Jean-Pierre Laussac

Complete displacement of N,O bound amino acids (amacH) in cis-[(NH3)2Pt(amac)]NO3 chelates by 9-methylguanine (9-MeGH) and 9-methyladenine (9-MeA). The crystal structure of cis-[(NH3)2Pt(9-MeA-N7)2](NO3)2•1.5H2O

Abstract The reactions of the complexes cis-[(NH3)2Pt(amac)]NO3, where amac are glycine (gly), L-alanine (L- ala) and 2-aminobutyric acid (2-aba), chelated to Pt(II), with 9-methylguanine (9-MeGH) and 9- methyladenine (9-MeA) were studied in neutral and acidic aqueous solutions. Complete displacement of the amino acids resulted in the formation of the compounds cis-[(NH3)2Pt(9-MeGH)2](NO3)2 in neutral and cis-[(NH3)2Pt(9-MeA)2](NO3)2 in strongly acidic media. The latter compound contained two 9-MeA molecules, both coordinated through N(7). Its crystal structure was solved with X-ray diffraction techniques. Crystal data: space group C2/c, a = 18.506(2), b = 15.770(2), c = 16.422(2) A, β = 108.38(2)°, V = 4548(2) A3, Z = 8, R = 0.022 for 4447 independent reflections. The results are compared with other analogous cis-[(NH3)2Pt(purine derivative)2]2+ structures and discussed in terms of a possible cross-link between two N(7) sites of adjacent adenines in DNA.

trans-ternary complexes of Pd(II) with nucleosides and dipeptides. Models for trans-DDP-DNA-protein crosslinks

The reactions of complexes of the type trans-[Pd(dipeptide)2Cl2] with the nucleosides guo and ino in aqueous solutions, produce the ternary complexes trans-[Pd(dipeptide)2(nucl)2]Cl2, which were isolated and characterized as solid adducts, with elemental analysis, conductivity measurements, IR and 1H NMR spectra. Many isomers, corresponding to the head to head, head to tail and tail to tail orientations of the nucleosides, with two major ones called ‘closed’ and ‘opened’ forms, are observed with 1H NMR in D2O solutions, for the complexes. The ratio of the two major isomers being 1:1.5 in D2O solutions of the ‘opened’ to ‘losed’ form, favors the ‘opened’ form in DMSO-d6 solutions changing from 1:6 to 1:10 for the guo derivatives, while this form is the only one observed in the ino derivatives. Possible ligand-ligand interactions are detected in the 1H NMR spectra of the compounds. The anti conformation of the sugar moiety of guo is found to increase in the trans-ternary complexes of the present system and with the presence of the dipeptide, indicating that the model DNA-Pt-protein crosslink may be responsible for the toxicity of platinum drugs.

TETRA-, PENTA- AND HEXACOORDINATED ALUMINIUM: NMR AND X-RAY DIFFRACTION STUDIES OF THE COMPLEXES OF ETHYLENEDIAMINE WITH ALUMINIUM ISOPROPOXIDE AND ITS FLUORO ANALOGUES

Abstract The products resulting from the complexation of Al[OCH(CH3)2]3 (A) and Al[OCH(CF2)3], with ethylenediamine have been studied. Four complexes en. Al[OCH(CH3)2]3 (B); en.Al[OCH(CF3)2]3 (D); [en]2. Al[OCH(CF3)2]3 (E) and en. Al(OH)[OCH(CF3)2]3 (F) were isolated and identified by elemental analysis and NMR spectroscopy. The occurence of a further complex (C) en. 2Al[OCH(CH3)2]3 in solution is suggested by the NMR data. A crystal structure determination is reported for the species (F). The structure consists of en.Al(OH)[OCH(CF3)2]2 dimers with characteristic (N2O4) ligand donor sets. The Al-Al distance (2.939 A indicates that no metal-metal interaction occurs. For the other complexes, the NMR, and in particular the 27Al NMR, data are shown to be consistent with a tetracoordinated aluminium atom in an (O3N) environment (compounds B and D) or with a penta-coordinated aluminium in an (O4 N) environment (C) or in an (O3 N2) environment (E).

Use of cyclic peptides to mimic the active sites of metalloproteins: 13C and 1H NMR, ESR and visible spectra of copper(II) complexes with the cyclo(GlyHisGlyHisGlyHisGly) peptide in aqueous solution

Abstract Cyclic peptides have been used to model various aspects of protein conformation and active sites [1]. In such models the usual flexibility of peptide chains is substantially reduced through cyclization. Furthermore, it is generally assumed that specific amino acid residues such as Glu, Asp, His, Lys⋯ have side chains that can bind to transition-metal ions. We chose to synthesize cyclo-(GlyHisGlyHisGlyHisGly) (hereinafter denoted (G 4 H 3 )) because the histidine residue plays an important role in metal ion coordination of metalloproteins and frequently encountered in vivo . Complexation of (G 4 H 3 ) with the transition metal ion Cu(II) in aqueous solution over a wide pH range and with different peptide/ metal ratios has been studied using carbon-13 and proton NMR, ESR and visible spectroscopy. From analyses of the spectral data, it is concluded that Cu(II) binds at two metal-binding sites depending on the pH. At physiological pH, the binding of Cu(II) at the first site involves the three HisN(3) imidazole groups to give a 1:1 species in a tetracoordinated structure; whereas, at higher pH, the binding of Cu(II) at the second site uses four deprotonated peptide nitrogens. The present results further confirm the concept of molecular design and the feasibility of designing peptide molecules mimicking the complicated metal-binding sites of biological macromolecules.

Structural and conformational analysis of metal-containing peptides by one- and two-dimensional NMR spectroscopy : the case of thymulin

Thymulin (formerly called FTS) is a well-defined nonapeptide hormone produced by thymic epithelial cells. Its biological activity and antigenicity depend on the presence of the metal zinc in the molecule. The interaction between this metal ion and thymulin has been investigated by means of one- and two-dimensional NMR experiments. These experiments were performed in dimethyl-d6 sulfoxide solution and in aqueous medium with different metal:peptide ratios. The results are compared with those obtained for complexes of thymulin with other metal ions (Cu2+ and Al3+) and for the [Ala4]- and [Ala8]-analogs in terms of biological activity. These comparative studies suggest that the 1:1 complex is the only conformation recognized by the antibodies. From the NOESY data, a spatial conformation has been proposed for this complex. This conformation should be the physiological one and could lead to a better insight into the conformation requirements at receptor sites.