Evy Manessi-Zoupa

Insights into the role of zinc(II) sites in hydrolytic enzymes: study of the ZnII/X/(py)2CO (X=Cl−, N3−, SO42−; ) reaction systems

Abstract A bioinorganic model approach for the investigation of substrate activation by zinc active sites in hydrolytic enzymes has been initiated. Several reaction schemes involving the substrate analogue di-2-pyridyl ketone, (py)2CO, and Zn(II) sources afforded the new complexes [ ZnCl 2 {( py ) 2 CO }]( 1 ) , [ ZnCl 2 {( py ) 2 C ( OMe )( OH )}]( 2 ) , [ Zn 2 Cl 2 {( py ) 2 C ( OMe ) O } 2 ]( 3 ) , [ Zn 2 ( N 3 ) 2 {( py ) 2 C ( OMe ) O } 2 ]( 4 ) and [ Zn 2 ( SO 4 ) 2 {( py ) 2 C ( OMe )( OH )} 2 ( MeOH ) 2 ]( 5 ) , which have been characterized by single-crystal X-ray crystallography and spectroscopic techniques. The chemical and structural identity of the products depends on the solvent, the hydroxide concentration and the nature of the inorganic anion. The biological relevance of the prepared complexes is also discussed.

Reactions of 3d-metal nitrates with N,N′-bis(2-pyridyl)urea (LH2): preparation, X-ray crystal structures and spectroscopic studies of the products trans-[M(II)(ONO2)2(LH2)2] (M=Mn, Fe, Co, Ni, Cu, Zn) and mer-[Co(III)(LH)2](NO3)·MeOH

Abstract The reactions of M(NO 3 ) 2 ·4H 2 O (M=Mn, Zn), M(NO 3 ) 2 ·6H 2 O (M=Co, Ni), Cu(NO 3 ) 2 ·3H 2 O and Fe(NO 3 ) 3 ·9H 2 O with the di-substituted urea ligand N , N ′-bis(2-pyridyl)urea (LH 2 ) were studied in methanol. The new complexes trans -[M(II)(ONO 2 ) 2 (LH 2 ) 2 ], where M=Mn ( 1 ), Fe ( 2 ), Co ( 4 ), Ni ( 6 ), Cu ( 7 ) and Zn ( 8 ), mer -[Co(III)(LH) 2 ](NO 3 )·MeOH ( 5 ) and [Fe 2 (III,III)O(NO 3 ) 4 (LH 2 ) 2 (MeOH) 2 ] ( 3 ) have been isolated. Of remarkable chemical interest is the reduction of iron(III) under aerobic conditions to give complex 2 and the presence of the deprotonated ligands in the cobalt(III) complex 5 . Complexes 1 , 2 and 4 – 8 have been structurally characterised by single-crystal X-ray studies. The structures of 1 , 2 , 4 and 6 – 8 consist of centrosymmetric octahedral molecules; the ligand LH 2 behaves as a bidentate chelate with the ligated atoms being the urea (amide) oxygen and one of the 2-pyridyl nitrogens, while the coordination sphere of the metal ion is completed by two monodentate nitrato groups. The coordination geometry around low-spin Co(III) in 5 is distorted octahedral; LH − chelates as a tridentate through both pyridyl nitrogen atoms and the deprotonated urea nitrogen atom forming one six- and one four-membered chelate ring. The new complexes were characterised by elemental analyses, thermal decomposition data, magnetic susceptibilities at room temperature and spectroscopic (IR, far-IR, Raman, UV–Vis, 57 Fe-Mossbauer, 1 H NMR) techniques. An oxo-bridged dinuclear structure with six-coordinate Fe(III) atoms is proposed for 3 . All data are discussed in terms of the nature of bonding and known or assigned structures.

Diorganotin(IV) complexes of dipeptides containing the α-aminoisobutyryl residue (Aib): Preparation, structural characterization, antibacterial and antiproliferative activities of [(n-Bu)2Sn(H−1L)] (LH = H-Aib-L-Leu-OH, H-Aib-L-Ala-OH)

Two new organotin(IV) complexes with dianionic dipeptides containing the alpha-aminoisobutyryl residue (Aib) as ligands are described. The solid complexes [(n-Bu)(2)Sn(H(-1)L(A))] x 2MeOH (1 x 2MeOH) (L(A)H=H-Aib-L-Leu-OH) and [(n-Bu)(2)Sn(H(-1)L(B))] x MeOH (2 x MeOH) (L(B)H=H-Aib-L-Ala-OH) have been isolated and characterized by single-crystal X-ray crystallography and spectroscopic techniques (H(-1)L(2-) is the dianionic form of the corresponding dipeptide). Complexes 1 x 2MeOH and 2 x MeOH are monomeric with similar molecular structures. The doubly deprotonated dipeptide behaves as a N(amino), N(peptide), O(carboxylate) ligand and binds to the Sn(IV) atom. The five-coordinate metal ion has a distorted trigonal bipyramidal geometry. A different network of intermolecular hydrogen bonds in each compound results in very dissimilar supramolecular features. The IR, far-IR, Raman and (119)Sn NMR data are discussed in terms of the nature of bonding and known structures. The antibacterial and antiproliferative activities as well as the effect of the new compounds on pDNA were examined. Complexes 1 and 2 are active against the gram-positive bacteria Bacillus subtilis and Bacillus cereus. The IC(50) values reveal that the two compounds express promising cytotoxic activity in vitro against a series of cell lines.

