Surface active benzodiazepine-bromo-acyl conjugate for potential GABAA-receptor purification.

TURINA, A. V; QUINTEROS, G.J; CARUSO B.; MOYANO E.L.; PERILLO M.A.

ORGANIC & BIOMOLECULAR CHEMISTRY

ROYAL SOC CHEMISTRY

Año: 2011 vol. 9 p. 5737 - 5747

1477-0520

A conjugable analogue of the benzodiazepine 5-(2-hydroxiphenyl)-7-nitrobenzo[e][1,4]diazepin-2(3H)-one containing a bromide C12-aliphatic chain (BDC) at nitrogen N1 was synthesized. One-pot preparation of this benzodiazepine derivative was achieved using microwave irradiation giving 49% yield of the desired product. BDC inhibited FNZ binding to GABAA-R with an inhibition binding constant Ki=0.89 µM and expanded a model membrane packed up to 35 mN/m when penetrating in it from the aqueous phase. BDC exhibited surface activity, with a collapse pressure 9.8 mN/m and minimal molecular area Amin=52 Å2/molecule at the closest molecular packing, resulted fully and non-ideally mixed with a phospholipid in a monolayer up to a molar fraction 0.1. A geometrical -thermodynamic analysis along the π-A phase diagram predicted that at low XBDC (<0.1) and at all π, including the equilibrium surface pressures of bilayers, dpPC-BDC mixtures dispersed in water were compatible with the formation of planar-like structures. These findings suggest that, in a potential surface grafted BDC, this compound could be stabilize though Londontype interactions within a phospholipidic coating layer and/or through halogen bonding with an electron-donor surface via its terminal bromine atom while GABAA-R might be recognize through the CNZ moiety.