Structural insight from intermolecular interactions and energy framework analyses of 2-substituted 6,7,8,9-tetrahydro-11H-pyrido[2,1-b]quinazolin-11-ones

Abstract

The crystal structures of three mackinazolinone derivatives (2-amino-6,7,8,9-tetrahydro-11H-pyrido[2,1-b]quinazolin-11-one at room temperature, and 2-nitro-6,7,8,9-tetrahydro-11H-pyrido[2,1-b]quinazolin-11-one and N-(11-oxo-6,8,9,11-tetrahydro-7H-pyrido[2,1-b]quinazolin-2-yl)benzamide at 100 K) are explored using X-ray crystallography. To delineate the different intermolecular interactions and the respective interaction energies in the crystal architectures, energy framework analyses were carried out using the CE-B3LYP/6-31G(d,p) method implemented in the CrystalExplorer software. In the structures the different molecules are linked by C—H...O, C—H...N and N—H...O hydrogen bonds. Together with these hydrogen bonds, C—H...π and C—O...π interactions are involved in the formation of a three-dimensional crystal network. A Hirshfeld surface analysis allows the visualization of the two-dimensional fingerprint plots and the quantification of the contributions of H...H, H...C/C...H and H...O/O...H contacts throughout the different crystal structures. To obtain additional information on the intrinsic properties of our targets and to compare the experimental crystal structures with their respective conformations in the gas phase, quantum chemical calculations at the B3LYP-D3BJ/6-311++G(d,p) level of theory, including Grimme's D3 correction term and BJ damping functions, were carried out to account for intramolecular dispersion interactions. The identified energy gaps between the highest occupied and the lowest unoccupied molecular orbitals (HOMO–LUMO gap) of our targets in the gas phase and in two implicit solvents (methanol and dimethyl sulfoxide) allow us to quantify the impact of different substituents on the reactivity of mackinazolinone derivatives.

Quantitative Analysis the Weak Non-Covalent Interactions of the Polymorphs of Donepezil

“…The scale factor in the energy framework is 200, and the interaction energy less than 5 kJ/mol is ignored. 19 The CLP-PIXEL software package can be used to calculate the lattice energy of AA-CLP. The intermolecular potential energy in the crystal was calculated using the following equation (eq 1):…”

“…The energy frameworks can perform energy framework analysis of intermolecules in the 3.8 Å range of donepezil. The scale factor in the energy framework is 200, and the interaction energy less than 5 kJ/mol is ignored . The CLP-PIXEL software package can be used to calculate the lattice energy of AA-CLP.…”

“…The scale factor in the energy framework is 200, and the interaction energy less than 5 kJ/mol is ignored. 19 The CLP-PIXEL software package can be used to calculate the lattice energy of AA-CLP. The intermolecular potential energy in the crystal was calculated using the following equation ( eq 1 ): where R ij is the intermolecular distance between nuclear positions, A, B, and C are the empirical parameters, and q i is the atomic charge parameter at the nuclear positions.…”