An application of flexible constraints in Monte Carlo simulations of the isobaric-isothermal ensemble of liquid water and ice Ih with the polarizable and flexible mobile charge densities in harmonic oscillators model

The hydrations of Na+ and K+ were investigated by means of Monte Carlo simulations with refined ab initio based potentials. These interaction potentials include intramolecular relaxation, polarizability and many-body nonadditive effects. Care was taken to ensure proper convergence of the MC runs and that the statistical samples were large enough. As a result, agreement was attained with all experimental data available for the hydration of the ions. The water molecules in the first hydration shell were found to have the same intramolecular geometries and dipole moments as those of the bulk. Furthermore, their dipoles were not aligned to the electric field produced by the ion, but quite tilted. The hydration number for the sodium was found to be 5 or 6 water molecules, whereas the potassium’s hydration number had a probability distribution ranging from 5 to 10. From an analysis of the energetic contributions of each hydration shell to the total enthalpy of hydration we propose that the hydrated ions have a distinct behavior. Sodium has a stronger interaction with its first hydration shell than potassium, giving the latter a more flexible structure.

Amphotericin B is an antimycotic agent that has been studied for a long time, both because of its pharmacological action and the interest in understanding how this ionic channel works. It has been proposed that the channel is formed by a barrel of monomers, and that the presence of sterol is needed for the formation of such a barrel. As a matter of fact this need of a sterol has been used as a guiding idea in attempts to design derivatives more efficient in the discrimination of the cholesterol containing membranes, as compared to the ergosterol containing ones, henceforth diminishing the unwanted side effects in its pharmacological use. In this work we show that unitary channels that appear in a cholesterol containing membrane also appear when this membrane is free of cholesterol. We prove this to be the case for two membranes, a biological one, asolectin, and a synthetic one, DMPC. We then advance the idea that the role of sterols in the formation of the amphotericin B channel is related to the effects they have on the structure of the membrane itself, rather than to a direct involvement in the channel formation. We further look into the effect that different cholesterol concentrations in the membrane produce on the single channel properties.

Ab initio calculations were performed to study the stability of various pyrophosphate species in the gas phase: H 4 P 2 O 7 , H 3 P 2 O 7 -, H 2 P 2 O 7 2-, HP 2 O 7 3-, P 2 O 7 4-, and their complexes with Mg 2+ . It is found that the metal cation allows the existence of highly charged anions in the gas phase. We also study the isomerization reactions Mg‚H 2 P 2 O 7 f (H 2 PO 4 ‚Mg‚PO 3 ), (Mg‚HP 2 O 7 ) -f (HPO 4 ‚Mg‚PO 3 ) -, and (Mg‚P 2 O 7 ) 2f (PO 4 ‚Mg‚PO 3 ) 2-, at the self-consistent-field (SCF) and second-order perturbation (MP2) levels of the theory, using a 6-31+G** basis set with diffuse and polarization functions. Other basis sets, including one of valence triple ζ plus polarization (vTZP) quality, were employed to check for the convergence of the results. It is found that the same mechanism occurs for the isomerizations of the three species: one of the P-O bridging bonds of the reactant is longer than the other, and the route to the products proceeds through its elongation. This asymmetry is induced by the metal cation in the case of the evenly charged anions. In all cases the metal cation coordinates the transition states and the leaving groups. The structures found for the complexes (H 2 PO 4 ‚Mg‚PO 3 ), (HPO 4 ‚Mg‚PO 3 ) -, and (PO 4 ‚Mg‚PO 3 ) 2are different from those reported previously, the metal cation being enclosed by the two phosphates. The activation barrier increases with the charge of the anion, from ∆G°q ) 5.6 kcal/mol for the neutral complex Mg‚H 2 P 2 O 7 , to ∆G°q ) 10.4 kcal/mol for the monoanion (Mg‚HP 2 O 7 ) -, to ∆G°q ) 13.5 kcal/mol for the dianion (Mg‚P 2 O 7 ) 2-. The positive value found for the energy of the isomerization (Mg‚P 2 O 7 ) 2f (PO 4 ‚Mg‚PO 3 ) 2-, ∆G°q ) 1.8 kcal/mol, predicts the synthesis to be spontaneous in the gas phase, opposite of what occurs in the aqueous solution. This result supports the view that the hydration energy makes a large contribution to the energy of hydrolysis. The gas-phase hydrolysis reaction H 2 O + Mg 2+ + H 2 P 2 O 7 2f Mg 2+ + H 2 PO 4-+ H 2 PO 4is also studied as a multistep reaction, involving the isomerization of H 2 O + (Mg‚H 2 P 2 O 7 ) f H 2 O + (PO 3 ‚Mg‚H 2 PO 4 ) as an intermediate step. It is found that the equilibrium in the gas phase yields H 2 PO 4 ‚Mg‚H 2 PO 4 as the final species; an energy input is required for separating the metal cation from the phosphate anions.

Using a simple model it is shown that the cost of constraining a hydrated potassium ion inside a narrow nanopore is smaller than the cost of constraining the smaller hydrated sodium ion. The former allows for a greater distortion of its hydration shell and can therefore maintain a better coordination. We propose that in this way the larger ion can go through narrow pores more easily. This is relevant to the molecular basis of ion selective nanopores and since this mechanism does not depend on the molecular details of the pore, it could also operate in all sorts of nanotubes, from biological to synthetic.