Intramolecular Weak Interactions in the Thermodynamic Stereoselectivity of Copper(II) Complexes with Carnosine–Trehalose Conjugates

Abstract

The interactions of metal ions with chiral molecules are of particular interest for relevant biochemical processes, as many of them are made possible only with a selected chirality of the stereocenters. In this work we report a study of the stereoselectivity of copper(II) complexes with D-trehalose-L-carnosine and D-trehalose-D-carnosine as a prototypical case of natural chirality selection. The interest in L-carnosine dipeptide is compounded by its antioxidant and antitumor properties, which are further enhanced when combined with D-trehalose. Potentiometric, calorimetric, and UV/circular dichroism (CD) spectroscopic measurements show that the copper(II) dimer of D-trehalose-L-carnosine is more stable than the D-trehalose-D-carnosine diastereoisomeric copper(II) dimer (log β(L)(22-2) - log β(D)(22-2) = 3.6). Free-energy calculations highlight that the cause of this different behavior lies with different intramolecular weak interactions between the diastereoisomers. The different pattern of hydrogen bonds and the different CH-π interactions between the π-electron-rich imidazole and the α-glucose rings are more favorable by 5 kcal mol(-1) in the L dimer.