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

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 center dot center dot center dot O, C-H center dot center dot center dot N and N-H center dot center dot center dot O hydrogen bonds. Together with these hydrogen bonds, C-H center dot center dot center dot pi and C-O center dot center dot center dot pi interactions are involved in the formation of a three-dimensional crystal network. A Hirshfeld surface analysis allows the visualization of the twodimensional fingerprint plots and the quantification of the contributions of H center dot center dot center dot H, H center dot center dot center dot C/C center dot center dot center dot H and H center dot center dot center dot O/O center dot center dot center dot 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.

Automated summary

The crystal structures of three mackinazolinone derivatives were explored using X-ray crystallography, revealing the presence of various hydrogen bonds and π-π interactions in the crystal architectures, forming a three-dimensional crystal network. Hirshfeld surface analysis allows visualization of two-dimensional fingerprint plots and quantification of the contributions of different interactions.