Thermodynamics of Pyridine and 1-Alkyl-Pyridinium Complexes of Protohaemin in Aqueous Solution

1 In alkaline aqueous solution (pH > 10) protohaemin forms a green coloured pyridine complex containing two ligands per haemin dimer. The thermodynamics of this reaction is characterized by a considerable entropy change due to hydrophobic interactions between both partners. 2 Similar haemin complexes are formed by N-alkyl-pyridinium halides. The absorption spectra are nearly identical to those of the corresponding pyridine complexes although there is no possibility of interaction with the positively charged haemin iron. Pyridinium cations develop a higher affinity towards haemin than the neutral pyridines. This behaviour is attributed to electrostatic attractions between the propionylic groups of porphyrin and the positively charged pyridinium salts. 3 The introduction of methyl groups intensifies the haemin complex stability both of the pyridines and the pyridinium salts. In order of increasing methylation of the ligands the reaction entropy increases. 4 Following the substitution of pyridine in position 4 by a cyano group or following the transition from N-alkyl-pyridinium halides to N-alkyl-quinolinium halides the affinity towards haemin increases and the thermodynamics show a decrease of the reaction enthalpy whilst the entropy of the system changes only little. For this behaviour π-donor-acceptor interactions should be responsible. 5 The results demonstrate the contribution of several types of chemical bond in the reaction of protohaemin with ligands. Apart from the well investigated coordinative linkage to the iron atom, π-donor-acceptor and hydrophobic interactions between ligands and the porphyrin system as well as ionic bonds between the propionylic groups of the porphyrin and positively charged ligands contribute to their haemin complex formation. 6 The significance of the results is discussed with regard to the haemin-protein interaction in haemoproteins.