This study investigates the hydrogen-bond geometry in six two-component solid systems composed of quinoline and chloro-nitrobenzoic acids. New X-ray diffraction studies were conducted using both the conventional independent-atom model and the more recent Hirshfeld atom-refinement method, with the latter providing precise hydrogen-atom positions. The systems can be divided into salts (the hydrogen atom transferred to the quinoline nitrogen), cocrystals (the hydrogen atom retained by the acid), and intermediate structures. Solid-state NMR experiments corroborated the X-ray diffraction-derived H-N distances. DFT calculations, using five functionals including hybrid B3LYP and PBE0, showed varying energy profiles for the hydrogen bonds, with notable differences across functionals. These calculations revealed different preferences for salt or cocrystal structures, depending on the functional used. Path-integral molecular dynamics simulations incorporating nuclear quantum effects demonstrated significant hydrogen-atom delocalization, forming a hydrogen-bond continuum, and provided average N-H distances in excellent agreement with experimental results. This comprehensive experimental and theoretical approach highlights the complexity of multicomponent solids. The study emphasizes that the classification into salts or cocrystals is frequently inadequate, as the hydrogen atom is often significantly delocalized in the hydrogen bond. This insight is crucial for understanding and predicting the behavior of such systems in pharmaceutical applications.

Department of Organic Chemistry Faculty of Science Charles University Prague 128 40 Prague 2 Czech Republic

Department of Solid State Chemistry University of Chemistry and Technology Technická 5 Praha 6 166 28 Czech Republic

Institute of Organic Chemistry and Biochemistry Czech Academy of Sciences Flemingovo nám 2 160 00 Prague 6 Czech Republic

Zobrazit více v PubMed

N. K. Duggirala, S. M. LaCasse, M. J. Zaworotko, J. F. Krzyzaniak, K. K. Arora, Cryst. Growth Des. 2020, 20, 617–626.

G. Bolla, B. Sarma, A. K. Nangia, Chem. Rev 2022, 122, 11514–11603;

S. Aitipamula, R. Banerjee, A. K. Bansal, K. Biradha, M. L. Cheney, A. R. Choudhury, G. R. Desiraju, A. G. Dikundwar, R. Dubey, N. Duggirala, P. P. Ghogale, S. Ghosh, P. K. Goswami, N. R. Goud, R. K. R. Jetti, P. Karpinski, P. Kaushik, D. Kumar, V. Kumar, B. Moulton, A. Mukherjee, G. Mukherjee, A. S. Myerson, V. Puri, A. Ramanan, T. Rajamannar, C. M. Reddy, N. Rodriguez-Hornedo, R. D. Rogers, T. N. G. Row, P. Sanphui, N. Shan, G. Shete, A. Singh, C. Q. C. Sun, J. A. Swift, R. Thaimattam, T. S. Thakur, R. K. Thaper, S. P. Thomas, S. Tothadi, V. R. Vangala, P. Vishweshwar, D. R. Weyna, M. J. Zaworotko, Cryst. Growth Des. 2012, 12, 4290–4291;

C. Y. Zhang, Y. Xiong, F. B. Jiao, M. M. Wang, H. Z. Li, Cryst. Growth Des. 2019, 19, 1471–1478.

N. Qiao, M. Z. Li, W. Schlindwein, N. Malek, A. Davies, G. Trappitt, Int. J. Pharmaceut. 2011, 419, 1–11;

M. Y. Xia, B. Q. Zhu, J. R. Wang, Z. E. Yang, X. F. Mei, ACS Med. Chem. Lett. 2022, 13, 29–37;

N. Schultheiss, A. Newman, Cryst. Growth Des. 2009, 9, 2950–2967;

C. B. Aakeröy, M. E. Fasulo, J. Desper, Molecular Pharmaceut. 2007, 4, 317–322.

European Medicines Agency, Reflection paper on the use of cocrystals of active substances in medicinal products, EMA/CHMP/CVMP/QWP/284008/2015, European Medicines Agency, 2015;

Food and Drug Administration, Regulatory Classification of Pharmaceutical Co-Crystals Guidance for Industry, U. S. Department of Health and Human Services, 2018. https://www.regulations.gov/docket/FDA-2011-D-0800

A. Kumar, S. Kumar, A. Nanda, Adv. Pharm. Bull. 2018, 8, 355–363.

E. Pindelska, A. Sokal, W. Kolodziejski, Adv. Drug Deliver. Rev. 2017, 117, 111–146;

J. R. Štoček, O. Socha, I. Císařová, T. Slanina, M. Dračínský, J. Am. Chem. Soc. 2022, 144, 7111–7116;

J. Blahut, J. R. Štoček, M. Šála, M. Dračínský, J. Magn. Reson. 2022, 345, 107334.

A. J. Cruz-Cabeza, CrystEngComm 2012, 14, 6362–6365;

A. J. Cruz-Cabeza, M. Lusi, H. P. Wheatcroft, A. D. Bond, Faraday Discuss. 2022, 235, 446–466.

S. L. Childs, G. P. Stahly, A. Park, Mol. Pharmaceutics 2007, 4, 323–338;

M. Quintano, R. T. Moura, E. Kraka, Chem. Phys. Lett. 2023, 826, 140654.

C. L. Jones, J. M. Skelton, S. C. Parker, P. R. Raithby, A. Walsh, C. C. Wilson, L. H. Thomas, CrystEngComm 2019, 21, 1626–1634.

