Malachy McCann

Synthesis and anti-Candida activity of copper(II) and manganese(II) carboxylate complexes: X-ray crystal structures of [Cu(sal)(bipy)]·C2H5OH·H2O and [Cu(norb)(phen)2]·6.5H2O (salH2=salicylic acid; norbH2=cis-5-norbornene-endo-2,3-dicarboxylic acid; bipy=2,2′-bipyridine; phen=1,10-phenanthroline)

Abstract The copper(II) complexes [Cu(salH)2(H2O)2]·0.5H2O (1) (salH2=salicylic acid) and [Cu2(asp)4]·3H2O (8) {aspH=acetylsalicylic acid (aspirin)} both react with imidazole (imid), 1,10-phenanthroline (phen) and 2,2′-bipyridine (bipy) giving [Cu(sal)(imid)] (2), [Cu(sal)(phen)] (3) and [Cu(sal)(bipy)]·C2H5OH·H2O (4). CuCl2·2H2O reacts with cis-5-norbornene-endo-2,3-dicarboxylic acid (norbH2) and NaOH giving [Cu(norb)]·H2O (9). Complexes 4 and 9 were crystallographically characterised. The above complexes, together with the related manganese(II) complexes, [Mn2(salH)4(H2O)4] (5), [Mn(salH)2(phen)] (6), [Mn(salH)2(bipy)]·H2O (7), [Mn(norb)H2O] (11) and [Mn(norb)(phen)2]·C2H5OH·H2O (12) and also the metal-free ligands were screened for their ability to inhibit the growth of the pathogenic yeast Candida albicans. 1,0-Phenanthroline and the phenanthroline complexes 6, 10b and 12 exhibited high anti-Candida activity with the manganese complexes 6 and 12 being the most potent.

Synthesis and catalytic activity of manganese(II) complexes of heterocyclic carboxylic acids: X-ray crystal structures of [Mn(pyr)2]n, [Mn(dipic)(bipy)2]·4.5H2O and [Mn(chedam)(bipy)]·H2O (pyr=2-pyrazinecarboxylic acid; dipic=pyridine-2,6-dicarboxylic acid; chedam=chelidamic acid(4-hydroxypyridine-2,6-dicarboxylic acid); bipy=2,2-bipyridine)

Abstract Reactions of manganese(II) acetate with 2-pyrazine carboxylic acid, 2,6-pyridinedicarboxylic acid and chelidamic acid (4-hydroxypyridine-2,6-dicarboxylic acid) yielded [Mn(pyr)2]n (1), [Mn(dipic)]·1.5H2O (2) and Mn(chedam)]·H2O (6), respectively. Reaction of 2 with 2,2′-bipyridine and 1,10-phenanthroline results in the synthesis of [Mn(dipic)(bipy)]·2H2O (3), [Mn(dipic)(bipy)2]·4.5H2O (4) and [Mn(dipic)(phen)2]·2H2O (5). Complex 6 reacted with 2,2′-bipyridine and 1,10-phenanthroline to give [Mn(chedam)(bipy)]·H2O (7) and [Mn(chedam)(phen)2]·3H2O (8), respectively. Molecular structures for 1, 4 and 7 were determined by X-ray crystallography. In 1 the structure is essentially polymeric with each pyrazine carboxylate anion coordinated to the manganese ion in a bidentate fashion using one carboxylate oxygen atom and the adjacent nitrogen. The second nitrogen is uncoordinated. For 4 the asymmetric unit consists of one tridentate dipicolinate ligand, two bidentate bipyridine molecules, four full-occupancy water molecules and one half-occupancy water molecule. The structure of 7 contains monomeric [Mn(dicarboxylate)(bipy)H2O] units in which the Mn(II) ions have very irregular six-coordinate geometry. Spectroscopic, magnetic and physical data for the complexes are presented. All of the manganese complexes catalytically disproportionate hydrogen peroxide in the presence of imidazole.

