Tripod-like cationic lipids as novel gene carriers.

An innovative family of tridentate-cationic "single-chained lipids" designed to enhance DNA compaction and to promote endosomal escape was synthesized by coupling various lipids to a multibranched scaffold. DNA retardation assays confirmed the ability of the most members of the library to complex DNA. Classical molecular dynamics simulations performed on the lauryl derivative, bound to a short strand of DNA in aqueous solution supported these observations. These showed that two "arms" of the tripodal molecule are ideally suited to forming strong Coulombic interactions with two contiguous phosphate groups from the DNA backbone while the lipophilic tail stays perpendicular to the DNA helix. Gene transfer abilities of the library were assessed in multiple cell lines (CHO, Cos7, and 16HBE14o-) with some library members giving excellent transfection abilities and low cytotoxicity, supporting the use of this tripodal approach for the development of efficient gene delivery agents.

The ultrafast dynamics of hydrogen-bonded liquids: molecular structure-dependent occurrence of normal arrhenius or fractional Stokes-Einstein-Debye rotational diffusive relaxation.

The ultrafast rotational-diffusive dynamics of the peptide linkage model compounds N-methylacetamide (NMA), acetamide (Ac), and N,N-dimethylacetamide (DMA) have been studied as a function of temperature using optically heterodyne-detected optical Kerr effect (OHD-OKE) spectroscopy. Both NMA and Ac exhibit a non-Arrhenius temperature dependence of the rotational diffusive relaxation time. By contrast, the non-hydrogen-bonding DMA exhibits normal hydrodynamic behavior. The unusual dynamics of NMA and Ac are attributed to the decoupling of single-molecule rotational diffusive relaxation from the shear viscosity via a transition between stick and slip boundary conditions, which arises from local heterogeneity in the liquid due to the formation of hydrogen-bonded chains or clusters. This provides new insight into the structure and dynamics of an important peptide model compound and the first instance of such a phenomenon in a room-temperature liquid. The OHD-OKE responses of carboxylic acids acetic acid (AcOH) and dichloroacetic acid (DCA) are also reported. These, along with the terahertz Raman spectra, show no evidence of the effects observed in amide systems, but display trends consistent with the presence of an equilibrium between the linear and cyclic dimer structures at all temperatures and moderate-to-high mole fractions in aqueous solution. This equilibrium manifests itself as hydrodynamic behavior in the liquid phase.

Accurate equilibrium structures obtained from gas-phase electron diffraction data: sodium chloride.

A novel method has been developed to allow the accurate determination of equilibrium gas-phase structures from experimental data, thus allowing direct comparison with theory. This new method is illustrated through the example of sodium chloride vapor at 943 K. Using this approach the equilibrium structures of the monomer (NaCl) and the dimer (Na(2)Cl(2)), together with the fraction of vapor existing as dimer, have been determined by gas-phase electron diffraction supplemented with data from microwave spectroscopy and ab initio calculations. Root-mean-square amplitudes of vibration (u) and distance corrections (r(a) - r(e)) have been calculated explicitly from the ab initio potential-energy surfaces corresponding to the vibrational modes of the monomer and dimer. These u and (r(a) - r(e)) values essentially include all of the effects associated with large-amplitude modes of vibration and anharmonicity; using them we have been able to relate the ra distances from a gas-phase electron diffraction experiment directly to the re distances from ab initio calculations. Vibrational amplitudes and distance corrections are compared with those obtained by previous methods using both purely harmonic force fields and those including cubic anharmonic contributions, and the differences are discussed. The gas-phase equilibrium structural parameters are r(e)(Na-Cl)(monomer) = 236.0794(4) pm; r(e)(Na-Cl)(dimer) = 253.4(9) pm; and <(e)ClNaCl = 102.7(11) degrees. These results are found to be in good agreement with high-level ab initio calculations and are substantially more precise than those obtained in previous structural studies.

Gas electron diffraction study of the vapour over dimethylamine-gallane leading to an improved structure for dimeric dimethylamidogallane, [Me2NGaH2]2: a cautionary tale.

