Thermodynamics and ²H NMR Study on the Insertion of Small Quinones into a Discotic Nematic Lyotropic Liquid Crystal

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 (2)H 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 Na2 SO4 in water. (2)H NMR quadrupole splittings (ΔνQ ) and longitudinal relaxation times (T1) from HQ-d6, Q-d4, DecOH-α-d2, partially deuterated water, and SDS-d25 were measured and several molecular dynamics trajectories were also calculated. In particular, ΔG, ΔH, and ΔS 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 kJ mol(-1) for HQ and Q, respectively.

Using solution state NMR spectroscopy to probe NMR invisible gelators

“…[17][18][19][20] Results and discussion Functionalised dipeptides can be extremely effective gelators. [17][18][19][20] Results and discussion Functionalised dipeptides can be extremely effective gelators.…”

“…Approaches similar to ours have been used to glean valuable information on surface-solute interactions in a variety of systems including clays and liquid crystals. [17][18][19][20]…”

Subtle chemical modification for enrichment of Fmoc-amino acid at a phospholipid interface

“…Molecular mechanics computational simulations were performed to examine the feasibility of the formation of H-bonds between the DMPA and Fmoc-Y molecules. 37,38 Three H-bonds were detected using in vacuo simulations, see Fig. 6.…”

l-DOPA modulates the kinetics but not the thermodynamic equilibrium of TTA+amphiphiles forming lyotropic nematic liquid crystals

“…5,6 Recently, the use of biodegradable copolymers of glycolic and lactic acids used via nasal L-DOPA administration, have attract the attention of many investigators 7 In recent years, mixtures of amphiphilic molecules in solutions received signicant attention as potential delivery systems. Among these, solutions made of orientationally ordered discotic aggregates (bicelles 8 among others), termed as lyotropic nematic liquid crystals (LNLCs), exhibit several uses such as, to grow oriented carbon nanotubes, [9][10][11] to synthetize silica and metals containing regularly oriented nanopores and, [12][13][14][15][16][17] as membrane mimetics, [18][19][20] and as micro-lubricants. 21,22 Of note, more recently, LNLCs has been proposed as simple but versatile carriers for pharmaceutical formulations to avoid the metabolic clearance and to maintain constant plasma concentration of drugs.…”