title: Surface active benzodiazepine-bromo-alkyl conjugate for potential GABAA-receptor purification.
abstract: A conjugable analogue of the benzodiazepine 5-(2-hydroxyphenyl)-7-nitro-benzo[e][1,4]diazepin-2(3H)-one containing a bromide C(12)-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 GABA(A)-R with an inhibition binding constant K(i) = 0.89 μM 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 π = 9.8 mN m(-1) and minimal molecular area A(min) = 52 Å(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≅ 0.1. A geometrical-thermodynamic analysis along the π-A phase diagram predicted that at low x(BDC) (<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 London-type interactions within a phospholipidic coating layer and/or through halogen bonding with an electron-donor surface via its terminal bromine atom while GABA(A)-R might be recognized through the CNZ moiety.
authors.affiliation: Biofísica-Química, Cátedra de Química Biológica, Departamento de Química, Facultad de Ciencias Exactas, Físicas y Naturales, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: A V
authors.initials: AV
authors.lastname: Turina
authors.forename: G J
authors.initials: GJ
authors.lastname: Quinteros
authors.forename: B
authors.initials: B
authors.lastname: Caruso
authors.forename: E L
authors.initials: EL
authors.lastname: Moyano
authors.forename: M A
authors.initials: MA
authors.lastname: Perillo
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D001966:Bromine / Q000737:chemistry*; D002417:Cattle; D002998:Clonazepam / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D018757:GABA Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D054879:Halogenation; D008051:Lipid Bilayers / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding; D011963:Receptors, GABA-A / Q000302:isolation & purification* / Q000378:metabolism*; D013499:Surface Properties; D013570:Synaptic Membranes / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D018757:GABA Modulators; D008051:Lipid Bilayers; D010743:Phospholipids; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D002998:Clonazepam; D001966:Bromine