A medicinal chemistry perspective on melting point: matched molecular pair analysis of the effects of simple descriptors on the melting point of drug-like compounds

Abstract

The influence of simple molecular descriptors on the melting point temperature (T_m) has been investigated using a matched molecular pair (MMP) analysis. This method has been used to identify small structural differences between pairs of molecules which are related to changes in T_m. Our analysis shows that the number of hydrogen bond donors, hydrogen bond acceptors and rotatable bonds has a significant effect on the T_m of a molecule. Hydrogen bond donors have the most pronounced effect. Furthermore, the studies reveal that not ClogP but rather the number of bromine and iodine atoms has a marked effect on the T_m. The results of our MMP analysis are discussed within the context of drug solubility optimization.