Dimethylamine-gallane is relatively slow to decompose in a closed system and vaporises at low temperature primarily as Me2(H)N.GaH3 molecules which can be trapped in a solid Ar matrix and characterised by their IR spectrum. Under the conditions needed to secure a useful gas electron diffraction (GED) pattern, however, the vapour was found to consist of dimeric dimethylamidogallane molecules, [Me2NGaH2]2, formed from the secondary amine adduct by elimination of H2, and the most reliable structure for which has been determined. Salient structural parameters (r(hl) structure) were found to be: r(Ga-N) 202.6(2), r(Ga-H) 155.6(8), r(N-C) 148.0(3), r(C-H) 111.2(6) pm; Ga-N-Ga 90.7(1), C-N-C 109.3(5), N-C-H 109.9(10) and H-Ga-H 119.4(42) degrees.

Gas-phase electron diffraction studies of the icosahedral carbaboranes, ortho-, meta- and para-C2B10H12.

The molecular structures of the three closo-carbaboranes, ortho-, meta- and para-C2B10H12, were experimentally determined using gas-phase electron diffraction (GED). All unique bond distances for ortho and meta carbaboranes were determined experimentally for the first time. For ortho-carbaborane (RG= 0.046), a model with C2v symmetry refined to give bond distances of 1.624(8) A for C-C, 1.093(8)A for C-H and 1.192(3)-1.196(3) A for B-H. For meta-carbaborane (RG= 0.040) a model with C2v symmetry refined to give a CC distance of 2.575(9) A. For para-carbaborane (RG= 0.062) a model with D5d symmetry refined to give a C-B bond distance of 1.698(3) A, B2-B3 of 1.785(1), B2-B7 of 1.774(4) and CC of 3.029(5)A. These GED structures are compared with geometries from other experimental diffraction methods (neutron, X-ray) and ab initio calculations.

Inter- and intramolecular hydrogen bonding in phenol derivatives: a model system for poly-L-tyrosine.

The ultrafast dynamics of solutions of phenol and two phenol derivatives--hydroquinone (1,4-benzenediol) and pyrocatechol (1,2-benzenediol)--have been studied with Optically Heterodyne-Detected Optical Kerr-Effect (OHD-OKE) spectroscopy. The solvents, methanol and acetonitrile, were selected to provide strong and weak solvent-solute hydrogen-bonding interactions, respectively, while pyrocatechol features an intramolecular hydrogen bond. Together these provide a series of model systems for polypeptides such as polytyrosine, which facilitate the direct study of inter- and intramolecular hydrogen bonding. A broad contribution to the Raman spectral density of the methanol solutions at frequencies between 150 and 300 cm(-1) has been observed that is absent in acetonitrile. This contribution has been assigned to solvent-solute hydrogen-bond stretching vibrations. The OHD-OKE response of poly-L-tyrosine has been measured and was found to contain a similar contribution. Density functional theory geometry optimizations and normal mode calculations have been performed using the B3LYP hybrid functional and 6-311++G** basis set. These have yielded a complete assignment of the low-frequency Raman and far-infrared spectra of pyrocatechol for the first time, which has provided information on the nature of the intramolecular hydrogen bond of pyrocatechol.

The molecular structure of tetra-tert-butyldiphosphine: an extremely distorted, sterically crowded molecule.

The molecular structure of tetra-tert-butyldiphosphine has been determined in the gas phase by electron diffraction using the new DYNAMITE method and in the crystalline phase by X-ray diffraction. Ab initio methods were employed to gain a greater understanding of the structural preferences of this molecule in the gas phase, and to determine the intrinsic P-P bond energy, using recently described methods. Although the P-P bond is relatively long [GED 226.4(8) pm; X-ray 223.4(1) pm] and the dissociation energy is computed to be correspondingly small (150.6 kJ mol(-1)), the intrinsic energy of this bond (258.2 kJ mol(-1)) is normal for a diphosphine. The gaseous data were refined using the new Edinburgh structure refinement program ed@ed, which is described in detail. The molecular structure of gaseous P(2)Bu(t)(4) is compared to that of the isoelectronic 1,1,2,2-tetra-tert-butyldisilane. The molecules adopt a conformation with C(2) symmetry. The P-P-C angles returned from the gas electron diffraction refinement are 118.8(6) and 98.9(6) degrees, a difference of 20 degrees, whilst the C-P-C angle is 110.3(8) degrees. The corresponding parameters in the crystal are 120.9(1), 99.5(1) and 109.5(1) degrees. There are also large deformations within the tert-butyl groups, making the DYNAMITE analysis for this molecule extremely important.