Hélène Berthod

Quantum-mechanical studies on the conformation of phospholipids. the effect of water on the conformational properties of the polar head

We have shown in a previous paper [l] that the polar heads of the phospholipids manifest an intrinsic preference towards highly folded structures stabilized by a strong intramolecular hydrogen bond (ethanolamines) or electrostatic interaction (cholines) between the phosphate group and the cationic head. This type of structure is in fact observed in organic solvents [2]. In the present note we are studying the effect of hydration on the conformation of the polar head. Beforehand we relate, however, some complementary results on the free model molecule of fig.1. In reference [ 1 ] , the computations have been performed for this compound by the SCF ab initio procedure using Gaussian orbitals in the ST0 3G basis set. In view of an extension of computations to larger systems, the calculations have been repeated by the PCILO method [3,4]. In this case they have been performed both for ethanolamine phosphate (EP) (fig.1, R = H) and for choline phosphate (CP) (fig.1, R = CHs). The geometrical input data were taken from the crystal X-ray structure of GPE and GPC, respectively [5,6]. The PCILO conformational energy maps, with

Quantum mechanical studies of environmental effects on biomolecules. An ab initio study of the hydration of dimethylphosphate

Abstract STO 3G SCF computations are used to determine the most favorable sites of water fixation and the lability of the binding on the dimethylphosphate anion. A nearly circular region of attraction for water surrounds each of the anionic oxygens and a number of other possible hydration sites are found with very similar binding energies. As a result, many possibilities exist for the constitution of the first hydration shell which is shown to be able to accommodate up to six water molecules.

Quantum-mechanical studies of environmental effects on biomolecules VI.Ab initio Studies on the hydration scheme of the phosphate group

Ab initio SCF computations using the STO 3G basis set have been performed on the hydration scheme of the dimethylphosphate anion (DMP−) within the “supermolecule” approach. This model compound represents the phosphate group in nucleic acids, phospholipid components of membranes and a number of other important biological structures. In the first place the principal hydration sites for the fixation of a water molecule have been established and this was followed by the determination of the polyhydration scheme of the first solvation shell, which may involve up to six water molecules. The effect of hydration on the relative stabilities of thegg,gt andtt forms of (DMP−) was evaluated. The study was extended to the computation of the energies of interaction in the second and third hydration shells and the conclusion was reached that organized hydration around (DMP−) is essentially limited to two hydration shells with possible residual organization of a third shell around specific sites. The structure of the bound water was investigated. Charge transfer is observed from (DMP−) to the bound water, the perturbation extending essentially to the first and with decreasing intensity, to the second hydration shell.

The molecular electrostatic potential of the dimethyl phosphate anion: An ab initio study

Abstract The molecular electrostatic potential of the dimethyl phosphate anion in its most stable conformation is evaluated with ab initio STO 3G wavefunctions. The anionic oxygens are seen to be surrounded by a circular zone of nearly constant negative potential whereas discrete smaller potential wells occur in the neighbourhood of the ester oxygens.

An SCFab initio investigation of the “through-water” interaction of the phosphate anion with the Na+ cation

SCFab initio computations in the supermolecule approach were carried out for the study of the hydration scheme of the dihydrogen phosphate anion, of the sodium cation and for the investigation of the direct and the through-water interaction of these two charged species. It is found that the energy balances of the direct phosphate-Na+ binding, involving their prior dehydration, or their through-water binding, allowing them to conserve their hydration shells, are of the same order of magnitude, indicating the competitivity of the two processes. This situation results in the existence of multiple possibilities for phosphate-Na+-water association. Appreciable energies of interaction exist between the different subunits of such systems. The Na+ cation and to a somewhat lesser extent the phosphate anion have a polarizing effect upon the charge distribution in the system over relatively appreciable distances. On the contrary, the charge transfers between the different components of the system are interpretable essentially in terms of displacements between adjacent units only.

An ab initio study of the effect of the 3d orbitals of phosphorus on the properties of the phosphate group

A large number of properties of the dimethylphosphate anion (DMP−), model system for the phosphate group of the nucleic acids and the phospholipid components of membranes, has been investigated by the SCF ab initio procedure including the 3d orbitals of the phosphorus atom in the gaussian basis set and the results of the computations were compared with similar results obtained previously without taking these orbitals into account. The properties investigated include the conformational states of DMP with respect to the torsion about the P-Oester bonds, the distribution of the electronic charges, the molecular electrostatic potentials generated by DMP−, the characteristics of the molecular orbitals, particularly the electronic isodensity maps, the hydration scheme. Qualitatively, the introduction of the 3d orbitals modifies little the general aspects of the results obtained for most of the properties studied. On the quantitative level significant, although generally not great, modifications may be noticed with respect to some features of these properties. One of the strongest influences of the introduction of the 3d orbitals concerns the decrease of the net electronic charges in DMP−.

Quantum mechanical studies of environmental effects on biomolecules

SCFab initio computations have been performed on the structure, molecular potential and hydration scheme of thiourea in view of a comparison with urea and more generally as a model of the conjugated S=CNH-group as compared to O=CNH-. In contrast to the carbonyl oxygen, both σ and π acceptor, the sulfur atom of the thiocarbonyl is a σ donor but a π acceptor and this results in an enhancement of the double-bond character of thiourea. The CN bond is less attractive for a proton than urea. The hydration scheme indicates a maximum number of four water molecules directly bound to thiourea.

Binding of cations and the conformation of the phosphodiester linkage

Contrary to CNDO results, ab initio SCF computations indicate that binding of Na+ and Mg++ to the phosphodiester linkage leaves unperturbed its preferences for a gg conformation about the P-Oester bonds.

Experimental and quantum-chemical studies of the dipole moments of quinoline and indole

Abstract The magnitude and direction of the electric dipole moments of indole and quinoline have been determined experimentally and calculated by quantum-mechanical methods. The measured values are 2.08 D and 2.22 D, the directions form angles of 50° and 182° with the bond common to both rings in indole and quinoline, respectively. These results are in good agreement with the predicted magnitudes of 1.83 D and 2.08 D and with the angles of 42° and 179°, respectively.

Electrostatic molecular potentials in hydrogen-bonded systems

A study is made of the modifications of the electrostatic molecular potential brought about by hydrogen bonding both in the hydrogen-bond region itself and in the external regions of the proton-acceptor and proton-donor molecules. Systems up to four successive units in a chain of donor-acceptors are considered. The possibility of obtaining a satisfactory picture of the global potential by a simple superposition of the potentials of the individual units is evaluated.