Scheme 2 Individual sequences simulated in this study; (a)
substitution by an amine nucleophile (b) elimination of water to form
the imine and (c) deprotonation.
All calculations were performed using DFT method implemented in the
Gaussian G09. [59] All structures
were optimized using hybrid meta exchange-correlation functionals,
M06-2X with a 6-311+G(d,p) basis
set.[60,
61] The reaction mechanism associated
with SB formation was studied in the gasphase following the mechanism
described in Scheme 2. In this model, a methylamine molecule acts as
both the nucleophile and base in the reaction. Two explicitly modelled
water molecules provide additional stabilization and facilitate proton
transfer steps. The vibrational frequency calculations were performed to
confirm all transition states (TS). TSs are characterized by having a
single imaginary frequency and minima having none. The rate determining
barrier were subsequently determined. Additional substrate properties
(MWT and clogP) were obtained using the Chemaxon
JChem.[62]
The correlation between independent and dependent variables was assessed
using linear regression. The data was partitioned into a training (M=14)
and test set (N=8) and a QMM was fitted using the RDS barrier and the
logP using multiple linear regression. All statistical analyses were
performed in Statistica 12.[63]