HOW IMPORTANT IS WATER IN THE PREORGANIZATION OF POLYAMMONIUM HOST MOLECULES

We present Monte Carlo and Molecular Dynamics simulations on polyammonium compounds in order to assess the importance of water in the preorganization upon molecular recognition of macrocyclic poly-electrolytes in solution. The Monte Carlo simulations coupled to free energy calculations lead to a quantitative estimate of the rotational barrier around the C-C bond of H3N+-CH2-CH2-NH3+ in water, thus with the gas phase rotational barrier to the potential of mean force or free energy variation upon conformational interconversion. The Molecular Dynamics simulations of macrocycles build from several -NH2+-CH2-CH2-NH2+- and -NH2+-CH2-CH2-O-units permit us to picture the importance of water microstructures on flexible receptors for various anions (Cl-, ATP4-, ADP3-...). Both calculations lead to the result that water stabilizes conformations a priori unstable in gas phase. Microstructures of water or the gross effect of hydration permit the existence of gauche forms of -NH2+-CH2-CH2-NH2+- units, and thus stabilize converging positively charged binding sites. The convergence of repulsive sites is necessary in order to properly bind the various anionic substrates.