Andrew M. Brodie

Antitumour copper(II) salicylaldehyde benzoylhydrazone (H2sb) complexes: physicochemical properties and the single-crystal X-ray structures of [{Cu(H2sb)(CCl3CO2)2}2] and [{Cu(Hsb) (ClO4) (C2H5OH)}2] and the related salicylaldehyde acetylhydrazone (H2sa) complex, [Cu(Hsa)Cl(H2O)]·h2O

Copper(II) complexes of the antitumour ligand salicylaldehyde benzoylhydrazone (H2sb) have been prepared. In the presence of strong acids, complexes of the neutral ligand were isolated: [{Cu(H2sb)X2}2]·nH2O (X = Br, n X = CCl3CO2, n = 0) and [Cu(H2sb)Cl2(H2O)]. In weakly acid or neutral media, monoanionic compounds separated: Cu(HsB)X2·nH2O] (X = Cl,Br, NO3, 0.3SO4, n = 0; X = ClO4, n = 1). With base only the highly insoluble dianionic complex [{Cu(sb)}2] was isolated. Also prepared was the related anionic ligand complex [Cu(Hsa)Cl(H2O)]·H2O (H2sa = salicylaldehyde acetylhydrazone). The complexes have been characterised by a range of physicochemical techniques and the crystal and molecular structures of [{Cu(H2sb)(CCl3CO2)2}2], [{Cu(Hsb)ClO4(C2H5OH)}2] and [Cu(Hsa)Cl(H2O)]·H2O, determined by single-crystal X-ray diffraction studies. Crystals [{Cu(H2sb)(CCl3CO2)2}2] are triclinic, space group , with = 10.130(2), b = 11.660(2), c = 11.876(2)r α = 67.07(2), β = 109-09(2)γ = 107.84(2)° and Z = 2. The complex is a centrosymmetric dimer, the monomeric units being bridged through the phenol oxygen. The copper coordination is tetragonal with the equatorial donor atoms coming from the tridentate ‘ONO’ donor ligand and the symmetry-related phenol oxygen. The more weakly bound axial donor oxygens are from the coordinated trichloroacetates. Crystals of [Cu(Hsb)ClO4(C2H5OH)2] are monoclinic, space group P21/c, with a = 11.2281(8), b = 7.9129(4), c = 21.043(1) ;rA β = 98.560(6)°✓ and Z = 4. This complex is also a centrosymmetric dimer, the monomeric units being bridged through the phenoxy oxygen. The copper coordination is tetragonal with the equatorial donor atoms coming from the tridentate ‘ONO’ ligand and the symmetry related phenoxy oxygen. The more weakly bound axial donor oxygens are supplied by the ethanol and perchlorato moieties. Crystals of [Cu(Hsa)Cl(H2O)]·H2O are monoclinic, space group P21/c, with . The complex is monomeric with the copper(II) adopting a square-pyramidal coordination. The four in-plane donors are provided by the tridentate ‘ONO’ donor Hsa and an oxygen from a coordinated water molecule; the axial site is occupied by the chloride ion. Most of the complexes have low magnetic moments and are assigned dimeric side-by-side structures. Powder ESR spectra have g1 and g✓ resolved often with ΔM = 2 transitions present.

The characterization of both the coordinated and non-coordinated saccharinate ion. The syntheses and crystal structures of aqua(2-formylpyridine thiosemicarbazonato)(saccharinato-N)copper(II) hemihydrate and 2,2'-bipyridyl-(2-formylpyridine thiosemicarbazonato)copper(II)saccharinate dihydrate

Abstract The preparation of the complex [CuL(sacc)- (H2O)]·0.5H2O (HL=2-formylpyridine thiosemicarbazone, Hsacc = saccharin) from the reaction of Na(sacc) with [{CuL(CH3COO)}2] is described. The complex [CuL(bpy)](sacc)·2H2O (bpy = 2,2′- bipyridyl) is obtained if the reaction is carried out in the presence of 2,2′-bipyridyl. The complexes have been characterized by a variety of physicochemical techniques and their crystal and molecular structures determined. Crystals of [CuL(sacc)(H2O)]·0.5H2O are monoclinic, space group P21/n, with a = 7.465(7), b = 9.245(7), c = 26.209(33) A, β = 97.18(9)° and Z = 4. Crystals of [CuL(bpy)](sacc)·2H2O are triclinic, space group P 1 , a = 9.243(1), b = 12.393(1), c = 13.323(1) A, α = 75.511(5), β = 67.751(5), λ = 73.294(7)° and Z = 2. Both complexes contain five coordinate copper with three donor atoms (NNS) contributed by L, which forms a tricyclic ligating system. For [CuL(sacc)(H2O)]·0.5H2O the coordination sphere is completed by a monodentate N-bound saccharinate ion and a more weakly bound water molecule giving a distorted square-pyramidal geometry. For the complex [CuL(bpy)](sacc)-2H2O the remaining coordination sites are occupied by two N atoms from 2,2′-bipyridyl, resulting in a geometry intermediate between square-pyramidal and trigonal- bipyramidal. The saccharinate ion is a non- coordinated anion.

