What is the hydrophobic interaction contribution to the stabilization of micro-hydrated complexes of trimethylamine oxide (TMAO)? A joint DFT-D, QTAIM, and MESP study

Abstract

Micro-hydrated trimethylamine oxide (TMAO) has been investigated using a rangeseparated-hybrid functional including empirical dispersion correction. Electrophilic and nucleophilic sites on TMAO and water clusters have been identified using the molecular electrostatic potential (MESP). The nature of the chemical bonding in the different isomers of the micro-hydrated complexes has been investigated with the topological analysis of the electron density (QTAIM) method. For complexes containing one to four water molecules, the strongest intermolecular interactions consist in hydrogen bonding between the oxygen atom of the TMAO and hydrogen atoms of water molecules. From five water molecules, interactions between water molecules become the main source of stabilization of the most stable isomer. From four stationary points corresponding to the 1:1 (TMAO:H 2 O) complex, we determined the minimum distances between water molecules and central TMAO allowing the latter molecule to be encapsulated within a water clathrate-type cage. Optimization of TMAO encapsulated within two water cages (5 12 and 5 12 6 2) suggests that only in the case of the 5 12 6 2 water cage the insertion of TMAO, the preservation of the hydrogen bonding between water molecules is energetically favorable. The interaction energy between one inserted TMAO and the 5 12 6 2 water cage was calculated to be around 150 kJ/mol with respect to the ground state of two partners. This result suggest that a thorough investigation of mono-hydrated complexes may be particularly relevant to identify the most suitable water cage for encapsulating a given solute.

Microhydration of a Carbonyl Group: How does the Molecular Electrostatic Potential (MESP) Impact the Formation of (H2O)n:(R2C═O)Complexes?

“…This means that when trying to maximize the interactions between solute and water dimer, the structures obtained after geometry optimization are more stable than when the starting point is a monohydrated complex and a water molecule. This result is consistent with other work suggesting that without more electrophilic or more nucleophilic sites than the ones available on water clusters, a segregation of water molecules is observed around the solute -. This means that the interaction of water clusters with the solute are energetically preferential in such a case than the interaction of separate water molecules.…”

“…This result is consistent with other work suggesting that without more electrophilic or more nucleophilic sites than the ones available on water clusters, a segregation of water molecules is observed around the solute. 55 - 48 This means that the interaction of water clusters with the solute are energetically preferential in such a case than the interaction of separate water molecules.…”

“…In line with these researches, an approach based on the identification of all the electrophilic and nucleophilic sites potentially available between both partners, was proposed. In this approach, structures that may lead to maximize interactions between complementary sites on both partners are built up prior to geometry optimizations. ,,− This approach was used in the present study, and it is detailed in the Methods.…”

On the relevance of the electron density analysis for the study of micro-hydration and its impact on the formation of a peptide-like bond

“…65,66,67 However, it should be noticed that in the case of "simple" hydrogen bonding interactions, such as those studied in the present article, the BCP allow to highlight non-covalent interactions. [68][69][70][71][72][73][74][75][76][77][78][79] DFT calculations still remain the most appropriate approach when searching for reaction paths involving multiple non-covalent interactions between multiple partners. The choice of the level of calculation is crucial to the quality of the results obtained.…”