Michele Gullotti

Synthesis, characterization and catalytic oxidations of oxovanadium(IV), oxotitanium(IV) and dioxomolybdenum(VI) complexes with chiral imines of L-amino acids

Abstract Representative oxovanadium(IV), oxotitanium(IV), and dioxomolybdenum(VI) complexes of N-salicylidene-L-amino acids (the amino acids are: valine, leucine, except for Mo(VI), and histidine) have been synthesized and characterized by various spectroscopic techniques. It has been found that while in the histidine complexes of titanium(IV) and vanadium(IV) the amino acid residue is bound in the expected glycine-like mode, in the molybdenum(VI) complex it is bound in the unusual histamine-like mode. Also, the structure of this molybdenum(VI) complex contains imidazolate-bridged polymeric units in the solid state, while the carboxyl group of the amino acid residue is protonated. In solution the polymeric structure is cleaved and the monomers contain carboxylate and protonated imidazole groups at the histidine residue. The histamine-like structure of the histidine complex was probcd by comparison with that of the chiral dioxomolybdenum(VI) complex of N -salicylidene-L-histidinol. While the structure of the metal centers is six-coordinate for the dioxomolybdenum(VI) complexes and the histidine complexes of oxotitanium(IV) and oxovanadium(IV), it is likely that the complexes of the latter metals derived from nonpolar amino acids do not achieve coordination numbers higher than five. The present oxometal complexes are catalytically active in the sulfoxidation of sulfides and in the epoxidations of activated olefins by tert-butyl hydroperoxide, but in general exhibit a low degree of asymmetric induction in these reactions.

Coordination modes of histidine: 4. Coordination structures in the copper(II)-L-histidine (1:2) system

The coordination structures of various species in the copper(II)-L-histidine (1:2) system in aqueous solution have been deduced by investigating the pH dependence of the electronic and circular dichroism spectra. The contribution to the spectra of the glycine-like and histamine-like binding modes of L-histidine has been determined by recording the spectra of the ternary system copper(II)-histamine-L-histidine (1:1:1) and copper(II)-amino acid-L-histidine (1:1:1), respectively, in neutral aqueous solutions. Apical binding to copper(II) by the donor atom on the histidine side chain can contribute significantly to the stabilization of each of the two basic histidine binding modes. It has been concluded that Cu(HL)2+ (L-histidine = HL), the major species below pH approximately 3, contains a glycine-like bound histidine ligand with an unbound imidazolium cation. The species Cu(HL)L+, which is prominent in the pH region near 4.5, contains a glycine-like bound histidine molecule, with protonated imidazole ring, and a histamine-like bound histidine molecule. CuL2, the major species at neutral pH, exists in solution as an equilibrium mixture of a mixed-type chelation structure, with a glycine-like and a histamine-like bound histidine ligand, and a structure containing both histidine ligands bound histamine-like. The species containing deprotonated imidazole nuclei, such as Cu(H-1L2)-, which predominates above pH approximately 11, show an increased contribution by structures containing glycine-like bound histidine compared with CuL2.

Biomimetic Oxidations by Dinuclear and Trinuclear Copper Complexes

Publisher Summary This chapter discusses biomimetic oxidations by dinuclear and trinuclear copper complexes. Copper is widely employed as metal cofactor in proteins and enzymes that perform dioxygen binding, activation, and reduction processes. The chapter also provides general overviews describing the catalytic reactions and structural features of the protein active sites. Copper proteins and enzymes can be classified into structural types, according to the nuclearity of their active sites, which can be mononuclear, binuclear, or polynuclear, but in general, protein function is not directly correlated with the nuclearity of the active site. For instance, mononuclear copper enzymes perform oxidase, monooxygenase, and dioxygenase activities. The best-known representative members of the former family of proteins are hemocyanin, catechol oxidase and tyrosinase, and those of the latter family are ascorbate oxidase, laccase, and ceruloplasmin. The basic properties of these proteins are the necessary reference for any attempt to reproduce in biomimetic systems key aspects of the protein structure and reactivity.

Schiff base complexes of oxocations—I Uranyl complexes with tetradentate optically active Schiff bases of salicylaldehyde

Abstract The synthesis and properties of uranyl complexes with tetradentate ligands of formula UO 2 (saldiamine). L (where saldiamine is the Schiff base N,N′diamine bis(salicylideneimine), L is a solvent molecule and the diamines are ethylenediamine, (+) propylenediamine, (+) and meso butanediamine, (+) and meso cyclohexanediamine, (−) and meso stilbenediamine) are reported. I.R., electronic and circular dichroism spectra are also discussed.