Structural features of angiotensin-I converting enzyme catalytic sites: conformational studies in solution, homology models and comparison with other zinc metallopeptidases.

Angiotensin-I Converting Enzyme (ACE) is a Zinc Metallopeptidase of which the three-dimensional structure was unknown until recently, when the X-ray structure of testis isoform (C-terminal domain of somatic) was determined. ACE plays an important role in the regulation of blood pressure due to its action in the frame of the Renin-Angiotensin System. Efforts for the specific inhibition of the catalytic function of this enzyme have been made on the basis of the X-ray structures of other enzymes with analogous efficacy in the hydrolytic cleavage of peptide substrate terminal fragments. Angiotensin-I Converting Enzyme bears the sequence and topology characteristics of the well-known gluzincins, a sub-family of zincins metallopeptidases and these similarities are exploited in order to reveal common structural elements among these enzymes. 3D homology models are also built using the X-ray structure of Thermolysin as template and peptide models that represent the amino acid sequence of the ACEs two catalytic, zinc-containing sites are designed and synthesized. Conformational analysis of the zinc-free and zinc-bound peptides through high resolution 1H NMR Spectroscopy provides new insights into the solution structure of ACE catalytic centers. Structural properties of these peptides could provide valuable information towards the design and preparation of new potent ACE inhibitors.

Transition metal complexes of N-(2-benzamide)pyridine-2′-carboxamide, a potentially tridentate ligand containing one secondary and one primary amide group: Preparation and characterization in the solid state

Abstract The synthesis of N-(2-benzamide)pyridine-2′-carboxamide (LH 2 ) is reported along with its employment as a ligand. The new complexes [MCl 2 (LH 2 ) 2 ]·DMF (M = Co, Ni), [Cu 2 Cl 4 (LH 2 ) 2 ]·DMF, [CuCl 2 (LH 2 ) 2 ], [Co(OH)(LH)] n ·nH 2 O, [M 2 (OH) 2 (H 2 O) x (LH) 2 ](M = Ni, Cu; x = 4,2), [M(LH) 2 ]·×H 2 O (M = Ni, Cu; x = 0, 1), [Ni(H 2 O) 2 (LH) 2 ]·H 2 O, and H 2 O, and [CuCl(LH)] n , where DMF = N,N-dimethylformamide, have been isolated. The complexes were characterized by elemental analyses, conductivity measurements, x-ray powder patterns, thermal methods, variable-temperature magnetic susceptibilities, and spectroscopic (IR and far-IR, ligand field, ESR) studies. A variety of stereochemistries is assigned for the complexes in the solid state. The neutral ligand acts as a bidentate chelating agent with ligated atoms being the ring nitrogen and the secondary amide oxygen; the LH − ion behaves as a bidentate chelating N ring , N secondary amide or as a tridentate N ring , N secondary amide , O primary amide ligand depending mainly on the reaction conditions.

New metal-binding modes for 5-aminoorotic acid: preparation, characterization and crystal structures of zinc(II) complexes

Treatment of ZnCl2 with 2 equivalents of 5-aminoorotic acid (5-amino-2,6-dioxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acid, H4L) and 2 equivalents of NaOH in water–methanol yielded a mixture of crystals and powder of complexes [{Zn(H2L)(H2O)2}n] 1 and [Zn(H3L)2(H2O)4] 2, respectively. A good yield (ca. 70%) of pure 2 can be obtained by the reaction of Zn(O2CMe)2·2H2O and 2 equivalents of H4L in refluxing water. The crystal structure of 1 consists of neutral octahedral [Zn(H2L)(H2O)2] units which form polymer chains along the b axis; H2L2– behaves as a bis(bidentate) bridging ligand co-ordinating to two zinc atoms via the amino nitrogen, the oxygen of the neutral carboxamide group, the deprotonated carboxamide nitrogen and one of the carboxylate oxygens and forming two five-membered chelate rings. The 1H NMR spectra of 1 in (CD3)2SO at 290 and 310 K suggest that its solid-state structure is not retained in solution. Slow crystallization of 1 or 2 from dmso solutions yielded crystals of the monomeric octahedral complex [Zn(H3L)2(dmso)2(H2O)2] 3 the structure of which was solved by single-crystal X-ray crystallography. The monoanion H3L– utilizes only one carboxylate oxygen for metal binding in the centrosymmetric complex 3. The difference in anionic charge and co-ordination mode between H2L2– and H3L– leads to different hydrogen-bonded supramolecular structures for 1 and 3. The IR and 1H NMR spectra of the prepared complexes are discussed.

