Maximum-entropy determination of self-association distribution functions; daunorubicin and ATP Original Research Article

In the present paper we show how one can use the perturbation of some molecular optical property (for example circular dichroism or chemical shift) as a function of concentration to construct cluster distribution functions describing the self-association of molecules in solution. The optical data are first converted into data giving the variation of the average extent of clustering as a function of the total concentration and then, using straightforward thermodynamics, a set of moments of the cluster distribution function can be obtained. Utilizing the maximum-entropy method, the moments are then used to calculate approximate distribution functions, where the more moments that are used the better the approximation obtained. Given the probability distribution for clusters of different sizes one can then calculate the equilibrium constant for each stage of association. Thus one converts average degree of association into equilibrium constants without having to use any specific model. By this method one can clearly tell whether the equilibrium constants remain constant, increase, or decrease with the number of molecules in a cluster. We apply the method to literature data for two systems, namely daunorubicin, which has a strong tendency to cluster in solution, and Mg(ATP)2− which forms weaker clusters. We find that the successive equilibrium constants for adding a monomer to a cluster are approximately constant for daunorubicin but clearly decrease as a function of increasing cluster size for Mg(ATP)2−.