Copper(II) Complexes of Salicylic Acid Combining Superoxide Dismutase Mimetic Properties with DNA Binding and Cleaving Capabilities Display Promising Chemotherapeutic Potential with Fast Acting in Vitro Cytotoxicity against Cisplatin Sensitive and Resistant Cancer Cell Lines

The complexes [Cu(salH)(2)(H(2)O)] (1), [Cu(dipsH)(2)(H(2)O)] (2), {Cu(3-MeOsal)(H(2)O)(0.75)}(n) (3), [Cu(dipsH)(2)(BZDH)(2)] (4), [Cu(dipsH)(2)(2-MeOHBZDH)(2)]·EtOH (5), [Cu(sal)(phen)] (6), [Cu(dips)(phen)]·H(2)O (7), and [Cu(3-MeOsal)(phen)]·H(2)O (8) (salH(2) = salicylic acid; dipsH(2) = 3,5-diisopropylsalicylic acid; 3-MeOsalH(2) = 3-methoxysalicylic acid; BZDH = benzimidazole; 2-MeOHBZDH = 2 methanolbenzimidazole and phen =1,10-phenanthroline) were prepared and characterized. Structures of 4, 5, and 8 were determined by X-ray crystallography. Compounds 1-8 are potent superoxide dismutase mimetics, and they are inactive as inhibitors of COX-2 activity. Compounds 1, 4, and 5 exhibit moderate inhibition of COX-1. Complexes 6-8 display rapid micromolar cytotoxicity against cisplatin sensitive (breast (MCF-7), prostate (DU145), and colon (HT29)) and cisplatin resistant (ovarian (SK-OV-3)) cell lines compared to 1-5, and they exhibit potent in vitro DNA binding and cleavage capabilities.

A new rhodium(II) phosphate catalyst for diazocarbonyl reactions including asymmetric synthesis

Abstract A new homochiral Rh(II) complex, Rh{HCO3}2{(+)-phos}2·5H2O, where (+)phosH represents (S)-(+)-1,1′-binaphthyl-2,2′-diyl hydrogen phosphate, has been prepared and used as a catalyst for reactions of diazocarbonyl compounds leading to enantioselective 2,3-sigmatropic rearrangement (first example), C H insertion and aromatic cycloaddition

Insights into the mode of action of the anti-Candida activity of 1,10-phenanthroline and its metal chelates.

Metal complexes of malonie acid (metal = Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Ag(I)) were prepared and only the Ag(I) complex inhibited the growth of Candida albicans. Malonate complexes incorporating the chelating 1,10-phenanthroline (1,10-phen) ligand showed a range of activities: good (Mn(II), Cu(II), Ag(I)); moderate (Zn(II)); poor (Co(II), Ni(II)). Metal-free 1,10-phen and Ag(CH3CO2) were also highly active. The metal-free non-chelating ligands 1,7- phenanthroline and 4,7-phenanthroline were inactive and the Cu(II), Mn(II) and Zn(II) complexs of 1,7-phen displayed only marginal activity. Whereas the Cu(II) malonate/1,10-phen complex induces significant cellular oxidative stress the Zn(II) analogue does not.

Syntheses and X-ray crystal structures of cis-[Mn(bipy)2Cl2] · 2H2O · EtOH and cis-[Mn(phen)2Cl2] (bipy = 2,2′-bipyridine; phen = 1,10-phenanthroline); catalysts for the disproportionation of hydrogen peroxide