Hexafluorosilicate coordination to the antitumour copper(II) salicylaldehyde benzoylhydrazone (H2L) system: single-crystal X-ray structure of [{Cu(HL)H2O}2SiF6]·2H2O

The complex [{Cu(HL)H2O}2SiF6]·2H2O (H2L = salicylaldehyde benzoylhydrazone) has been prepared from the reaction of CuF2·2H2O in concentrated HF with ethanolic solution of H2L. SiF62− was generated by the in situ reaction of fluoride on silica. The complex has been characterized by a range of physicochemical techniques and the crystal and molecular structure determined by single-crystal X-ray diffraction. The crystals of [{Cu(HL)H2O}2SiF6]·2H2O are monocliic, space group C2/c, with a = 13.677(5), b = 11.876(3), c = 20.3 A, β = 105.92(3)° and Z = 4. The complex is a discrete centrosymmetric dimer, the monomeric units being bridged by the coordinated SiF6 2− anion with the Si lying on the inversion centre. The copper atom has a distorted square-pyramidal geometry with three donor atoms (ONO) from the tridentate monoanionic HL− ligand and the fourth in-plane donor (O), from a water molecule. The fifth position is occupied by a less strongly bound fluorine from the bridging SiF62− anion. Alternate stacking of the dimeric units which would allow overlap of π electron density as well as H bonding involving all of the hexafluorosilicato F atoms appears to be important for the stability of the complex in the solid.

Synthetic, spectroscopic, and X-ray crystallographic studies on binuclear copper(II) complexes with a tridentate NNS-bonding 2-formylpyridine thiosemicarbazone ligand. The characterization of both neutral and deprotonated co-ordinated ligand structures

The preparation of the complexes [(CuLX)2](HL = 2-formylpyridine thiosemicarbazone) from the interaction of HL with the appropriate copper salt (X = CH3COO, Cl, NO3, or ClO4) or by reaction of an HL–KX mixture with copper(II) acetate monohydrate (X = Br or I) is described. Dissolution of [{CuL(CH3COO)}2] in H2SO4 or HCl yields the protonated ligand complexes [{Cu(HL)(SO4)}2] and [{Cu(HL)Cl2}2]·2H2O respectively. The complexes have been characterized by a variety of spectroscopic techniques and the crystal and molecular structures of [{CuL(CH3COO)}2] and [{Cu(HL)(SO4)}2] determined by single-crystal X-ray diffraction techniques from diffractometer data. Crystals of [{CuL(CH3COO)}2] are triclinic, space group P, with a= 8.827(3), b= 8.813(3), c= 8.997(3)A, α= 117.49(2), β= 110.96(3), γ= 91.65(3)°, and Z= 1. Crystals of [{Cu(HL)(SO4)}2] are monoclinic, space group C2/c, with a= 14.751(3), b= 9.138(2), c= 17.468(4)A, β= 104.91(2)°, and Z= 4. After full-matrix least-squares refinement the final R value was 0.027 for both complexes (2 216 and 2 206 observed reflections were used respectively). Both complexes consist of discrete centrosymmetric dimers, the monomeric units being bridged by two acetato or sulphato ligands. The copper atoms have a distorted square-pyramidal co-ordination geometry with three donor atoms (NNS) coming from L or HL to form a tricyclic ligating system. The fourth donor atom (oxygen) comes from the bridging CH3COO– or SO42– ion. The fifth co-ordination position is occupied by a less strongly bound oxygen from the second bridging anion.

The chromium, manganese, cobalt and copper complexes of human lactoferrin

Abstract The human milk protein, lactoferrin forms complexes of the type M2Lf (where M = Cr(III), Mn(III) or Co(III) and Lf = lactoferrin). The properties of these complexes and their electronic spectra are reported along with those of the known iron and copper complexes, Fe2Lf and Cu2Lf. For the latter complex, a d-d band, not previously reported, is seen at 677 nm. The spectral data confirm the suggestion that the metal binding sites in the protein are two or three tyrosyl residues and at least one nitrogen (probably from a hystidyl residue).

