Molecule Formation Energy and Atomic Charge Effectiveness of Membrane-Active Diacyl Derivatives of Dibenzo-18-Crown-6

In this study, we present an investigation into the impact of substituent length within the benzene ring of diacyl derivatives of dibenzo-18-crown-6 (DB18C6) on the charges exhibited by oxygen atoms in the macrocycle. Our analysis reveals that the oxygens located at positions 1 and 4 of the nearest pyrocatechol group, situated at a separation of two carbon atoms from the benzene ring substituent, exhibit only minimal changes in charge when compared to oxygens located at positions 3 and 6, located at three carbon atoms. These may indicate that "sandwich" structures form during complex formation. Our research has revealed a correlation between the molecule formation energy of diacyl derivatives of DB18C6 and the enthalpy (ΔH) of complex formation. Specifically, the PM3 method was utilized to calculate the molecule formation energy, which showed an increase in energy from 4',4"-diacetyl-DB18C6 to 4',4"(5")-divaleryl-DB18C6. Similarly, data obtained from the MM+ technique demonstrated a rise in molecule formation energy from 4',4"-diacetyl DB18C6 to 4',4"(5")-divaleryl-DB18C6, and in both cases, this value remained at a close level achieved for 4',4"(5")-divaleryl-DB18C6. Specifically, we observed a gradual increase in molecule formation energy from 4',4"-diacetyl-DB18C6 to 4',4"(5")-divaleryl-DB18C6, which was consistent with the corresponding increase in ΔH and Ca2+ ionophore activity.