Surface active benzodiazepine-bromo-alkyl conjugate for potencial GABAA-receptor purification

ANAHÍ DEL V. TURINA; GISELA J. QUINTEROS; BENJAMIN CARUSSO; ELIZABETH L. MOYANO; MARÍA A. PERILLO

ORGANIC & BIOMOLECULAR CHEMISTRY

ROYAL SOC CHEMISTRY

Año: 2011 vol. 9 p. 5737 - 5747

1477-0520

A conjugable analogue of the benzodiazepine 5-(2-hydroxyphenyl)-7-nitro-benzo[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 mM and expanded a model membrane packed up to 35 mN m-1 when penetrating in it from the aqueous phase. BDC exhibited surface activity, with a collapse pressure p = 9.8 mN m-1 and minimal molecular area Amin = 52 A˚ 2/molecule at the closest molecular packing, resulted fully and non-ideally mixed with a phospholipid in a monolayer up to a molar fraction x ~= 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 mM and expanded a model membrane packed up to 35 mN m-1 when penetrating in it from the aqueous phase. BDC exhibited surface activity, with a collapse pressure p = 9.8 mN m-1 and minimal molecular area Amin = 52 A˚ 2/molecule at the closest molecular packing, resulted fully and non-ideally mixed with a phospholipid in a monolayer up to a molar fraction x ~= 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 mM and expanded a model membrane packed up to 35 mN m-1 when penetrating in it from the aqueous phase. BDC exhibited surface activity, with a collapse pressure p = 9.8 mN m-1 and minimal molecular area Amin = 52 A˚ 2/molecule at the closest molecular packing, resulted fully and non-ideally mixed with a phospholipid in a monolayer up to a molar fraction x ~= A-R with an inhibition binding constant Ki = 0.89 mM and expanded a model membrane packed up to 35 mN m-1 when penetrating in it from the aqueous phase. BDC exhibited surface activity, with a collapse pressure p = 9.8 mN m-1 and minimal molecular area Amin = 52 A˚ 2/molecule at the closest molecular packing, resulted fully and non-ideally mixed with a phospholipid in a monolayer up to a molar fraction x ~= Ki = 0.89 mM and expanded a model membrane packed up to 35 mN m-1 when penetrating in it from the aqueous phase. BDC exhibited surface activity, with a collapse pressure p = 9.8 mN m-1 and minimal molecular area Amin = 52 A˚ 2/molecule at the closest molecular packing, resulted fully and non-ideally mixed with a phospholipid in a monolayer up to a molar fraction x ~= p = 9.8 mN m-1 and minimal molecular area Amin = 52 A˚ 2/molecule at the closest molecular packing, resulted fully and non-ideally mixed with a phospholipid in a monolayer up to a molar fraction x ~= Amin = 52 A˚ 2/molecule at the closest molecular packing, resulted fully and non-ideally mixed with a phospholipid in a monolayer up to a molar fraction x ~=x ~= 0.1. A geometrical?thermodynamic analysis along the p?A phase diagram predicted that at low xBDC (<0.1) and at all p, 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 London-type 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 recognized through the CNZ moiety. p?A phase diagram predicted that at low xBDC (<0.1) and at all p, 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 London-type 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 recognized through the CNZ moiety. p, 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 London-type 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 recognized through the CNZ moiety. via its terminal bromine atom while GABAA-R might be recognized through the CNZ moiety.