Mannich bases of hydroxycoumarins: synthesis, DFT/QTAIM computational study and assessment of biological activity.

The synthesis of six Mannich bases derived from hydroxycoumarins was carried out in moderate yields, two of these derivatives were described for the first time. Conformational analysis was performed through DFT theoretical calculations explaining the formation of stable six membered rings based on intramolecular hydrogen bonds within the structure. These findings were correlated with the antiproliferative activity. The biological activity of the Mannich bases through their antiproliferative activity in the HeLa cancer cell line is described for the first time, showing that the compounds were able to inhibit proliferation in cervical cancer by more than 60%. Likewise, the theoretical modeling of the photophysical properties was realized with promising results, showing that the HOMO-LUMO energies of the new compounds present the lowest electronic gap values for those with donor groups in their structure, which makes them potential fluorophores.

New paths of cyanogenesis from enzymatic-promoted cleavage of ß-cyanoglucosides are suggested by a mixed DFT/QTAIM approach.

Cyanogenesis is an enzyme-promoted cleavage of ß-cyanoglucosides; the release of hydrogen cyanide is believed to produce food poisoning by consumption of certain crops as Cassava (Manihot esculenta Crantz). The production of hydrogen cyanide by some disruption of the plant wall is related to the content of two ß-cyanoglucosides (linamarin and lotaustralin) which are stored within the tuber. Some features about the mechanistic bases of these transformations have been published; nevertheless, there are still questions about the exact mechanism, such as the feasibility of a difference in the kinetics of cyanogenesis between both cyanoglucosides. In this work, we have performed a theoretical analysis using DFT and QTAIM theoretical frameworks to propose a feasible mechanism of the observed first step of the enzyme-catalyzed rupture of these glucosides; our results led us to explain the observed difference between linamarin and lotaustralin. Meanwhile, DFT studies suggest that there are no differences between local reactivity indexes of both glucosides; QTAIM topological analysis suggests two important intramolecular interactions which we found to fix the glucoside in such a way that suggests the linamarin as a more reactive system towards a nucleophilic attack, thus explaining the readiness to liberate hydrogen cyanide.