Cu(II)-polyamines-ATP complexes

Four new complexes of Cu(II) of stoichiometry [Cu(ATP)(polyamine)] containing as ligands the polyamines (PA) ethylenediamine, 1,3-diaminopropane, spermidine or spermine and adenosine 5′triphosphate were prepared from aqueous solution at pH 6. The synthesis, characterization, thermogravimetric, vibrational spectroscopy, electron paramagnetic resonance analyses are described and show that these complexes have similar molecular structures. The infrared spectra and the thermal analysis are briefly discussed based on the peculiarities of the complexes. The IR spectra of the ligands and their copper complexes were used to assign the various groups and compare the shifts due to complexation. The EPR parameters values for the complexes show that Cu(II) is complexed in a similar way in the four complexes. Similarity in the coordination mode of complexes in solid state has been determined and discussed. The data obtained suggest that the four complexes present one water molecule of hydration and are complexed through two oxygen atoms from ATP and through two nitrogen atoms of each polyamine.     

Spectroscopic aspects of the coordination modes of 2,4-dithiohydantoins: Experimental and theoretical study on copper and nickel complexes of cyclohexanespiro-5-(2,4-dithiohydantoin)

The complexation of cyclohexanespiro-5-(2,4-dithiohydantoin), L, with copper and nickel was studied by means of experimental and theoretical methods. The Cu(I) and Ni(II) complexes were synthesized and characterized using ¹³C CPMAS NMR, IR and FAB-MS. Reduction of Cu(II) ions and the formation of Cu(I) complexes with dithiohydantoin was proved. Various coordination modes were investigated on the basis of calculated (DFT-GIAO) shielding constants of the free ligand and model structures of the complexes. General trends in the changes of spectroscopic parameters (NMR chemical shifts, vibrational modes) upon different types of coordination were outlined. Dimeric structures for the Cu(I) and Ni(II) complexes were proposed in which the ligands were coordinated in N3^S4- and N3^S2-bridging ways, respectively, acting as monoanions. The results demonstrate that the combined experimental (¹³C CPMAS NMR, IR) and theoretical (DFT) approach can be used to characterize the molecular structure of solid complexes for which crystallographic data are not available.     

Binding of mercury(II) to poly(dA-dT) studied by proton nuclear magnetic resonance

The binding of Hg(II) to poly(dA-dT) has been examined with proton NMR spectroscopy. Addition of HgCl2 between r (Hg2+/nucleotide) = 0 and 0.25 results in loss of the exchangeable imino N3H resonance of thymine, indicating preferential binding at this site. The nonexchangeable base resonances AH8, AH2, and TH6 shift their intensity downfield in a cooperative manner, indicating complexation which is slow on the NMR time scale and changes in the polymer conformation upon binding. At r = 0.25, the polymer is cross-linked, and an increase in temperature does not result in denaturation of the polymer, as evidenced by the thymine proton resonance chemical shifts. The chemical shifts of the AH2 and T(CH3)5 base resonances allow some general conclusions to be made about the stereochemistry of this complex.     

Study of Pt(II)-aromatic amines complexes of the types cis- and trans-Pt(amine)2I2, [Pt(amine)4]I2 and I(amine)Pt(μ-I)2Pt(amine)I

