Kevin B. Nolan

Synthesis and characterisation of mercaptoimidazole, mercaptopyrimidine and mercaptopyridine complexes of platinum(II) and platinum(III). The crystal and molecular structures of tetra(2-mercaptobenzimidazole)- and tetra(2- mercaptoimidazole)platinum(II) chloride

Abstract Reaction of K2[PtCl4] with 2-mercaptobenzimidazole (HL2) and 2-mercaptoimidazole (HL3) in aqueous ethanol afforded the new, crystalline, square-planar platinum(II) complexes [Pt(HL2)4]Cl2.EtOH (4) and [Pt(HL3)4]Cl2.2H2O (5), the crystal and molecular structures of which are reported. In both complexes the ligands are present in the thione form with coordination taking place through the sulphur atom only. The Pt–S bond lengths are 2.304(4) and 2.312(3) A in complex (4) and 2.314(12) and 2.317(12) A in complex (5). The S–Pt–S bond angles are 90.33(13) and 89.67(13)° in complex (4) and 94.46(4) and 85.54(4)° in complex (5). Reaction of the ligands 4-hydroxy-2-mercaptopyrimidine (HL4) and 2-mercaptopyridine (HL5) with K2[PtCl4] gave the new, dimeric platinum(III) complex [Pt2(L4)4Cl2] (6) and [Pt2(L5)4Cl2]·EtOH (7) which is similar to a previously reported complex prepared by a different method. In these complexes the organic ligands are bridging N, S donors, the chlorides are terminally coordinated to each platinum and there is a platinum–platinum bond. The reaction of 4-amino-2-mercaptopyrimidine (HL6) with K2[PtCl4] gave the monomeric platinum(II) complex cis-[Pt(HL6)2Cl2]·2H2O (8) in which each HL6 ligand is coordinated to the metal ion via the exocyclic amino group. Reaction of 4,6-dihydroxy-2-methylmercaptopyrimidine (HL7) with K2[PtCl4] gave the dimeric platinum(II) complex of formula [Pt2(L7)2(HL7)2]Cl2 (9), which is suggested to contain bridging L7 and HL7 ligands.

Metal complexes of salicylhydroxamic acid (H2Sha), anthranilic hydroxamic acid and benzohydroxamic acid. Crystal and molecular structure of [Cu(phen)2(Cl)]Cl H2Sha, a model for a peroxidase-inhibitor complex.

Stability constants of iron(III), copper(II), nickel(II) and zinc(II) complexes of salicylhydroxamic acid (H2Sha), anthranilic hydroxamic acid (HAha) and benzohydroxamic acid (HBha) have been determined at 25.0 degrees C, I=0.2 mol dm(-3) KCl in aqueous solution. The complex stability order, iron(III) >> copper(II) > nickel(II) approximately = zinc(II) was observed whilst complexes of H2Sha were found to be more stable than those of the other two ligands. In the preparation of ternary metal ion complexes of these ligands and 1,10-phenanthroline (phen) the crystalline complex [Cu(phen)2(Cl)]Cl x H2Sha was obtained and its crystal structure determined. This complex is a model for hydroxamate-peroxidase inhibitor interactions.

Metal complexes of amino acids and peptides

This chapter deals with the most important results and observations published on various aspects of the metal complex formation with amino acids, peptides and related ligands during the past two-three years. The major sources of the references collected here are the Abstracts reported by the Web of Science Databases on the Internet but the title pages of the most common journals of inorganic, bioinorganic and coordination chemistry have also been surveyed.

Synthesis of trans-bis (glycinehydroxamato) platinum (II) hydrate tans-dichlorobis (glycylglycine) platinum (II) dihydrate and the crystal and molecular structures of trans-dichlorobis (glycine) platinum (II) dihydrate and trans, trans-dichlorobis (glycinato) platinum (IV), hydrolysis products formed in reactions of the former complexes