Investigation of the Zinc Chloride / Methyl(2-pyridyl)ketone Oxime Reaction System: A Mononuclear Complex and an Inverse 12-Metallacrown-4 Cluster

The reactions of methyl(2-pyridyl)ketone oxime, (py)C(Me)NOH, with zinc chloride have been investigated. An excess of the ligand in EtOH/MeCN affords the mononuclear complex [ZnCl2{(py)C(Me)NOH}2] (1) in moderate yield. The metal ion is coordinated by two chloro ligands and two N,N′- chelating (py)C(Me)NOH molecules. The six-coordinate molecule is the ciscis- trans isomer considering the positions of the coordinated chlorine, pyridyl and oxime nitrogen atoms, respectively. The reaction between equimolar quantities of ZnCl2, (py)C(Me)NOH and LiOH·H2O in EtOH/MeCN leads to the tetranuclear cluster [Zn4(OH)2Cl2{(py)C(Me)NO}4] (2) in high yield. The molecule lies on a crystallographic inversion center and has an inverse 12-metallacrown- 4 topology. Two triply bridging hydroxides are accommodated within the metallacrown ring. Each (py)C(Me)NO− ligand adopts the 2.111 coordination mode (Harris notation), chelating one ZnII ion and bridging a ZnII 2 pair. Two metal ions are in a distorted O2N4 octahedral environment, whereas the other two are in a severely distorted tetrahedral O3Cl environment. Complex 2 joins a small family of structurally characterized zinc(II) metallacrown complexes. The IR data are discussed in terms of the nature of bonding and the structures of the two complexes.

THE INFRARED SPECTRA OF COMPLEXES WITH PLANAR DITHIOOXAMIDES. PART VIII. THE AU(III) COMPLEXES

Abstract In acid media Au(III) forms complexes with dithiooxamide (DTO) of formula [Au(DTO)(DTO)-H]Cl 2 and with N , N ′-dimethyldithiooxamide (DMDTO) of formula [Au(DMDTO-H) 1 X 2 ] (X is Cl or Br) and [Au(DMDTO) 1 Br 2 ]Br. In strong alkaline media for the N , N ′-disubstituted dithiooxamides a new type of complex could be obtained with formula A[Au(L) 2 ] (A is Li, Na or K; LH 2 is DMDTO or N , N ′-diethyldithiooxamide (DEDTO)). Infrared and Raman spectroscopy has been used to study of these complexes and also some thermal analysis is included. A thorough analysis of the vibrational spectra is carried out to reveal the structure of these complexes. From this it is concluded that all complexes have a square-planar geometry around Au(III) and that in all cases the dithiooxamides act as bidentate ligands coordinating through both sulphur atoms forming chelate ring systems. For the complexes formed in acid media special attention is given to the effect of hydrogen bonding on the infrared spectra, while for the complexes obtained in alkaline media the influence of the alkali counter-ion is investigated. From the TG data it is concluded that the forces in the ionic lattice of the A[Au(L) 2 ] complexes follow the series Li > Na > K.

Use of the 2-Pyridinealdoxime/N,N′-Donor Ligand Combination in Cobalt(III) Chemistry: Synthesis and Characterization of Two Cationic Mononuclear Cobalt(III) Complexes

The use of 2-pyridinealdoxime (paoH)/N,N′-donor ligand (L-L) “blend” in cobalt chemistry has afforded two cationic mononuclear cobalt(III) complexes of the general type [Co(pao)2(L-L)]+, where L-L = 1,10-phenanthroline (phen) and 2,2′-bipyridine (bpy). The CoCl2/paoH/L-L (1 : 2 : 1) reaction system in MeOH gives complexes [CoIII(pao)2(phen)]Cl·2H2O (1·2H2O) and [CoIII(pao)2(bpy)]Cl·1.5MeOH (2·1.5MeOH). The structures of the complexes were determined by single-crystal X-ray crystallography. The CoIII ions are six-coordinate, surrounded by three bidentate chelating ligands, that is, two pao− and one phen or bpy. The deprotonated oxygen atom of the pao− ligand remains uncoordinated and participates in hydrogen bonding with the solvate molecules. IR data of the complexes are discussed in terms of the nature of bonding and the known structures.

Preparation and characterization of trans- [Ni(ONO2)2(LH2)2]: The first structural determination of a complex containing the new ligand N,N′-bis(2-pyridyl)urea (LH2)

Abstract The complex trans -[Ni(ONO 2 ) 2 (LH 2 ) 2 ], where LH 2 is the new ligand N,N′-bis(2-pyridyl)urea derived unexpectedly from nicotinic or isonicotinic acid and 2-aminopyridine, was isolated. The ligand and its complex have been characterized by a variety of physical and spectroscopic techniques. The crystal structure of the complex reveals that LH 2 behaves as a bidentate chelate with ligated atoms being the amide oxygen and one of the pyridyl nitrogens.