Estimation of Dimerisation Constants from Complexatin‐Induced Displacements of ¹H‐NMR Chemical Shifts: Dimerisation of Caffeine

Abstract

Abstract The determination of the dimerisation constant ( K D ) for the weak self‐association of a compound C in dilute solution according to the equilibrium, 2C⇌C 2 is described. The method uses chemical shifts measured on a series of solutions of C at different concentrations: the optimum K D is defined by a linear regression best‐fit procedure, which simultaneously determines optimum values for δ o and also for δ ∞ , the intrinsic chemical shifts for nuclei in the monomer and dimer species. The dimerisation of caffeine in D 2 O is used as a model to demonstrate the working of the method and the quality of results obtained. The most probable value of K D for caffeine at 30.5° is found in the range 5.5–6.0 kg solution · mol −1 , and the enthalpy and entropy of dimerisation are found to be Δ H ⊖ = −15.1 kJ · mol −1 and Δ S ⊖ = −35.3 J · °C −1 · mol −1 , respectively. The influence of small errors in δ o on the confidence limits of K D is discussed.