Abstract The complex trans -bis (glycinehydroxamato) platinum (II) hydrate, trans -Pt (GHA) 2 ·H 2 O, in which the ligand is coordinated to the metal through its amino and deprotonated hydroxamate nitrogen atoms, has been synthesised. Reaction of this with HCl in aqueous solution produced crystals of trans -dichlorobis(glycine) platinum(II) dihydrate, trans -PtCl 2 (glyOH) 2 ·2H 2 O, resulting from hydrolysis of the glycinehydroxamate ligand. The crystal and molecular structures show that the complex is square planar with the chloride ligands trans to each other, as are the glycine ligands which are N-coordinated. The PtCl and Pt bond distances are 2.283 and 2.037 a, respectively. Extensive intermolecular hydrogen bonding in the crystal gives rise to a layer structure and each water molecule is involved in three hydrogen bonds. The complex trans -dichlorobis (glycylglycine) platinum(II) dihydrate was also prepared but attempts to oxidise it with H 2 O 2 resulted in hydrolysis of the peptide ligand as well as oxidation, giving trans,trans -dichlorobis(glycinato) platinum(IV), trans,trans -PtCl 2 (glyO) 2 . The crystal and molecular structures of this complex, one of the very few known platinum(IV)-amino acid complexes, have also been determined. The complex is octahedral with both glycinates and chlorides bonded trans to one another. In the crystal there are two chemically identical but crystallographically distinct molecules each of which occupies a special position in the crystallographic inversion centre. The average bond distances in this complex are, PtCl 2.305 A, PtN 2.051 A and PtO 1.987 A. In the crystal there is e extensive intermolecular hydrogen bonding, each complex molecule hydrogen bonded to six others giving a sheet-like structure.

Monohydroxamic acids and bridging dihydroxamic acids as chelators to ruthenium(III) and as nitric oxide donors: syntheses, speciation studies and nitric oxide releasing investigation

The synthesis and spectroscopic characterisation of novel mononuclear Ru(III)(edta)(hydroxamato) complexes of general formula [Ru(H2edta)(monoha)] (where monoha = 3- or 4-NH2, 2-, 3- or 4-C1 and 3-Me-phenylhydroxamato), as well as the first example of a Ru(III)-N-aryl aromatic hydroxamate, [Ru(H2edta)(N-Me-bha)].H2O (N-Me-bha = N-methylbenzohydroxamato) are reported. Three dinuclear Ru(III) complexes with bridging dihydroxamato ligands of general formula [{Ru(H2edta)}2(mu-diha)] where diha = 2,6-pyridinedihydroxamato and 1,3- or 1,4-benzodihydroxamato, the first of their kind with Ru(III), are also described. The speciation of all of these systems (with the exception of the Ru-1,4-benzodihydroxamic acid and Ru-N-methylbenzohydroxamic systems) in aqueous solution was investigated. We previously proposed that nitrosyl abstraction from hydroxamic acids by Ru(III) involves initial formation of Ru(III)-hydroxamates. Yet, until now, no data on the rate of nitric oxide (NO) release from hydroxamic acids has been published. We now describe a UV-VIS spectroscopic study, where we monitored the decrease in the ligand-to-metal charge-transfer band of a series of Ru(III)-monohydroxamates with time, with a view to gaining an insight into the NO-releasing properties of hydroxamic acids.

Metal complexes of salicylhydroxamic acid and O-acetylsalicylhydroxamic acid

The salicylhydroxamic acid (H2Sha) complexes, Ni(HSha)2·2H2O, Cu(HSha)2·2H2O, Zn(HSha)2·1.5H2) and Fe(Sha)3·2H2O, in which the ligand is coordinated to the metal through the hydroxamate group have been synthesised. Acetylation of salicylhydroxamic acid with acetyl chloride in pyridine gave O-acetylsalicylhydroxamic acid (H2Sha-OAc) in which the hydroxamate oxygen is acetylated and from which the complexes Ni(HSha-OAc)2·H2O and Zn(Sha-OAc) were prepared. In the zinc complex the ligand is coordinated to the metal through the phenolate oxygen and the deprotonated nitrogen of the acetylhydroxamic group, the latter being an extremely rate type of coordination in the case of this metal ion. Attempted preparation of iron(III) and copper(II) complexes resulted in deacetylation of the ligand and the formation of salicylhydroxamate complexes.

