Influence of N-protonation on electronic properties of acridine derivatives by quantum crystallography.

Autor:	Pawlędzio S; Neutron Scattering Division, Oak Ridge National Laboratory Oak Ridge TN 37831 USA pawledzios@ornl.gov.; Department of Chemistry, Biological and Chemical Research Centre, University of Warsaw Żwirki i Wigury 101 02-093 Warszawa Poland kwozniak@chem.uw.edu.pl., Ziemniak M; Department of Chemistry, Biological and Chemical Research Centre, University of Warsaw Żwirki i Wigury 101 02-093 Warszawa Poland kwozniak@chem.uw.edu.pl., Trzybiński D; Department of Chemistry, Biological and Chemical Research Centre, University of Warsaw Żwirki i Wigury 101 02-093 Warszawa Poland kwozniak@chem.uw.edu.pl., Arhangelskis M; Department of Chemistry, Biological and Chemical Research Centre, University of Warsaw Żwirki i Wigury 101 02-093 Warszawa Poland kwozniak@chem.uw.edu.pl., Makal A; Department of Chemistry, Biological and Chemical Research Centre, University of Warsaw Żwirki i Wigury 101 02-093 Warszawa Poland kwozniak@chem.uw.edu.pl., Woźniak K; Department of Chemistry, Biological and Chemical Research Centre, University of Warsaw Żwirki i Wigury 101 02-093 Warszawa Poland kwozniak@chem.uw.edu.pl.
Jazyk:	angličtina
Zdroj:	RSC advances [RSC Adv] 2024 Feb 12; Vol. 14 (8), pp. 5340-5350. Date of Electronic Publication: 2024 Feb 12 (Print Publication: 2024).
DOI:	10.1039/d3ra08081a
Abstrakt:	Applications of 9-aminoacridine (9aa) and its derivatives span fields such as chemistry, biology, and medicine, including anticancer and antimicrobial activities. Protonation of such molecules can alter their bioavailability as weakly basic drugs like aminoacridines exhibit reduced solubility at high pH levels potentially limiting their effectiveness in patients with elevated gastric pH. In this study, we analyse the influence of protonation on the electronic characteristics of the molecular organic crystals of 9-aminoacridine. The application of quantum crystallography, including aspherical atom refinement, has enriched the depiction of electron density in the studied systems and non-covalent interactions, providing more details than previous studies. Our experimental results, combined with a topological analysis of the electron density and its Laplacian, provided detailed descriptions of how protonation changes the electron density distribution around the amine group and water molecule, concurrently decreasing the electron density at bond critical points of N/O-H bonds. Protonation also alters the molecular architecture of the systems under investigation. This is reflected in different proportions of the N⋯H and O⋯H intermolecular contacts for the neutral and protonated forms. Periodic DFT calculations of the cohesive energies of the crystal lattice, as well as computed interaction energies between molecules in the crystal, confirm that protonation stabilises the crystal structure due to a positive synergy between strong halogen and hydrogen bonds. Our findings highlight the potential of quantum crystallography in predicting crystal structure properties and point to its possible applications in developing new formulations for poorly soluble drugs. Competing Interests: There are no conflicts of interest to declare. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
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