Abstract

A detailed description of the distribution, interaction, and dynamics of molecules with biological activity dissolved in a hydrophobic bilayer, a simple model of a biological membrane, provides valuable information for a better understanding of drug functioning, which can be very useful in drug design. Here we present an H-2 NMR and molecular dynamics study on the insertion, distribution, interactions, and thermodynamics of two biologically active molecules, 9,10-dihydroxy-4,4-dimethyl-1,4,5,8-tetrahydroanthracen-1-one (HQ), with anticancer activity, and 4,4-dimethyl-1,4,5,8,9,10-hexahydroanthracen-1,9,10-trione (Q) a fungicide, dissolved in a nematic discotic lyotropic liquid crystal (ndllc) composed of sodium dodecylsulphate (SDS), decanol (DecOH) and Na2SO4 in water. H-2 NMR quadrupole splittings ((Q)) and longitudinal relaxation times (T-1) from HQ-d(6), Q-d(4), DecOH--d(2), partially deuterated water, and SDS-d(25) were measured and several molecular dynamics trajectories were also calculated. In particular, G, H, and S profiles for the process of both molecules crossing the bilayer were estimated. It was evidenced that the insertion of both molecules into the aggregate is a spontaneous process, and the molecules are mainly distributed in the internal side of the interface. Addition of HQ or Q decreased the mobility of all aggregate components, but this effect was more pronounced for HQ. The rotational correlation time of Q allowed an estimate of 5.3 cP for the microviscosity inside the ndllc aggregate, in the order of previously measured values in similar environments. Both guest molecules display similar free-energy profiles for the process of crossing the bilayer, with a calculated barrier height of 25 and 36 kJmol(-1) for HQ and Q, respectively.