On the Interactions of Melatonin/β-Cyclodextrin Inclusion Complex: A Novel Approach Combining Efficient Semiempirical Extended Tight-Binding (xTB) Results with Ab Initio Methods

Melatonin (MT) is a molecule of paramount importance in all living organisms, due to its presence in many biological activities, such as circadian (sleep-wake cycle) and seasonal rhythms (reproduction, fattening, molting, etc.). Unfortunately, it suffers from poor solubility and, to be used as a drug, an appropriate transport vehicle has to be developed, in order to optimize its release in the human tissues. As a possible drug-delivery system, beta-cyclodextrin (beta CD) represents a promising scaffold which can encapsulate the melatonin, releasing when needed. In this work, we present a computational study supported by experimental IR spectra on inclusion MT/beta CD complexes. The aim is to provide a robust, accurate and, at the same time, low-cost methodology to investigate these inclusion complexes both with static and dynamic simulations, in order to study the main actors that drive the interactions of melatonin with beta-cyclodextrin and, therefore, to understand its release mechanism.

Automated summary

In this work, a computational study supported by experimental IR spectra on inclusion MT/beta CD complexes is presented. The aim is to provide a robust, accurate, and low-cost methodology to investigate these inclusion complexes using both static and dynamic simulations, in order to study the main actors driving the interactions of melatonin with beta-cyclodextrin and to understand its release mechanism.