Abstract
The ability to locally tune solute-water interactions and thus control the hydrophilic/hydrophobic character of a solute is key to control molecular self-assembly and to develop new drugs and biocatalysts; it has been a holy grail in synthetic chemistry and biology. To date, the connection between (i) the hydrophobicity of a functional group; (ii) the local structure and thermodynamics of its hydration shell; and (iii) the relative influence of van der Waals (dispersion) and electrostatic interactions on hydration remains unclear. We investigate this connection using spectroscopic, classical simulation and ab initio methods by following the transition from hydrophile to hydrophobe induced by the step-wise fluorination of methyl groups. Along the transition, we find that water-solute hydrogen bonds are progressively transformed into dangling hydroxy groups. Each structure has a distinct thermodynamic, spectroscopic and quantum-mechanical signature connected to the associated local solute hydrophobicity and correlating with the relative contribution of electrostatics and dispersion to the solute-water interactions.
Highlights
The ability to locally tune solute–water interactions and control the hydrophilic/hydrophobic character of a solute is key to control molecular self-assembly and to develop new drugs and biocatalysts; it has been a holy grail in synthetic chemistry and biology
We find that the hydration shell of each fluoromethyl group contains structures consisting of water hydroxy groups that point to the solute
We have investigated the sequential fluorination of a methyl group and the associated changes in hydrophobicity, hydration shell structure and thermodynamics
Summary
The ability to locally tune solute–water interactions and control the hydrophilic/hydrophobic character of a solute is key to control molecular self-assembly and to develop new drugs and biocatalysts; it has been a holy grail in synthetic chemistry and biology. The connection between (i) the hydrophobicity of a functional group; (ii) the local structure and thermodynamics of its hydration shell; and (iii) the relative influence of van der Waals (dispersion) and electrostatic interactions on hydration remains unclear We investigate this connection using spectroscopic, classical simulation and ab initio methods by following the transition from hydrophile to hydrophobe induced by the step-wise fluorination of methyl groups. Tuning hydrophobicity by manipulating hydrogen bonds has been a longstanding goal and challenge in materials science,[8,9,10,11,12,13] organic chemistry[14,15,16] and supramolecular chemistry.[17,18,19,20] the usual strategies employed to modify hydrogen bond patterns (the simplest being methylation and hydroxylation) result in changes in molecular surface area and topology, meaning that water–solute and water–water hydrogen bonds are simultaneously affected The challenge in such strategies is often perceived as the prediction of which hydrogen bonds are broken, formed or perturbed, and how they will change a solute’s hydrophobicity. Self-modeling curve resolution (SMCR)[38,40,41] was used to obtain minimum area non-negative solute-correlated (SC) spectra from pairs of pure water and solution spectra that were collected under identical experimental conditions (as described above)
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