Alkyl and aromatic isocyanide binding to haem complexes

Abstract

Equilibrium constants for the binding of ethyl (EIC), n-butyl (BIC), p-toluenesulphonylmethyl (TMIC) and 2,6-dimethylphenyl isocyanides (DIMPI) to an imidazole-haem complex in toluene and aqueous detergent micelle solutions were determined. In contrast to an earlier study, which indicated that the large affinities of myoglobin for binding DIMPI and 2,6-diethylphenylisocyanide (DEPI) relative to EIC were due to an electronic effect, the present study shows a similarity in binding constants for EIC, BIC, and DIMPI to the imidazole-haem complex in toluene, suggesting no such electronic effect is present. The measured hydrophobic effect (KDIMPI/KEIC = 11) cannot account for the large binding constant reported for DIMPI relative to the binding of EIC to myoglobin. Based on the results of these model studies, the equilibrium binding constant for DIMPI to myoglobin has been re-measured and the standard free energy of binding has been analysed by a more recent method.

Heme−Peptide Models for Hemoproteins. 1. Solution Chemistry of N-Acetylmicroperoxidase-8

“…Aggregation of AcMP8 in Aqueous Solution. An effective method for assessing concentration-dependent aggregation phenomena in solutions of metalloporphyrins is to determine the degree of adherence of the solution to Beer's law over the solute concentration range of interest 7a. Deviation from Beer's law signals aggregation of the absorbing species, while a single set of isosbestic points reflect a simple equilibrium between two species 8a.…”

“…Reflecting the change in spin state with time, the low-spin bands 13b at 537.0 nm (Q v ) and 564.9 nm (Q o ) diminish in intensity while a shoulder initially at 608.5 nm generates the characteristic CT band at 601.7 nm of an S = 5 / 2 ferric porphyrin complex axially ligated by an anionic oxygen ligand,13b which becomes the dominant spectroscopic feature in the visible spectrum after ∼100 h. There is also a concurrent shift in the B band from 407.0 to 394.8 nm as the low-spin starting material is consumed. Aggregation becomes more pronounced at t > 60 h and, in its final stages, is earmarked by distinct hypochromism of the B band, accompanied by hyperchromism of the spectrum in the N band region, which is characteristic of heme aggregates 7a…”

“…Hemoproteins, such as myoglobin, cytochrome c peroxidase, many plant peroxidases, and cytochrome c ‘, exhibit axial coordination of the heme group by a single histidyl residue from the protein. 1c,d A biomimetic analog for these hemoproteins should therefore support an appended imidazole base that can compete effectively for one of the coordination sites at the metal in the presence of solvent and exogenous ligands. − One of the main complications encountered with simple biomimetic systems, for example [M(PPIX)] n + , [M(OEP)] n + , and [M(TPP)] n + species, is their low solubility in aqueous solution. Physical studies on such systems have therefore depended on the use of organic solvents, mixed solvents, and detergents to circumvent aggregation . In fact, the propensity of simple metalloporphyrins, including those with appended solubilizing groups, to aggregate at fairly low concentrations in aqueous solution , and the difficulty of preparing mixed-ligand complexes 11 have frequently compromised 12 the application of such systems in biomimetic studies.…”

Structural, Magnetic, and Dynamic Characterization of the (dxz,dyz)4(dxy)1 Ground-State Low-Spin Iron(III) Tetraphenylporphyrinate Complex [(p-TTP)Fe(2,6-XylylNC)2]CF3SO3

“…Extensive thermodynamic and kinetic studies of alkyl isocyanide complexation to hemoglobin, myoglobin, − and other heme proteins − have been reported, but many questions still remain. First, despite the accuracy of these methods, conflicting results persist with regard to the binding of aryl isocyanides to myoglobin. , Thus, the intrinsic electronic effect on ligand binding associated with differences between alkyl and aryl isocyanides is still under debate. Second, the reason complexation of isocyanides with the ferric state is possible with cytochromes P450, whereas no ligation is observed with myoglobin and hemoglobin, is still not clear.…”