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Hirshfeld surface analysis and energy framework for crystals of quinazoline methylidene bridged compounds
* 1 , 2, 3 , 4 , 4 , 4 , 2 , 2, 5 , 2
1  Arifov Institute of Ion-Plasma and Laser Technologies, Academy of Sciences of Uzbekistan
2  S.Yunusov Institute of Chemistry of Plant Substances, Academy of Sciences of Uzbekistan, Mirzo Ulugbek Str. 77, 100170 Tashkent, Uzbekistan
3  National University of Uzbekistan named after Mirzo Ulugbek, 100174 University str 4 Olmazor district Tashkent, Uzbekistan
4  Institute of Inorganic Chemistry, RWTH Aachen University, Landoltweg 1, 52056, Aachen, Germany
5  Turin Polytechnic University in Tashkent, Kichik Khalka yuli str., 17, 100095 Tashkent, Uzbekistan

Published: 05 November 2020 by MDPI in The 2nd International Online Conference on Crystals session Crystal Engineering

Among the drugs used worldwide, 50-60% are isolated or produced from plants; about half of these drugs are alkaloids or nitrogen-containing compounds. Within the alkaloids, quinazoline derivatives are of particular interest as they have a wide range of biological activity [1,2]. Their versatility stimulates the synthesis of new compounds containing the quinazoline fragment, with the aim of even increased biological activity. Continuing our research in this direction [3], the crystal structures of 3- (3,4-dimethoxyphenylethylamino)-methylidene-1,2,3,9-tetrahydropyrrolo [2,1-b] quinazolin-9-one (1) and 4-(3,4-dimethoxyphenylethylamino)-methylidene-2,3,4,10-tetrahydro-1H-pyrido [2,1-b] -quinazolin-10-one (2) were studied. The structures of compounds 1 and 2 were established by single crystal X-ray diffraction. Their molecular and crystal structures were described in the context of intra and inter-molecular interactions and of stereoisomerism.

For molecular crystals, Hirshfeld surface analyses may provide insight into intermolecular interactions, and energy framework analyses allow to quantify different contributions to the overall energy. These analyses were performed to pinpoint intermolecular interactions in 1 and 2. According to our results, the molecules are associated by intra- and intermolecular hydrogen bonds, C—H···π and C—O···π stacking interactions. The three-dimensional Hirshfeld surface analysis and two-dimensional fingerprint plots revealed that the structures are dominated by H···H, H···C/C···H and H···O/O···H contacts. The intermolecular energy analysis revealed a significant contribution of electrostatic and dispersion components for the stabilization of molecular packing.

Keywords: crystal structure; quinazoline; intermolecular interaction energy
Comments on this paper
Catherine Raptopoulou
I have read this very interesting paper. There are some issues that need the attention of the authors. Most of them are typos and these are: 1) line 66: the crystals of (2) were very small; 2) lines 105 and 142: numbers of the structures should be in bold; 3) line 136: missing bonds, please fill with dotted lines; 4) line 143: please define which structure the description is related to. The quality of the figures 1(a, b), 2(a,b) and 3(a,b) is very poor. Please provide figures of higher quality. In the conclusions part, please add comments for structure 2.
Akmaljon Tojiboev
Dear Catherine Raptopoulou,

Thank you very much for your comments. I updated the paper corrected to your comments.

Best wishes
Akmal Tojiboev

Paola Paoli
XRD data and Hirshfeld surface analysis
The paper nicely shows how single crystal X-ray data and the Hirshfeld surface analysis complement each other to fully characterize the crystal packing.
Akmaljon Tojiboev
Thank you very much

Jesus Sanmartín-Matalobos
hydrogen bonds N - H ∙∙∙ N
The study of the stabilization of the Z and E isomers has piqued my interest. The stabilization of the Z isomer by intramolecular N-H∙∙∙ O hydrogen bonds is agree with that expected. However, I cannot see the stabilization of
the E isomer by intramolecular hydrogen bonds N - H ∙∙∙ N, as indicated in conclusions section. This is probably a mistake, and the hydrogen bonds N - H ∙∙∙ N are actually intermolecular interactions.
Akmaljon Tojiboev
Dear Jesus Sanmartín-Matalobos,

Thank you very much for your comments.

The paper of version on 16 November 2020, in the text N—H∙∙∙O intermolecular hydrogen bonds which are responsible for E configuration were mentioned (line 118 and line 127). In conclusion, was a mistake with the typo "intramolecular" (line 202). I updated the paper with the correction to the "intermolecular".

Best wishes
Akmal Tojiboev

Jesus Sanmartín-Matalobos
Thanks for your answer.
Best wishes