Shape Theory and DFT Methods in Complete Route and Dissociation Mode of the O-H Bond in betanidin and molecular interactions

Betanidine (Bd) is a nitrogenous metabolite with significant bioactive potential influenced by pH. Its free radical scavenging activity and deprotonation pathway are crucial to studying its physi-cochemical properties. Our purpose is to establish the route and dissociation mode of the O-H bond of Bd from the complete set of possible deprotonation routes via pka and geometric de-scriptors. We use the direct approximation method to obtain the value of pka and perform geo-metric filtering through a descriptor called Riemann distance (RD), an emerging concept from shape theory. After exploring the complete set of permutations, we show that the successive deprotonation process does not inherit the local energy minimum, and the commutativity of the paths does not hold either. The RD reached a non-expected clusterization of the performance via pKa of a complete list of deprotonation routes. These results suggest including geometric relationships between the arrangement of the parent molecule and the corresponding locus of the deprotonated structures. We use our own algorithm based on shape theory to determine the protein's active site automatically, and molecular dynamics confirmed the results of the molecular docking of Bd in protonated and anionic form with the enzyme aldose reductase (AR). Also, we calculate the descriptors associated with the SET and SPLET mechanisms.