Ian D. Cunningham

Kinetic study of the H2O2 oxidation of phenols, naphthols and anilines catalysed by the haem octapeptide microperoxidase-8

A range of phenols, naphthols and anilines has been oxidised by hydrogen peroxide using microperoxidase-8 (MP-8) as a catalyst. The rate of the reaction is independent of the nature and concentration of the substrate over a limited range, confirming that oxidation of the catalyst is the rate-limiting step. The efficiency of the catalytic oxidation, as opposed to deactivation, has been defined in terms of relative catalytic efficiency; this is dependent on the nature, but not the concentration, of the substrate. This has been interpreted as kinetic evidence for a ‘substrate involved’ MP-8 decomposition pathway.

Chemistry of amidines. Part 1. Determination of the site of initial protonation in N′-pyridylformamidines

A series of substituted N,N-dimethyl-N′-pyridylformamidines has been synthesised and the pKa values of the conjugate acids have been measured in water at 25 °C. Consideration of the pka values shows that initial protonation is predominantly on the imino nitrogen of the amidine system rather than on the pyridyl nitrogen. The effect of the protonation on the 1H and 13C NMR spectra of the amidines is discussed.

PEROXIDATIC ACTIVITY OF HAEM OCTAPEPTIDE COMPLEXES WITH ANILINES, NAPHTHOLS AND PHENOLS

Complexation of the title substrates to microperoxidase-8 (MP-8) results in inhibition of the normal MP-8 catalytic pathway, but introduces an alternative pathway, probably leading to the same oxidised intermediate. This pathway must involve a different type of H2O2–MP-8 interaction to that proposed for HRP, and a preliminary interaction of peroxide with the porphyrin ring, rather than the Fe, of the MP-8:substrate complex is suggested for this pathway.

Identification of catalytic pathways in the peroxidatic reactions of the haem octapeptide microperoxidase-8

Reaction of microperoxidase-8 (MP-8) with H2O2 leads to the formation of an oxidized intermediate whose subsequent reduction by 2,4-dimethoxyphenol occurs in two stages and results in regeneration of MP-8. Analysis of the kinetics of these reactions in comparison with those of the normal peroxidatic reaction shows that at least four oxidized forms of MP-8 are capable of oxidizing the phenol. Possible structures and modes of action for these intermediates are discussed.

1H AND 15N NMR STUDIES OF N-SUBSTITUTED-N'-CYANOGUANIDINES

A series of N-aryl-N′-cyanoguanidines has been prepared and studied in [2H6]Me2SO by 1H and 15N NMR spectroscopy. The 15N NMR coupling patterns for natural abundance and 15N-enriched guanidines show unequivocally a structure with the CN conjugated with the cyano group. The invariance of δH for the nitrogen bound protons with guanidine concentration, the temperature variation, the lack of water-induced change in δH, the linear free energy relationship (LFER) analysis and coupling patterns, all show that no prototropic tautomerisation is occurring on the NMR timescale. The findings are considered in terms of possible dissociative and non-dissociative mechanisms.

Chemistry of amidines. Part 2. Substituent and solvent effects on rotational barriers in N′-pyridylformamidines

Values of ΔG‡ for rotation about the carbon–dimethylamino bond in a range of substituted pyridyl formamidines have been determined by 1H NMR spectroscopy in a small range of solvents. The correlation of ΔG‡ with σ– is interpreted in terms of a coplanar amidine and pyridine system. The variation of ΔG‡ with solvent is interpreted in terms of hydrogen bonding to the amino lone pair of the amidine.

Acid, base, and uncatalysed isomerisation of Z-to E-amidine. A mechanistic study

The Z-amidines (2Z) have been prepared by stereospecific reaction of nitrilium ion intermediates and the kinetics of interconversion into the E-amidines (2E) studied in aqueous solution at 25 °C. The interconversion is strongly catalysed by acid, so that at all pH values < 11, the acid-catalysed pathway (C–N bond rotation in the protonated species) dominates. A pH-independent reaction (uncatalysed nitrogen inversion) is observed over a narrow range at high pH while with one amidine (5aZ) carrying the most electron-withdrawing substituent, base catalysis (probably reversible addition of HO–) is unexpectedly observed. The more reactive amidines [e.g.(5c)] were formed and their isomerisations studied in situ; however, introduction of electron withdrawal in the substituent on the imino nitrogen [such as (5a)] or on the amino nitrogen [such as (2d)] permitted the isolation of pure Z-isomers.

Chemistry of amidines. Part 3. Analysis of conformation about the N′-pyridyl bond in N′-(2-pyridyl)formamidines

A conformational analysis of a series of N,N-dimethyl-N′-(2-pyridyl)formamidines and their conjugate acids using the 1H NMR nuclear Overhauser effect shows that they exist preferentially in the conformation in which the pyridine and the imino nitrogen lone pairs are anti. For compounds having electron-donating substituents the syn conformation becomes important on protonation.

Chemistry of amidines. Part 4. Analysis of conformation for a series of N′-pyridylformamidines by 1H NMR spectroscopic, molecular mechanical and semi-empirical molecular orbital methods

The results of NOE measurements for a series of N′-pyridylformamidines and their conjugate acids have been interpreted with the aid of molecular mechanical and semi-empirical molecular orbital calculations. Conformations about the pyridyl–Nim and the Cf–Nam bonds are determined by delocalisation of the Nam lone pair, dipolar interactions, steric interactions and, in the conjugate acids, long range interaction between the pyridyl N and the electron-deficient formyl H.

Chemistry of isocyanides. Part 2. Nucleophilic addition of hydroxide to aromatic isocyanides in aqueous dimethyl sulphoxide. Correlations of rate with a nucleophilicity function

A range of aromatic isocyanides has been found to undergo nucleophilic addition of hydroxide in aqueous dimethyl sulphoxide (DMSO) over the composition range 0–98.67 mol% DMSO. The rate of reaction increases as the aqueous content of the solutions is decreased. At compositions low in DMSO correlations of log kobs with H–+ log aw are linear with slopes of 0.47–0.50, while at higher levels of DMSO correlations are also linear, but with slopes of 0.73–0.90. The results are discussed in terms of a solvent-induced switch from a concerted to a stepwise mechanism. An unusually enhanced reactivity of m-nitrophenyl isocyanide is observed and possible explanations for this are considered.