A Computational Study of Microhydrated N-Acetyl-Phenylalaninylamide (NAPA): Kinetics and Thermodynamics

Abstract

The formations of [NAPA-A(H 2 O) n (n = 1, 2, 3, 4)] complexes have been studied employing DFT/wB97XD/cc-pVTZ computational level to understand the kinetics and thermodynamics for the hydration reactions of N-acetylphenylalaninylamide (NAPA). Thermodynamic parameters such as reaction energy (E), enthalpy (H), Gibb's free energy (G), specific heat capacity (C v ), entropy (S), and change of these parameters (ΔE r , ΔH r , ΔG r , ΔC r, and ΔS r ) were studied using the explicit solvent model. The predicted values of H, G, C, and S increase with the sequential addition of water in NAPA-A due to the increase in the total number of vibrational modes. On the other hand, the value of ΔE r , ΔH r, and ΔG r increases (more negative to less negative) gradually for n = 1, 2, 3, and 4 that indicates an increase of hydration in NAPA-A makes exothermic to endothermic reactions. The barrier heights for the transition states (TS) of [NAPA-A(H 2 O) n (n = 1, 2, 3, 4)] complexes are predicted to lie at 4.41, 4.05, 3.72 and 2.26 kcal/mol respectively below the reactants. According to the calculations, the formations of [NAPA-A(H 2 O) 1 ] and [NAPA-A(H 2 O) 2 ] complexes are barrierless reactions because both water molecules are strongly bonded via two hydrogen bonds in the backbone of NAPA-A. On the contrary, the reactions of [NAPA-A(H 2 O) 3 ] and [NAPA-A(H 2 O) 4 ] complexation are endothermic and the barrier heights are predicted to stay at 6.30 and 10.54 kcal/mol respectively above the reactants. The free energy of activation (Δ ‡ G 0 ) for the reaction of [NAPA-A(H 2 O) 1 ], [NAPA-A(H 2 O) 2 ], [NAPA-A(H 2 O) 3 ], and [NAPA-A(H 2 O) 4 ] complexation are 4 .43, 4.28, 3.83 and 5.11 kcal/mol respectively which are very low. As well as the rates of reactions are 3.490 × 10 9 s −1 , 4.514 × 10 9 s −1 , 9.688 × 10 9 s −1 , and 1.108 × 10 9 s −1 respectively which are very fast and spontaneous.