Complex formation between transition metal ions and salicylglycine, a metabolite of aspirin

Ionization constants and complex formation constants of salicylglycine (1) in aqueous solution at 25-degrees-C and ionic strength 0.2 mol dm-3 KCl have been determined. The pK(a) values for the ligand are 3.44(1) and 8.24(4) and H-1 NMR studies show that there is no further ionization at higher pH as was previously suggested. In the case of copper(II) there is no evidence for complex formation below pH 4 and the main species in solution at pH>5 according to pH-metric and UV-vis spectrophotometric evidence in MLH-1 in which the ligand is bonded to the metal through the phenolate and carboxylate oxygen atoms and the deprotonated peptide nitrogen. The species ML also exists albeit in low concentrations. At pH>10 the formation of MLH-2 resulting from ionization of an equatorial aquo ligand is observed. In the case of nickel(II) and zinc(II) no complex formation occurs below pH 6 but above this pH the species ML and MLH-1, the latter involving deprotonation of an aquo ligand, are observed although at pH > ca 8 in the case of nickel(II) and pH > approximately 7.5 in the case of zinc(II) precipitation occurs.

Metal complexes of taurine. The first reported solution equilibrium studies for complex formation by taurine at physiological pH; the copper(II)-glycylglycinate-taurine and the copper(II)-glycylaspartate-taurine systems.

The first solution studies at physiological pH for the formation of metal complexes of taurine, +NH3CH2CH2S03-, one of the most abundant low molecular weight organic compounds in the animal kingdom, are reported. The complexes Cu(Gly-GlyH-1) (1) and [Cu(Gly-AspH-1)] (2) react with taurine to give the ternary complexes [Cu(Gly-GlyH-1)taurine]- (3) (log K=2.95+/-0.03, I=0.2M, T=25.0 degrees C) and [Cu(Gly-AspH-1)taurine]2- (4) (log K=2.68+/-0.02) in which taurine acts as an N-donor ligand, most likely monodentate, without involvement of the sulphonate group in coordination. The results of the pH-metric studies are confirmed by visible and EPR spectrophotometric studies. The taurine complexes are less stable than the analogous complexes of beta-alanine due to the decreased basicity of the amino group in the former ligand, and in the case of the Cu(Gly-GlyH-1) complexes due to involvement of the carboxylate group of beta-alanine in axial coordination.

Reactions of coordinated nitriles. Nucleophilic attack by amines on cis-dichlorobisbenzonitrileplatinum(II)

Abstract The reactions of cis -PtCl 2 (C 6 H 5 CN) 2 with primary amines, RNH 2 , in chloroform at 30 °C have been investigated spectrophotometrically. With n-C 3 H 7 NH 2 and n-C 4 H 9 NH 2 as attacking nucleophiles two distinct reaction steps were observed and the products of these were isolated in the case of the former amine. The product of the first reaction is the amidine complex trans-[PtCl(n-C 3 H 7 NH 2 ){C 6 H 5 C-(NHC 3 H 7 )NH} 2 ] + which, in the second reaction undergoes replacement of coordinated Cl − by amine. The kinetics of these reactions were studied with n-butylamine as reacting nucleophile. For the first reaction the observed rate law is of the form, rate = K 3 [complex][RNH 2 ] 2 , while the second reaction follows the expected second order kinetic behaviour. With diethylamine as attacking nucleophile only the first of these reactions was observed.

A convenient parallel synthesis of low molecular weight hydroxamic acids using polymer-supported 1-hydroxybenzotriazole

A convenient two-step procedure for the parallel synthesis of hydroxamic acids from carboxylic acids and hydroxylamine in good to high yields is reported. It involves the formation of a polymer-bound HOBt active ester and subsequent reaction with O-protected or free hydroxylamine. The hydroxamates are isolated with high purities by simple evaporation of volatile solvents. The use of free hydroxylamine leads to increased yields while maintaining high purities. Recycling of the spent resin to produce the same or a different hydroxamic acid has been achieved by a three-step protocol which is easily amenable to automation and cost-economical. The method presented here is well suited to the preparation of the title compounds and can be used effectively to synthesise large molecules containing a hydroxamic acid group.