Binding of nitrite and its reductive activation to nitric oxide at biomimetic copper centers

Abstract The reactivity of nitrite towards the copper(II) and copper(I) centers of a series of complexes with tridentate nitrogen donor ligands has been investigated. The ligands are bis[(1-methylbenzimidazol-2-yl)methyl]amine (1-bb), bis[2-(1-methylbenzimidazol-2-yl)ethyl]amine (2-bb), and bis[2-(3,5-dimethyl-1-pyrazolyl)ethyl]amine (ddah) and carry two terminal benzimidazole (1-bb, 2-bb) or pyrazole (ddah) rings and a central amine donor residue. While 2-bb and ddah form two adjacent six-membered chelate rings on metal coordination, 1-bb forms two smaller rings of five members. The binding affinity of nitrite and azide to the Cu(II) complexes (ClO4− as counterion) has been determined in solution. The association constants for the two ligands are similar, but nitrite is a slightly stronger ligand than azide when it binds as a bidentate donor. The X-ray crystal structure of the nitrite complex [Cu(ddah)(NO2)]ClO4 (final R=0.056) has been determined: triclinic P1¯space group, a=8.200(2) Å, b=9.582(3) Å, c=15.541(4) Å. It may be described as a perchlorate salt of a “supramolecular” species resulting from the assembly of two complex cations and one sodium perchlorate unit. The copper stereochemistry in the complex is intermediate between SPY and TBP, and nitrite binds to Cu(II) asymmetrically, with Cu-O distances of 2.037(2) and 2.390(3) Å and a nearly planar CuO2N cycle. On standing, solutions of [Cu(ddah)(NO2)]ClO4 in methanol produce the dinuclear complex [Cu(ddah)(OMe)]2(ClO4)2, containing dibridging methoxy groups. In fact the crystal structure analysis (final R=0.083) showed that the crystals are built up by dinuclear cations, arranged on a crystallographic symmetry center, and perchlorate anions. Electrochemical analysis shows that binding of nitrite to the Cu(II) complexes of 2-bb and ddah shifts the reduction potential of the Cu(II)/Cu(I) couple towards negative values by about 0.3 V. The thermodynamic parameters of the Cu(II)/Cu(I) electron transfer have also been analyzed. The mechanism of reductive activation of nitrite to nitric oxide by the Cu(I) complexes of 1-bb, 2-bb, and ddah has been studied. The reaction requires two protons per molecule of nitrite and Cu(I). Kinetic experiments show that the reaction is first order in [Cu(I)] and [H+] and exhibits saturation behavior with respect to nitrite concentration. The kinetic data show that [Cu(2-bb)]+ is more efficient than [Cu(1-bb)]+ and [Cu(ddah)]+ in reducing nitrite.

Synthetic models for biological trinuclear copper clusters. Trinuclear and binuclear complexes derived from an octadentate tetraamine-tetrabenzimidazole ligand

