2 research outputs found
Combined Experimental and Computational Studies of Pyrazinamide and Nicotinamide in the Context of Crystal Engineering and Thermodynamics
Pyrazinamide and nicotinamide constitute
small, rigid molecules,
which are of importance in several areas of science, including crystal
engineering, chemical synthesis, biochemistry, and pharmacy. This
contribution is dedicated to the comprehensive study of experimental
charge density distributions and computational analysis of the β
form of pyrazinamide and α form of nicotinamide. Static electron
density distribution is obtained through application of Hansen and
Coppens multipolar formalism, and further analyzed via Bader’s
quantum theory of atoms in molecules (QTAIM). Geometrical and electron
density features of both crystals, such as atomic charges, bond critical
points, electrostatic potential and experimentally derived intermolecular
interactions are described and compared. The presence of the additional
nitrogen atom in the aromatic ring of pyrazinamide, when compared
to nicotinamide, has, as expected, a major influence on the surrounding
atoms, including the amide moiety (0.2 e difference on the carbonyl
group carbon atom). This, in consequence, affects the electrostatic
potential in this region, and thus the favorable weak interactions
of both molecules, what leads to the substantially different crystal
packing motifs. These considerations were quantified in terms of computational
methods (periodic DFT and PIXEL approaches), resulting in the conclusion
of the α form of nicotinamide crystal being more energetically
advantageous. Additionally, a proper deconvolution of thermal motion
from static charge density provides precise and accurate atomic displacement
parameters (ADPs). This allows for estimation of vibrational entropy
contribution to the total stabilization of the studied crystal structures
by means of Madsen and Larsen approach. It appeared that vibrational
entropies obtained by employing ADPs after full multipolar refinement
on high-resolution data are in good agreement with the corresponding
values derived from ADPs after the transferred aspherical atom model
(TAAM) refinement performed on the low-resolution data. This comparison,
conducted here for the very first time, opens up the possibility of
routine entropy evaluation for various crystal structures using multipole
parameter databanks
Superarming of Glycosyl Donors by Combined Neighboring and Conformational Effects
A novel glycosyl donor that combines the concepts of both conformational and electronic superarming has been synthesized. The reactivity and selectivity of the donor have been tested in competition experiments