The reaction of the pyrophosphate ion with the antitumour complex [{CuL(CH3COO)}2] (HL=2-formylpyridine thiosemicarbazone) and the single-crystal X-ray structure of [(CuL)4P2O7]·nH2O

Abstract The preparation of the complex [(CuL)4P2O7]·nH2O (HL=2-formylpyridine thiosemicarbazone; n=9–12) from the reaction of Na4P2O7 with [{CuL(CH3COO)}2] is described. The complex has been characterized by a variety of physiochemical techniques and its crystal and molecular structure determined. Crystals of [(CuL)4P2O7]·nH2O are monoclinic, space group C2/c, with a=29.074(6), b=28.021(3), c=13.374(3) A, β=102.93(2)° and Z=8. The complex is tetranuclear, containing four CuL+ moieties linked by a bridging P2O74− anion. Each copper atom is in an approximately square pyramidal environment. The equatorial positions are occupied by a pyrophosphate oxygen, a pyridine nitrogen, an imine nitrogen and a thioamide sulfur, the latter three from the same L ligand. A weakly bound S atom from an adjacent L ligand, is in an axial position, thus completing the coordination sphere. Each tetranuclear [(CuL)4P2O7] molecule may be considered as a pair of dinuclear (CuL+)2 units linked by a P2O74− anion. Each dinuclear unit is further linked by the axial CuS bonds. The pyrophosphate ion, which displays a staggered conformation, plays an important role in the hydrogen bonding network involving phosphate oxygens, the thioamide and amine nitrogens of L, and the watet molecules in the structure. The variable temperature magnetic susceptibility of [(CuL)4P2O7]·nH2O is compared with that of [{CuL(CH3COO)}2] and in both cases the results are interpreted in terms of very weak antiferromagnetic coupling between the copper atoms. In the case of the pyrophosphate complex, the fact that the structure contains dinuclear (CuL+)2 units linked in pairs required that an interaction between the dinuclear units as well as the intramolecular J value be included to fit the magnetic data.

Sulphur ligand metal complexes. Part 15. [1]. Sulphurnitrogen donor ligand complexes of copper

The interaction of the following nitrogensulphur donor ligands with copper has been investigated: 2-(3,3-dimethyl-2-thiabutyl)benzimidazole (L1), 2-(3,3-dimethyl-2-thiabutyl)quinoline (L2), 2-ethylthioethylamine (L3), 2-(2-thiabutyl)pyridine (L4), 2-(2-pentafluorophenyl-2-thiaethyl)pyridine (L5), 2-methylthio-2-imidazoline (L6), and 2-methylthiobenzimidazole (L7). The copper(II) complexes CuLX2 (L = L1, L2, L3 or L4, X = Cl or Br), CuL2X2·H20 (L = L1, X = ClO4; L = L7, X = BF4), CuL2X2 (L = L3, L5 or L7, X = Cl or Br; L = L3 or L4, X = BF4; L = L3, X = ClO4; L = L7, X = NO3), [CuL2X]BF4 (L = L3, X = Cl; L = L4, X = Br), CuL32(SO4), CuL64 X2 (X = Cl, Br or BF4) and the copper(I) complexes CuL2Br, Cu(L2H)Br2 and CuL22(ClO4) have been isolated and structures proposed on the basis of conductivity, infrared, electronic and e.s.r. spectral measurements. The study shows that the use of sterically bulky thioether ligands can induce Cu(II) to adopt a pseudo-tetrahedral coordination as in the complexes CuLX2 (L = L1 or L2, X = Cl or Br). In the ligands L5, L6 and L7, the thioether sulphur does not coordinate strongly to Cu(II) if at all. E.s.r. data indicate that the Cu(II) complexes undergo extensive solvation and dissociation in methanol.

Preparation and characterization of complexes of the antitumour copper(II) 2-formylpyridine thiosemicarbazone (HL) system and the single-crystal X-ray structures of [{Cu(HL)(CF3CO2)}2][CF3CO2]2 and [Cu(HL)(H2O)(CLO4)2]·2H2O

