Thermodynamic and electronic and electron spin resonance spectroscopic investigation of the co-ordinating properties of 4-azaoctane-1,8-diamine (spermidine) in aqueous solution

The reason for the exchange of copper(II)-containing proteins with spermidine (4NH-od), according to a non-immunogenic mechanism for retardation of tumour growth, has been explored from a thermodynamic standpoint. Of the two complexes found in aqueous solution at physiological pH, [Cu(H-4NH-od)]3+ and [Cu(4NH-od)]2+, only the latter has the possibility of exchange. Its relatively high stability constant arises from a favourable enthalpy contribution, due to the full co-ordination of the three nitrogen atoms in a tetragonally distorted octahedral structure. This complex contains one seven-membered chelate ring fused to another six-membered ring. In the protonated spermidine complex the primary nitrogen atom of the tetramethylene chain is protonated. The spectroscopic (electronic and e.s.r.) properties of these two complexes have been determined. The protonation behaviour of spermidine has been also studied thermodynamically and the successive enthalpy and entropy values are explained on the basis of a tautomeric process which exists in symmetrical triamines.