The new tetraamino-tetrabenzimidazole ligand N,N ′{bis[3-(1-methyl-2-benzimidazolyl]amino}piperazine (L) has been synthesised together with a series of trinuclear and binuclear complexes. Two terminal binding sites with tridentate linkages (A sites) and one central binding site with the bidentate piperazine residue (B site) are used by the ligand to bind divalent metal centres in the trinuclear complexes [Cu H 3 L] 6+ , [Cu H 2 Zn H L] 6+ , and [Cu H 2 Co H L] 6+ . In the binuclear complex [Cu H 2 L] 4+ each nitrogen donor of the piperazine rine acts as an axial ligand for the two coppers bound to A sites, but these piperazine donors can be easily displaced by protonation to form the [Cu H 2 LH 2 )] 6+ species. The structure of this protonated complex has been determined by X-ray analysis. The crystals of composition [Cu H 2 (LH 2 )(CH 3 CN) 4 ][ClO 4 ] 6 ·2H 2 O·3CH 3 CN belong to the monoclinic system. space group P 2 1 /n with cell parametrs a = 10.661 (3), b = 23.014(3), c = 17.217(4)A, β = 96.58(2)°, Z = 2. The citation is arranged on a crystallographic symmetry centre, which is located at the middle of the protonated piperazine ring. The protonation at the piperazine N atoms is supported by the total charge of the cation and by the analysis of the difference Fourier map. The copper ions are five-coordinated, with ligation of the two benzimidazole residues and the tertiary N donor in the basal plane of a distorted square pyramid. Two CH 3 CN molecules, one at the basal, the other at the apical position, complete the coordination polyhedron. The centrosymmetric spacer, between the tertiary N atoms, deviates from the higher C 2h symmetry, so that the two approximately planar N (CH 2 ) 3 groupings lie in two parallel planes. Complexes containing reduced copper ions, [Cu H 2 L 2+ and [Cu H 2 Cu II L] 4+ , have also been obtained, but these ions do not bind to the piperazine B site which can only be used to coordinate divalent metal ions. The complexes containing Cu(II) centres exhibit EPR signals indicative of mononuclear species with tetragonal symmetry. The different coordination environment of [Cu H 2 L] 4+ with respect to [Cu H 2 Zn H L] 6+ , [Cu H 2 Co H L] 6+ or [Cu H 2 (LH 2 ] 6+ is reflected by a difference in the magnetic parameters of the complexes. The EPR spectrum of [Cu H 3 L] 6+ is very similar to those of [Cu H 2 Zn H L] 6+ , typical for Cu(II)-A sites, but the integrated intensity accounts for only about 2.2 paramagnetic centres per molecule. It is likely that a dipolar interaction between one of the Cu(II)-A centres and the Cu(II)-B centre produces severe broadening of the corersponding signals and apparent reduction in the overall EPR intensity. Voltammetric data in acetonitrile solution exhibit quasi-reversible electron transfer for the Cu(II)/Cu(II) couples with estimated reduction potentials in the range 0.39–0.56 V versus NHE. The voltammogram of [Cu H 3 L] 6+ run at low concentration and sweep rate shows that the three-electron transfer in split into one-electron and two-electron steps. Binding experiments show that the complexes bind azide molecules in the terminal mode to the copper (II) centres with affinity constants decreasing in the series: [Cu H 3 L] 6+ > [Cu H 2 L] 4+ . The complexes derived from L are catalytically active in the air oxidation of di-tert-butylcatechol (DTBC). The oxidations are biphasic, with a fast initial stoichiometric phae corresponding to reduction of a pair of copper(II) centres and oxidation of DTBC to quinone followed by the catalytic reaction. The catalytic reaction follows substrate saturation behaviour, with kinetic constants decreasing in the order: [Cu H 3 L 6+ > [Cu H 2 Co H L] 6+ > [Cu H 2 Zn H L] 6+ ≈ [Cu H 2 L] 4+ . Anaerobic experiments show that the two-electron oxidation of DTBC involves reduction of one Cu(II)-A site and the Cu(II)-B site for [Cu H 3 L] 6+ , both the Cu(II)-A sites of Cu H 2 Zn H L] 6+ and [Cu H 2 K] 4+ , but one Cu(II)-A and Co(III) in the case of the mixed [Cu H 2 Co 11 L] 6+ complex, since the Co(II) ion is rapidly oxidised to Co(III) in the conditions in which the catalytic reaction is carried out.

Enantiomeric cisplatin analogues: an investigation on their activity towards tumors in mice

Abstract A series of enantiomeric cisplatin analogues of formula [diamPtCl2] (diam = chiral chelating diamine) and the corresponding sulfato derivatives was prepared and tested for activity against tumors in mice, particularly P 388 leukemia. The configuration of the diamines has practically no influence on the antitumor activity. The effects of the leaving group and of the nature of the diamines are briefly discussed.

Copper(II)-N2S2 complexes of the imines of 1-phenyl-3-formyl-2(1H)-pyridinethione

Abstract Several copper(II) complexes of the imines formed by condensation of 1-phenyl-3-formyl-2(1 H )-pyridinethione and a primary amine (pyt-R) or a diamine (pyt 2 -R′) have been synthesized and characterized. The complexes have a CuN 2 S 2 core and the sulfur donors exhibit thiolate character. The complexes of type [Cu(pyt 2 -R′)] [ClO 4 ] 2 display optical and ESR spectral behavior that indicates a progressive distortion of the metal coordination geometry from square- planar toward flattened tetrahedral as the carbon chain length of the R′ bridge is varied from two to four atoms. The spectral properties of the complexes of type [Cu(pyt-R) 2 ] [ClO 4 ] 2 are more similar to one another and indicate significant distortion of Cu(II) from the planar arrangement.

