Metal complexes as potential ligands : the deprotonation of aminephenolate metal complexes

The cationic nickel, copper and zinc complexes of tris-(2-hydroxybenzyl)-aminoethylamine (H6TrenSal) have been deprotonated using potassium hydroxide. The nickel complex can be sequentially deprotonated to form a series of compounds namely, [(H6TrenSal)Ni]+, [(H6TrenSal)Ni] and "[(H6TrenSal)Ni]K". The latter is isolated as a mixture of species namely [{(H6TrenSal)Ni}K(EtOH)]2, [{(H6TrenSal)Ni}K(EtOH)2-μ-OH2]2 and [{(H6TrenSal)Ni}K(EtOH)2-μ-EtOH]2, which co-crystallise in a roughly 50:27.5:22.5 ratio. In contrast the deprotonation of [(H6TrenSal)M]+ (M = Cu, Zn) results in the formation of tetrameric complexes [({(H6TrenSal)Ni}K(OH2)2)4(μ4-OH2)]

A study of the nitroprusside anion and some of its analogues

Sodium nitroprusside is a potent vasodilator and is widely used for lowering the blood pressure during major surgery. The physiological response is said to occur due to a nitrosation reaction at the smooth muscle membrane. The use of sodium nitroprusside has been restricted due to its ability' to release toxic cyanide in-vivo and in-vitro, which can cause severe complications during surgery. Chapter one is a study of the aqueous chemistry of sodium nitroprusside with amines and thiols. It is shown that steric factors play an important role and that thiols are more reactive than amines. The information is used to evaluate the chemical changes expected at the smooth muscle membrane and possible mechanisms for biochemical action. If the toxicity of nitroprusside anion cannot be aleviated the information can be used to evaluate the potential of other inorganic complexes as potential hypertensive agents. Chapter two deals with the biochemical and medical problems associated with sodium nitroprusside therapy. The interaction of the complex with human erytthrocytes is explored and the reasons for cyanide release are discussed. The toxicity associated with the complex is shown to be impossible to eradicate completely and short term measures to minimise the effects are given. Chapter three explores the implications of the nitrosyl stretching frequency and how its value could be used to indicate whether a compound would be expected to exhibit nitroprusside-type chemistry. The reactivity of five nitrosylpentacyanometallates with the simple reagents previously discussed in chapter one are investigated to show that the nitrosyl group can be positive, neutral or negative and that this information could be easily acquired from the stretching frequency of the nitrosyl group in the infra-red. A value for the nitrosyl stretching frequency is given, above which a compound would be expected to exhibit nitroprusside-type chemistry. These compounds would be expected to be vasodilators

Tetradentate Schiff base beryllium complexes

The structure of (BeSalen)2 is reported. The incompatibility of the geometry of the beryllium with the inflexibility of the Salen ligand gives rise to a rare dimeric bis-didentate motif

Schiff base complexes of copper and zinc as potential anti-colitic compounds

The design, synthesis and activity of polymodal compounds for the treatment of inflammatory bowel disease are reported. The compounds, being based on a metal-Schiff base motif, are designed to degrade during intestinal transit to release the bioactive components in the gut. The compounds have been developed sequential with the biomodal compounds combining copper or zinc with a salicylaldehyde adduct. These compounds were tested in a formalin induced colonic inflammation model in BK:A mice. From these studies a trimodal compound based on a zinc Schiff base analogue of Sulfosalazine were designed. This was tested against a trinitrobenzenesulfonic acid (TNB) induced colitic model in Wistar rats. The use of two models allows us to test our compounds in both an acute and a chronic model. The trimodal compound reported is observed to provide anticolitic properties in the chronic TNB induced colitis model commensurate with that of SASP. However, the design of trimodal compound still has the capacity for further development. This the platform reported may offer a route into compounds which can markedly outperform the anti-colitic properties of SASP

The nickel, copper and zinc complexes of a potentially heptadentate nitrogen donor ligands

