Medium Effect on the Rotational Barrier of N,N,N′-Trimethylurea and N,N,N′-Trimethylthiourea: Experimental and Theoretical Study

Abstract

The solvent effect for rotation about the conjugated C-N(CH(3))(2) bond has been studied for N,N,N'-trimethylurea (TMU) and N,N,N'-trimethylthiourea (TMT) by dynamic NMR and theoretical calculations. The experimental part comprised the measurement of activation parameters (DeltaH(++), DeltaS(++), and DeltaG(++)) by DNMR in CD(2)Cl(2), CD(3)OD, and D(2)O/CD(3)OD solutions. In methanol, TMU and TMT present similar rotational barriers, 11.3 +/- 0.6 and 10.5 +/- 0.3 kcal/mol, respectively. However, in D(2)O/CD(3)OD solution TMU has its barrier raised to 12.4 kcal/mol, whereas that of TMT remains unchanged. Molecular dynamics simulations combined to quantum chemical methods (HF, B3LYP, B3LYP-D, M06-2X, and MP2) showed that hydrogen bonding affects the rotational barriers of TMU and TMT in markedly different ways. For TMU, the rotational barrier increases due to hydrogen bonding whereas for TMT it decreases. This behavior is a consequence of the distinct ways the ground and the transition states for rotation experience hydrogen bonding. More specifically, the ground state of TMU can form strong hydrogen bonds at the carbonyl group, which stabilize the ground state relative to the transition state. On the other hand, the sulfur of TMT showed to be a poor proton acceptor, in such a way that only the nitrogen of the twisted transition state is involved in hydrogen bonding.

Explaining and Fixing DFT Failures for Torsional Barriers

“…The accurate prediction of the torsional energy landscape of a molecule plays a crucial role in chemical and biological processes, such as estimating the selectivity of chemical reactions, − protein folding, , drug design through docking simulations, , molecular electronics, − etc. Density functional theory (DFT) calculations play an essential role in estimating the torsional energy profile ,, and also serve as a benchmark for force field parametrization in molecular dynamics simulations. ,, Standard DFT calculations using semilocal functionals and hybrids, such as B3LYP, achieve useful accuracies for the torsional profile, showing an error less than 2 kJ/mol for typical torsional barriers. − …”

Volumetric properties of some asymmetrically methyl-N-substituted thioureas in water between (278.15 and 318.15) K at ambient pressure

“…In the latter case, the differential scanning calorimeter DSC 204 F1 Phoenix was employed. The product melting point, T mp , was (392.7 ± 0.5) K for MMTU and (360.1 ± 0.5) K for 1,1,3-TMTU {the reliable literature values are (392.4 ± 0.1) K [22] and (360.6 ± 0.5) K [23], respectively}. Before and after experiments, the MMTU and TMTU samples were stored in a light-proof vacuum dessicator over P 2 O 5 .…”

Explaining and Fixing DFT Failures for Torsional Barriers

“…Density functional theory (DFT) calculations play an essential role in estimating the torsional energy profile [1,11,12] and also serve as a benchmark for force-field parameterization in molecular dynamics simulations. [16,7,8] Standard DFT calculations using semilocal functionals and hybrids such as B3LYP, [17] achieve useful accuracies for the torsional profile, showing an error of less than 2 kJ/mol for typical torsional barriers. [18,19,20] However, DFT is known to inaccurately estimate some torsional energies quantitatively and sometimes even qualitatively, particularly for π-conjugated molecules.…”