Pt(II) complexes of the types cis- and trans-Pt(amine)₂I₂ with amines containing a phenyl group were synthesized and studied mainly by IR and multinuclear (¹⁹⁵Pt, ¹H and ¹³C) magnetic resonance spectroscopies. The compounds are not very soluble. In ¹⁹⁵Pt NMR spectroscopy, the cis isomers were observed at slightly lower fields than the trans analogues (average Δδ = 11 ppm) in acetone. In ¹H NMR, the NH groups were also found at slightly lower fields in the cis isomers. The coupling constants ²J(¹⁹⁵Pt-¹HN) varied from 53 to 85 Hz and seem slightly smaller in the trans configuration. The ¹³C NMR spectra of most of the complexes were measured. No coupling constants J(¹⁹⁵Pt-¹³C) were detected due to the low solubility of the compounds. The cis isomers containing a phenyl group on the N atom could not be isolated except for Ph-NH₂ which was shown to be a mixture of isomers in acetone. The tetrasubstituted ionic compounds [Pt(amine)₄]I₂ for the less crowded ligands were also studied mainly by NMR spectroscopy in aqueous solution. The ¹⁹⁵Pt chemical shifts vary between −2855 and −2909 ppm. The coupling constants ³J(¹⁹⁵Pt-¹H) are about 40 Hz. The iodo-bridged dinuclear species I(amine)Pt(μ-I)₂Pt(amine)I were also synthesized and characterized. Two isomers are present in acetone solution for most of the compounds. Their δ(Pt) signals were observed at about −4000 ppm and their coupling constants ²J(¹⁹⁵Pt-¹HN) are around 69 Hz.     

Synthesis and characterization of the novel Pt(II) complexes of the types cis- and trans-Pt(Ypy)(pyrazine)Cl2, K2[Cl3Pt(μ-pyrazine)PtCl3] and trans, trans-(Ypy)Cl2Pt(μ-pyrazine)Pt(Ypy)Cl2 (Ypy = pyridine derivative)

New types of Pt(II) mixed-ligand complexes containing a pyridine derivative (Ypy) and pyrazine (pz) were synthesized. The compounds were characterized by infrared spectroscopy and by multinuclear (¹H, ¹³C and ¹⁹⁵Pt) magnetic resonance. The complexes cis-Pt(Ypy)(pz)Cl₂ were synthesized from the reaction of K[Pt(Ypy)Cl₃] with pyrazine (1:1 proportion) in water. When the reaction was carried on in a 2:1 ratio, a mixture of compounds was obtained, which was refluxed in CH₂Cl₂ for several days. The final product was found to be pure and it was identified as trans,trans-Cl₂(Ypy)Pt(μ-pyrazine)Pt(Ypy)Cl₂. The cis monomers isomerize to the trans isomers in organic solvents. Different methyl derivatives of pyridine were studied in order to determine the influence of substitution in ortho position on the pyridine ligand in the complexes. In IR spectroscopy, the cis monomers showed two ν(Pt-Cl) bands, while the trans monomers and dinuclear species showed only one ν(Pt-Cl) band. The NMR results were interpreted in relation to the solvent effect, which seems important in these complexes. The ¹⁹⁵Pt NMR signals of the cis monomers were found at slightly higher fields than those of the corresponding trans isomers. The coupling constants J(¹⁹⁵Pt-¹H) and J(¹⁹⁵Pt-¹³C) are larger in the cis geometry. The δ(¹⁹⁵Pt) of the dinuclear species were found close to those of the trans monomers and the coupling constants are similar to those of the trans monomers, strongly suggesting a trans-trans configuration for the dinuclear compounds. The pyrazine-bridged complex K₂[Cl₃Pt(μ-pz)PtCl₃] was also synthesized and spectroscopically studied. The crystal structures of the compounds cis-Pt(3,5-lut)(pz)Cl₂ and trans-Pt(2,4,6-col)(pz)Cl₂ were determined by X-ray diffraction methods.     

NMR studies on binary and ternary Pd(II) complexes formed by the growth-modulating tripeptide glycylhistidyllysine and nucleotides

The mechanism of transport of Pt(II) and Pd(II) into tissues through blood and that of their elimination in kidney is incompletely known so far. In this respect, the binding of palladium by the tripeptide glycyl-L-histidyl-L-lysine (GHL), a constituent of the human plasma, as a binary complex, and by the nucleotides 5'-IMP and 5'-GMP, as ternary complexes, has been studied by 1H and 13C NMR spectroscopy. These studies have been conducted in aqueous media and at different ligand/metal ratios. At acidic pH, resonances were observed for binary and ternary kinetically stable complexes, and binding sites in these complexes were identified by the effect of binding on chemical shifts of protons and carbon resonances. From these data, stoichiometries and structures of these complexes were proposed.