The complexes [{Cu(HL)X2·nH2O (HL = 2-formylpyridine thiosemicarbazone, X = CF3CO2, F or I, n= 0; X = Br, n= 2) and [Cu(HL)(H2O)X2]·nH2O (X = ClO4, n= 2; X = NO3, n= 0) have been prepared from the reaction of [{CuL(MeCO2)}2] with the appropriate acid, HX. Also prepared were the deprotonated ligand complexes [(CuLX)2]·nH2O from the reaction of NaL with the appropriate copper(II) salt (X = F, n= 5.5; X =½SO4, n= 3) or by the reaction of [{CuL(MeCO2)}2] with the appropriate sodium salt, NaX (X = N3, n= 1; X = CN, n= 2). The complexes have been characterized by a variety of physicochemical techniques and the crystal and molecular structures of [{Cu(HL)(CF3CO2)}2][CF3CO2]2 and [Cu(HL)(H2O)(ClO4)2]·2H2O determined by single-crystal X-ray diffraction studies. Crystals of [{Cu(HL)(CF3CO2)}2][CF3CO2]2 are triclinic, space group P, with a= 9.6015(7), b= 10.837(1), c= 8.811(2)A, α= 100.71(1), β= 117.06(1), γ= 80.877(7)°, and Z= 1. The complex cation is a centrosymmetric dimer, the monomeric units being bridged by two CF3CO2– anions. The copper atoms have a distorted square-pyramidal co-ordination geometry with three donor atoms (NNS) coming from HL and the fourth donor (an oxygen) from the bridging anion. The fifth position is occupied by a less strongly bound oxygen from the second bridging anion. Crystals of [Cu(HL)(H2O)(ClO4)2]·2H2O are monoclinic, space group P21/c, with a= 12.9615(5), b= 9.7638(4), c= 14.9964(8)A, β= 111.580(4)°, and Z= 4. The complex is monomeric with a distorted tetragonal co-ordination around the copper atom. The four in-plane donor atoms are provided by HL (NNS) and an oxygen from a co-ordinated water molecule. Two weakly bound ClO4– ions occupy the fifth and sixth positions. In both complexes hydrogen-bonding schemes appear to be important in stabilizing them in the solid state. The differences in the bonding parameters for the Cu(HL)2+ and CuL+ systems are discussed and related to the fact that the S→CuII ligand-to-metal charge-transfer absorption (at ca. 400 nm) is always observed at higher energies for the HL complexes.

Reaction of nitrogen and sulphur donor ligands with the antitumour complex [{CuL(MeCo2)}2](HL = 2-formylpyridine thiosemicarbazone) and the single-crystal X-Ray structure of [CuL(bipy)]ClO4(bipy = 2,2′-bipyridyl)

The preparation of N- and S-donor ligand adducts with CuL+(HL = 2-formylpyridine thiosemicarbazone) is described. The N-donors, 2,2′-bipyridyl (bipy), 1,10-phenanthroline (phen) and 4-dimethylaminopyridine (dmap) give the complexes [CuL(bipy)]X (X = ClO4 or PF6), [CuL(bipy)]2SO4·8H2O, [CuL(phen)]PF6 and [CuL(dmap)2]PF6, which have been characterized by physical and spectroscopic techniques. The structure of one of the complexes, [CuL(bipy)]ClO4, has been determined by the single-crystal X-ray diffraction method: triclinic, space group P with a= 8.560(3), b= 9.452(4), c= 13.078(4)A, α= 106.35(3), β= 94.66(3), γ= 95.27(3)° and Z= 2. The complex contains discrete [CuL(bipy)]+ cations and ClO4– anions. The copper atom environment exhibits a distorted five-co-ordinate geometry. Three donor atoms (NNS) from L form a tricyclic ligating system with the remaining positions being occupied by bipy N atoms giving significantly different Cu–N distances of 1.986(4) and 2.179(4)A. Pentafluoro-(pftp), pentachloro-(pctp) and 4-nitro-thiophenolate (ntp) give S-donor complexes [{CuL(SR)}2]·nH2O (SR = pftp, n= 4; pctp, n= 0; ntp, n= 6). Thiolato co-ordination is proposed on the basis of spectroscopic evidence. With 2-mercaptobenzothiazole (Hmbt), 2-mercaptoimidazole (Hmi), 2-mercapto-1-methylimidazole (Hmmi) and 3-mercapto-4-methyl-1,2,4-triazole (Hmmt), either deprotonated ligand adducts of the type [CuL(A)](A = mbt, mi or mmt) or neutral ligand adducts [CuL(HA)2]PF6(HA = Hmmi or Hmi) are isolated. It is suggested that the thioamides co-ordinate via the imine nitrogen atom. The relevance of the results to proposed mechanisms for the antitumour activity of CuL+ is discussed.

The synthesis and single-crystal x-ray structure of [{Os3H(CO)10}3(S3C3N3)]; a novel osmium cluster containing three linked osmium triangles

Abstract The cluster [{Os 3 H(CO) 10 } 3 (S 3 C 3 N 3 )] has been prepared from the reaction of [Os 3 (CO) 10 (CH 3 CN) 2 ] with 2,4,6-trimercapto- 1,3,5-triazine (H 3 S 3 C 3 N 3 ) and the structure has been established by a single-crystal X-ray analysis. This latter, in conjunction with spectroscopic data, shows that [{Os 3 H(CO) 10 } 3 (S 3 C 3 N 3 )] contains three linked osmium triangles each with thiolate and hydride bridges across a common edge.