Structure elucidation, conformational analysis and thermal effects on membrane bilayers of an antimicrobial myricetin ether derivative

The membrane perturbing 3,7,4 ' ,5 ' -tetramethyl ether of myricetin 1 was isolated from Cistus monspeliensis i,. Its structure was elucidated and its conformational properties were explored using a combination of 2D NMR spectroscopy and computational chemistry. The obtained results showed that compound 1 adopts four enantiomeric pairs of low energy conformers characterized: (a) by an aromatic ring B twisted through rotation about C2-C1 ' bond from the rigid isoflavone ring; (b) a 4 ' -O-CH3 bond oriented out of the plane with equal probability upwards or downwards the phenyl ring B, while all the other O-CH3 bonds are oriented in the plane of the aryl ring. Two of these enantiomeric pairs are lowest in energy. These possible bioactive conformers are possibly stabilized by van Der Waals interactions. The 3 ' ,5-diacetyl derivative 2 of compound 1 was synthesized and its structure elucidation was achieved based on the chemical shift assignment of the parent compound 1. The Differential Scanning Calorimetry (DSC) results revealed that the degree of the thermal effects exerted by the flavonoids at dipalmitoylphosphatidyl choline (DPPC) bilayers followed the order 1 > 2 > myricetin. Their antimicrobial activity against Gram positive bacteria followed the same order.