Abstract MnCl 2 ·4H 2 O reacts with 2,2′-bipyridine (bipy) to give cis -[Mn(bipy) 2 Cl 2 ] ( 1 ), and recrystallisation of 1 from ethanol gives cis -[Mn(bipy) 2 Cl 2 ]·2H 2 O·EtOH ( 2 ). MnCl 2 ·4H 2 O and 1,10-phenanthroline (phen react to form cis -[Mn(phen) 2 Cl 2 ] ( 3 ). In each case, the X-ray crystal structures of 2 and 3 show the manganese(II) atom to have a similar distorted octahedral geometry, and in both cases there is extended π-π stacking of the conjugated ring systems. Compared with MnCl 2 ·4H 2 O, 1 and 3 are much more efficient catalysts for the disproportionation of hydrogen peroxide. The catalytically active species are believed to be [Mn(bipy) 2 (H 2 O) 2 ] 2+ and [Mn(phen) 2 (H 2 O) 2 ] 2+ , respectively.

Copper(II) complexes of coumarin-derived Schiff bases and their anti-Candida activity.

The condensation of 7-amino-4-methyl-coumarin (1) with a number of substituted salicylaldehydes yielded a series of Schiff bases (2a-2k) in good yields. Subsequent reaction of these ligands with copper(II) acetate yielded Cu(II) complexes (3a-3k) and some were characterised using X-ray crystallography. All of the free ligands and their metal complexes were tested for their anti-Candida activity. A number of the ligands and complexes exhibited anti-Candida activity comparable to that of the commercially available antifungal drugs, ketoconazole and Amphotericin B.

Synthesis and fungitoxic activity of manganese(II) complexes of fumaric acid: X-ray crystal structures of [Mn(fum)(bipy)(H2O)] and [Mn(Phen)2(H2O)2](fum)·4H2O (fumH2=fumaric acid; bipy=2,2′-bipyridine; phen=1,10-phenanthroline)

Abstract The reaction of fumaric acid with Mn(CH 3 COO) 2 ·4H 2 O gives the polymeric complex {Mn(fum)} n ( 1 ). Complex 1 reacts with 2,2′-bipyridine in ethanol to yield [Mn(fum)(bipy)(H 2 O)] n ( 2 ). Reaction of 1 with 2 equiv. of 1,10-phenanthroline produces [Mn 2 (fum) 2 (phen) 2.5 ]·3H 2 O ( 3 ) and [Mn(phen) 2 (H 2 O) 2 ](fum)·4H 2 O ( 4 ). The molecular structures of 2 and 4 were determined by X-ray crystallography. In 2 the fumarate anions link the manganese ions so that each is seven coordinate, being bonded to a bidentate bipyridine, two bidentate carboxylates and one H 2 O molecule. In 4 the asymmetric unit contains a [Mn(phen) 2 (H 2 O) 2 ] 2+ cation, half of each of two independent fumarate anions and four lattice H 2 O molecules. The cations and anions are interconnected by water molecules hydrogen bonded to both coordinated water molecules and fumarate oxygens. The fumarate complexes, the metal free ligands and a number of simple manganese salts were each tested for their ability to inhibit the growth of Candida albicans . Only the ‘metal free’ 1,10-phenanthroline and its fumarate complexes exhibit fungitoxic activity

Manganese(II) complexes of hexanedioic and heptanedioic acids: X-ray crystal structures of [Mn(O2C(CH2)4CO2(phen)2H2O] · 7H2O and [Mn(phen)2(H2O)2][Mn(O2C(CH2)5CO2) [phen)2H2O](O2C(CH2)5CO2) · 12.5H2O