The synthesis of the potentially heptadentate ligands, tris-(2-aminobenzylidene)amino-ethylamine (L3) and tris-(o-aminobenzyl)aminoethylamine (L4) are reported. Complexes of L3 with nickel copper and zinc have been synthesised and characterised. However, the nickel and zinc compounds are observed to re-arrange during the procedures used to produce samples for X-ray diffraction analysis. In both cases aniline groups are found to migrate to give rise to unique but related coordinated polyamine species. A rational route which allows for the reduction of the imine function in L3 is presented giving rise to a heptadetate ligand (L4) which contains primary, secondary and tertiary amines. Having removed the reactive imine function, the synthesized nickel and copper complexes follow the expected synthetic and structural pattern with the nickel complex being observed to be octahedral and the copper(II) complex five coordinate. The zinc complex is in contrast different. As observed for L3, it is possible to generate simple ZnL3 complexes but these are prone to intramolecular cyclisation where an aniline nitrogen couples with the secondary amine to form a coordinated indizine

Determination of metal ion concentrations by SERS using 2,2’-bipyridyl complexes

Surface enhanced Raman scattering (SERS) can generate characteristic spectral “fingerprints” from metal complexes, thus providing the potential for the development of methods of analysis for the identification and quantitation of a range of metal ions in solution. The advantages include sensitivity and the use of one ligand for several metals without the need for a specific chromophore. Aqueous solutions of Fe(II), Ni(II), Zn(II), Cu(II), Cr(III) and Cd(II) in the presence of excess 2,2′-bipyridyl (bipy) were analysed using SERS. Specific marker bands enabled the identification of each metal ion and the limit of detection for each metal ion was estimated. Two of the ions, Zn(II) and Cu(II), could be detected below the World Health Organisation's (WHO) recommended limits for drinking water at levels of 0.22 and 0.6 mg L−1, respectively

The interaction of silver(II) complexes with biological macromolecules and antioxidants

Silver is widely used for its antimicrobial properties, but microbial resistance to heavy metals is increasing. Silver(II) compounds are more oxidizing and therefore have the potential to overcome resistance via extensive attack on cellular components, but have traditionally been hard to stabilize for biological applications. Here, the high oxidation state cation was stabilised using pyridinecarboxylate ligands, of which the 2,6-dicarboxypyridine Ag(II) complex (Ag2,6P) was found to have the best tractability. This complex was found to be more stable in phosphate buffer than DMSO, allowing studies of its interaction with water soluble antioxidants and biological macromolecules, with the aim of demonstrating its potential to oxidize them, as well as determining the reaction products. Spectrophotometric analysis showed that Ag2,6P was rapidly reduced by the antioxidants glutathione, ascorbic acid and vitamin E; the unsaturated lipids arachidonic and linoleic acids, model carbohydrate β-cyclodextrin, and protein cytochrome c also reacted readily. Analysis of the reaction with glutathione by NMR and electrospray mass spectrometry confirmed that the glutathione was oxidized to the disulfide form. Mass spectrometry also clearly showed the addition of multiple oxygen atoms to the unsaturated fatty acids, suggesting a radical mechanism, and cross-linking of linoleic acid was observed. The seven hydroxyl groups of β-cyclodextrin were found to be completely oxidized to the corresponding carboxylates. Treatment of cytochrome c with Ag2,6P led to protein aggregation and fragmentation, and dose-dependent oxidative damage was demonstrated by oxyblotting. Thus Ag2,6P was found to be highly oxidizing to a wide variety of polar and nonpolar biological molecules

Intracellular Photophysics of an Osmium Complex bearing an Oligothiophene Extended Ligand

This contribution describes the excited-state properties of an Osmium-complex when taken up into human cells. The complex 1 [Os(bpy)2(IP-4T)](PF6)2 with bpy=2,2′-bipyridine and IP-4T=2-{5′-[3′,4′-diethyl-(2,2′-bithien-5-yl)]-3,4-diethyl-2,2′-bithiophene}imidazo[4,5-f][1,10]phenanthroline) can be discussed as a candidate for photodynamic therapy in the biological red/NIR window. The complex is taken up by MCF7 cells and localizes rather homogeneously within in the cytoplasm. To detail the sub-ns photophysics of 1, comparative transient absorption measurements were carried out in different solvents to derive a model of the photoinduced processes. Key to rationalize the excited-state relaxation is a long-lived 3ILCT state associated with the oligothiophene chain. This model was then tested with the complex internalized into MCF7 cells, since the intracellular environment has long been suspected to take big influence on the excited state properties. In our study of 1 in cells, we were able to show that, though the overall model remained the same, the excited-state dynamics are affected strongly by the intracellular environment. Our study represents the first in depth correlation towards ex-vivo and in vivo ultrafast spectroscopy for a possible photodrug. © 2020 The Authors. Published by Wiley-VCH Gmb