Stereoselective catalytic oxidations of biomimetic copper complexes with a chiral trinucleating ligand derived from 1,1-binaphthalene

Abstract The new octadentate ligand R-(−)-N,N′-dimethyl-N,N′-bis{3-[bis(1-methyl-2-benzimidazolyl)amino]propyl}1,1′-binaphthalenyl-2,2′-diamine (L) was employed for the synthesis of dinuclear and trinuclear copper(II) complexes. Two terminal binding sites with tridentate aminobis(benzimidazole) linkages (A sites) and one central binding site with the bidentate diamino-binaphthalenyl residue (B site) are used by the ligand to bind divalent metal centres in the trinuclear complex [Cu3L][ClO4]6. Spectroscopic measurements suggest that in the dinuclear complex [Cu2L][ClO4]4 the copper ions are five-coordinated, with ligation by the aminobis(benzimidazole) residues, one of the tertiary amine donors of the diamino-binaphthalenyl moiety, and one water molecule. The complexes bind azide in the μ-1,3 fashion at low concentration and in the terminal mode at high concentration. The copper(II) complexes derived from L are catalytically active in the oxidation of 3,5-di-tert-butylcatechol (DTBC) by dioxygen. The oxidations are biphasic, with a fast initial stoichiometric phase corresponding to reduction of a pair of copper(II) centres and oxidation of DTBC to quinone, followed by the catalytic reaction, that follows substrate saturation behaviour. The complexes act as stereoselective catalysts in the biomimetic oxidations of the optically active catechol derivatives l - and d -Dopa and their methyl esters. In all the cases, the preferred enantiomeric substrate has the L configuration. This preference is dictated by the chirality of the binaphthalenyl residue.

A new chiral, poly-imidazole N8-ligand and the related di- and tri-copper(II) complexes: synthesis, theoretical modelling, spectroscopic properties, and biomimetic stereoselective oxidations

The new poly-imidazole N(8) ligand (S)-2-piperazinemethanamine-1,4-bis[2-((N-(1-acetoxy-3-(1-methyl-1H-imidazol-4-yl))-2-(S)-propyl)-(N-(1-methyl-1H-imidazol-2-ylmethyl)))ethyl]-N-(phenylmethyl)-N-(acetoxy), also named (S)-Pz-(C2-(HisIm))(2) (L), containing three chiral (S) centers, was obtained by a multi-step synthesis and used to prepare dinuclear [Cu(2)(L)](4+) and trinuclear [Cu(3)(L)](6+) copper(II) complexes. Low-temperature EPR experiments performed on [Cu(2)(L)](4+) demonstrated that the two S = ½ centers behaved as independent paramagnetic units, while the EPR spectra used to study the trinuclear copper complex, [Cu(3)(L)](6+), were consistent with a weakly coupled three-spin ½ system. Theoretical models for the two complexes were obtained by DFT/RI-BP86/TZVP geometry optimization, where the structural and electronic characteristics nicely supported the EPR experimental findings. In addition, the theoretical analysis unveiled that the conformational flexibility encoded in both [Cu(2)(L)](4+) and [Cu(3)(L)](6+) arises not only from the presence of several σ-bonds and the bulky residues attached to the (S)-Pz-(C2-(HisIm))(2) ligand scaffold, but also from the poor coordination ability of the tertiary amino groups located in the ligand side-chains containing the imidazole units towards the copper(II) ions. Both the dinuclear and trinuclear complexes are efficient catalysts in the stereoselective oxidation of several catechols and flavonoid compounds, yielding the corresponding quinones. The structural features of the substrate-catalyst adduct intermediates were assessed by searching the conformational space of the molecule through MMFF94/Monte Carlo (MMFF94/MC) methods. The conformational flexibility of the bound ligand in the complexes proves to be beneficial for substrate binding and recognition. For the dinuclear complex, chiral recognition of the optically active substrates derives from weak electrostatic interactions between bound substrates and folded regions of the ligand scaffold. For the trinuclear complex, in the case of L/D-Dopa, the chiral recognition has a remarkable stereoselectivity index of 75%, the highest so far reported for this type of reaction. Here the dominant contribution to stereoselectivity arises from the direct interaction between a donor group (the Dopa carboxylate) far from the substrate reaction site (the catechol ring) with the additional (third) copper center not involved in the oxidative catalysis. On the other hand, in the case of bulky substrates, such as L/D-catechin, the observed poor substrate recognition is associated with much weaker interactions between the chiral regions of the complex and the chiral part of the substrate.