Mn(CH 3 CO 2 ) 2 ·4H 2 O reacts with ethanolic solutions of hexanedionic and heptanedioic acids ( ca 1:1 mol ratio) to produce the respective manganese(II) complexes [Mn(O 2 C(CH 2 ) 4 CO 2 )H 2 O] ( 1 ) and [Mn(O 2 C(CH 2 ) 5 CO 2 )] ( 2 ). Subsequent reaction of 1 and 2 with 1,10-phenanthroline (phen) ( ca 1:2 mol ratio) in aqueous ethanol gives [Mn(O 2 C(CH 2 ) 4 CO 2 )(phen) 2 H 2 O]·7H 2 O ( 3 ) and [Mn(phen) 2 (H 2 O) 2 ][Mn(O 2 C(CH 2 ) 5 CO 2 (phen) 2 H 2 O](O 2 C(CH 2 ) 5 CO 2 )·12.5H 2 O ( 4 ), respectively. Complexes 3 and 4 have been structurally characterised. The asymmetric unit in 3 has a manganese(II) atom coordinated to four nitrogen atoms from two chelating phenanthroline ligands, one oxygen atom from a unidentate (O 2 C(CH 2 ) 4 CO 2 ) −2 ligand and one oxygen atom from a water molecule which is in a cisoid position with respect to the diacid ligand. The asymmetric unit in 4 contains two mononuclear manganese(II) species, the dication [Mn(phen) 2 (H 2 O) 2 ] 2+ and the neutral manganese heptanedioate complex [Mn(O 2 (CH 2 ) 5 CO 2 )(phen)(H 2 O)], along with a non-coordinated (O 2 C(CH 2 ) 5 CO 2 ) 2− counter dianion. In the dication [Mn(phen) 2 (H 2 O) 2 ] 2+ the manganese atom is coordinated to four nitrogen atoms from two chelating phenanthroline ligands and two oxygen atoms from two cisoid water molecules. In the neutral fragment [Mn(O 2 C(CH 2 ) 5 CO 2 )(phen) 2 (H 2 O)] the metal atom is coordinated to four nitrogen atoms from two chelating phenanthroline ligands, one oxygen atom from a unidentate (O 2 C(CH 2 ) 5 CO 2 ) 2− ligand and one oxygen atom from a water molecule which is cis with respect to the coordinated carboxylate oxygen of the heptanedioate ligand. IR, magnetic and conductivity data for the complexes are given. All four complexes are catalysts for the disproportionation of H 2 O 2 in the presence of added imidazole.

Role of cell cycle events and apoptosis in mediating the anti-cancer activity of a silver(I) complex of 4-hydroxy-3-nitro-coumarin-bis(phenanthroline) in human malignant cancer cells

The central objective of the current study was to investigate the potential in vitro anti-proliferative effect of 4-hydroxy-3-nitro-coumarin (hncH), and the mixed-ligand silver (I) complex of 4-oxy-3-nitro-coumarin-bis(phenanthroline), [Ag(hnc)(phen)(2)] using four human-derived model cell lines. In addition, selected mechanistic studies were carried out using the most sensitive of the four cell lines. Results obtained show that the complex could decrease the proliferation of all four cell lines including neoplastic renal and hepatic, namely A-498 and HepG(2) cells, respectively, along with two non-neoplastic renal and hepatic cell lines, HK-2 and Chang, respectively. Furthermore, non-neoplastic hepatic cells (Chang) appeared to be less sensitive to the effect of the complex, but this effect was not replicated in the non-neoplastic renal (HK-2) cells. Based on IC(50) values [Ag(hnc)(phen)(2)] was shown to be almost four times more potent than cisplatin, using HepG(2) cells. In addition, the observed anti-proliferative effect was shown to be both dose- and time-dependent. Furthermore, the complex was shown to decrease DNA synthesis, but did not intercalate with it. Moreover, there was no evidence that P-glycoprotein-mediated multi-drug resistance was likely to decrease anti-proliferative activity. Cytological stains, analysis of genomic DNA, and biochemical assays [caspase-3 and -9 and cleaved poly(ADP-ribose)-polymerase protein] showed that cell death appeared to result from apoptosis, with the possibility of secondary necrosis. Additionally, flow cytometric analysis showed that the complex functioned through an alteration in cell cycle progression. Taken together, [Ag(hnc)(phen)(2)] has been shown to be a more potent anti-proliferative agent than cisplatin, capable of altering key biochemical events leading to cell death. Additional mechanistic studies are underway to probe more fully its mechanism of action.