Assessing Parameter Suitability for the Strength Evaluation of Intramolecular Resonance Assisted Hydrogen Bonding in o-Carbonyl Hydroquinones.

Intramolecular hydrogen bond (IMHB) interactions have attracted considerable attention due to their central role in molecular structure, chemical reactivity, and interactions of biologically active molecules. Precise correlations of the strength of IMHB's with experimental parameters are a key goal in order to model compounds for drug discovery. In this work, we carry out an experimental (NMR) and theoretical (DFT) study of the IMHB in a series of structurally similar o-carbonyl hydroquinones. Geometrical parameters, as well as Natural Bond Orbital (NBO) and Quantum Theory of Atoms in Molecules (QTAIM) parameters for IMHB were compared with experimental NMR data. Three DFT functionals were employed to calculated theoretical parameters: B3LYP, M06-2X, and ωB97XD. O…H distance is the most suitable geometrical parameter to distinguish among similar IMHBs. Second order stabilization energies ΔEij(2) from NBO analysis and hydrogen bond energy (EHB) obtained from QTAIM analysis also properly distinguishes the order in strength of the studied IMHB. ΔEij(2) from NBO give values for the IMHB below 30 kcal/mol, while EHB from QTAIM analysis give values above 30 kcal/mol. In all cases, the calculated parameters using ωB97XD give the best correlations with experimental ¹H-NMR chemical shifts for the IMHB, with R² values around 0.89. Although the results show that these parameters correctly reflect the strength of the IMHB, when the weakest one is removed from the analysis, arguing experimental considerations, correlations improve significantly to values around 0.95 for R².

Intramolecular hydrogen bond in biologically active o-carbonyl hydroquinones.

Intramolecular hydrogen bonds (IHBs) play a central role in the molecular structure, chemical reactivity and interactions of biologically active molecules. Here, we study the IHBs of seven related o-carbonyl hydroquinones and one structurally-related aromatic lactone, some of which have shown anticancer and antioxidant activity. Experimental NMR data were correlated with theoretical calculations at the DFT and ab initio levels. Natural bond orbital (NBO) and molecular electrostatic potential (MEP) calculations were used to study the electronic characteristics of these IHB. As expected, our results show that NBO calculations are better than MEP to describe the strength of the IHBs. NBO energies (∆Eij(2)) show that the main contributions to energy stabilization correspond to LP-->σ* interactions for IHBs, O1…O2-H2 and the delocalization LP-->π* for O2-C2=Cα(ß). For the O1…O2-H2 interaction, the values of ∆Eij(2) can be attributed to the difference in the overlap ability between orbitals i and j (Fij), instead of the energy difference between them. The large energy for the LP O2-->π* C2=Cα(ß) interaction in the compounds 9-Hydroxy-5-oxo-4,8, 8-trimethyl-l,9(8H)-anthracenecarbolactone (VIII) and 9,10-dihydroxy-4,4-dimethylanthracen-1(4H)-one (VII) (55.49 and 60.70 kcal/mol, respectively) when compared with the remaining molecules (all less than 50 kcal/mol), suggests that the IHBs in VIII and VII are strongly resonance assisted.

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

Lyotropic liquid crystals (LLCs) are mixtures of amphiphile molecules usually studied as mimetic of biological membrane. The equilibrium dynamics of tetradecyltrimethyl ammonium cation (TTA+) molecules forming nematic LLCs (LNLCs) is guided by a dive-in mechanism where TTA+ molecules spontaneously leave and re-enter the bicelle. Of note, this dynamic behavior could be exploited to produce drug nano-delivery systems based on LNLCs. Therefore, the understanding of the effect of pharmaceutically interesting molecules in the dynamics of the dive-in mechanism should be crucial for drug delivery applications. In this work, we studied the effects of l-DOPA in the equilibrium dynamics of TTA+ bicelles forming LNLCs, employing a transdisciplinary approach based on 2H-NMR together with molecular modeling and molecular dynamics simulations. Our data suggest that l-DOPA perturbs the kinetic of the dive-in mechanism but not the thermodynamics of this process. As whole, our results provide fundamental insights on the mechanisms by which l-DOPA govern the equilibrium of LNLCs bicelles.

Counterion and composition effects on discotic nematic lyotropic liquid crystals II. Ion exchange and molecular dynamics.

The static fluorescence quenching of pyrene by bromide, at the interface of mixed TTAC/TTAB discotic nematic lyotropic liquid crystals, allowed an estimation of the equilibrium constant for the exchange of chloride by bromide. The affinity of the interface for bromide is much higher than for chloride (K(Br-/Cl-) = 13.2). For a molecular level understanding of the experimental results of this and the preceding paper, 20 ns molecular dynamics (MD) simulations were calculated for samples with TTAB/TTAC molar percent ratios 100/0 (A), 50/50 (B) and 0/100 (C). The increment in the concentration of chloride induces a wider distribution of ammonium headgroups along the axis normal to the bilayer surface, increasing the width of the interface. The charge density profile of simulation B shows that the concentration of bromide is higher than the concentration of chloride in the vicinity the ammonium headgroups. The short range contribution to the electrostatic energy from the ammonium-ammonium repulsion is 291.7 kJ/mol for TTAC and 195.6 kJ/mol for TTAB, and the short range ammonium-halide interaction is -6166 kJ/mol for TTAC and -6607 kJ/mol for TTAB, from simulations A and C, respectively. These results are in agreement with a more neutralized TTAB interface. Consistently, the electric dipole moments of water are significantly more aligned with the larger electric field of the TTAB interface.

Counterion and composition effects on discotic nematic lyotropic liquid crystals I. Size and order.

Counterion and composition effects on the size and interface dynamics of discotic nematic lyotropic liquid crystals made of tetradecyltrimethylammonium halide (TTAX)-decanol (DeOH)-water-NaX, with X = Cl(-) and Br(-), were investigated using NMR and fluorescence spectroscopies. The dynamics of the interface was examined by measuring deuterium quadrupole splittings from HDO (0.1% D(2)O in H(2)O) and 1,1-dideuterodecanol (20% 1,1-dideuterodecanol in DeOH) in 27 samples of each liquid crystal. Aggregation numbers, N(D), from 15 samples of each mesophase were obtained using the fluorescence of pyrene quenched by hexadecylpyridinium chloride. N(D) of TTAB and TTAC are about 230+/-30 and 300+/-20, respectively. N(D) of TTAC increases with increasing concentration of all mesophase components, whereas TTAB shows no correlation between size and composition. The dimension of these aggregates prevents the occurrence of undulations, previously observed in lamellar phases. The quadrupole splitting of decanol-d(2) in TTAC is about 5 kHz smaller than in TTAB, and the splitting of HDO is observed only in TTAB. All results are consistent with a more dynamic TTAC interface. The TTAC aggregate should be more dissociated from counterions and the excess ammonium-ammonium electrostatic repulsions contribute to increase the mobility of the interface components.