J. S. Stevens, L. K. Newton, C. Jaye, C. A. Muryn, D. A. Fischer, S. L. M. Schroeder, Cryst. Growth Des. 2015, 15, 1776–1783.

A. S. Tatton, T. N. Pham, F. G. Vogt, D. Iuga, A. J. Edwards, S. P. Brown, Mol. Pharmaceutics 2013, 10, 999–1007;

S. L. Veinberg, K. E. Johnston, M. J. Jaroszewicz, B. M. Kispal, C. R. Mireault, T. Kobayashi, M. Pruski, R. W. Schurko, Phys. Chem. Chem. Phys. 2016, 18, 17713–17730;

S. H. Li, M. Hong, J. Am. Chem. Soc. 2011, 133, 1534–1544;

L. Zhao, M. P. Hanrahan, P. Chakravarty, A. G. DiPasquale, L. E. Sirois, K. Nagapudi, J. W. Lubach, A. J. Rossini, Cryst. Growth Des. 2018, 18, 2588–2601;

Z. J. Li, Y. Abramov, J. Bordner, J. Leonard, A. Medek, A. V. Trask, J. Am. Chem. Soc. 2006, 128, 8199–8210;

L. Rajput, M. Banik, J. R. Yarava, S. Joseph, M. K. Pandey, Y. Nishiyama, G. R. Desiraju, Iucrj 2017, 4, 466–475.

Y. Nishiyama, N. T. Duong, J. Magn. Reson. Open 2022, 10–11, 100062.

L. M. LeBlanc, S. G. Dale, C. R. Taylor, A. D. Becke, G. M. Day, E. R. Johnson, Angew. Chem. Int. Ed. 2018, 57, 14906–14910;

Y. A. Abramov, J. Wang, Cryst. Growth Des. 2024, 24, 4017–4024.

M. Hušák, S. Šajbanová, J. Klimeš, A. Jegorov, Acta Cryst. B 2022, 78, 781–788.

K. Gotoh, H. Ishida, Acta Crystallogr. C 2009, 65, O534–O538;

K. Gotoh, H. Ishida, Acta Crystallogr. E 2011, 67, O2883.

C. R. Groom, I. J. Bruno, M. P. Lightfoot, S. C. Ward, Acta Crystallogr., Sect. B 2016, 72, 171–179.

V. Šolínová, V. Kašička, Electrophoresis 2013, 34, 2655–2665.

R. Williams, pKa Values in Water Compilation, 2022. https://organicchemistrydata.org/hansreich/resources/pka/.

F. Kleemiss, O. V. Dolomanov, M. Bodensteiner, N. Peyerimhoff, L. Midgley, L. J. Bourhis, A. Genoni, L. A. Malaspina, D. Jayatilaka, J. L. Spencer, F. White, B. Grundkötter-Stock, S. Steinhauer, D. Lentz, H. Puschmann, S. Grabowsky, Chem. Sci. 2021, 12, 1675–1692.

S. C. Capelli, H. B. Bürgi, B. Dittrich, S. Grabowsky, D. Jayatilaka, IUCrJ 2014, 1, 361–379;

M. Woińska, D. Jayatilaka, M. A. Spackman, A. J. Edwards, P. M. Dominiak, K. Woźniak, E. Nishibori, K. Sugimoto, S. Grabowsky, Acta Cryst. A 2014, 70, 483–498;

H. Puschmann, O. Dolomanov, Acta Cryst. A 2018, 74, E40–E40.

N. T. Duong, F. Rossi, M. Makrinich, A. Goldbourt, M. R. Chierotti, R. Gobetto, Y. Nishiyama, J. Magn. Reson. 2019, 308, 106559.

L. Chen, Q. A. Wang, B. W. Hu, O. Lafon, J. Trébosc, F. Deng, J. P. Amoureux, Phys. Chem. Chem. Phys. 2010, 12, 9395–9405.

R. Pohl, O. Socha, P. Slavíček, M. Šála, P. Hodgkinson, M. Dračínský, Faraday Discuss 2018, 212, 331–344.

O. V. Dolomanov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard, H. Puschmann, J. Appl. Cryst. 2009, 42, 339–341.

F. Neese, WIREs Computat. Mol. Sci. 2022, 12, e1606.

A. Bielecki, D. P. Burum, J. Magn. Reson. A 1995, 116, 215–220.

D. G. Cory, W. M. Ritchey, J. Magn. Reson. 1988, 80, 128–132.

B. Tatman, H. Modha, S. P. Brown, J. Magn. Reson. 2023, 352, 107459;

M. H. Levitt, Encycl. Magn. Reson. 2007, 2007, 229.

X. B. Lou, M. Shen, C. Li, Q. Chen, B. W. Hu, Solid State Nucl. Magn. Reson. 2018, 94, 20–25.

F. Pourpoint, J. Trébosc, R. M. Gauvin, Q. Wang, O. Lafon, F. Deng, J. P. Amoureux, ChemPhysChem 2012, 13, 3605–3615.

S. J. Clark, M. D. Segall, C. J. Pickard, P. J. Hasnip, M. J. Probert, K. Refson, M. C. Payne, Z. Kristallogr. 2005, 220, 567–570.

F. H. Allen, Acta Cryst. B 2002, 58, 380–388.

J. P. Perdew, K. Burke, M. Ernzerhof, Phys. Rev. Lett. 1996, 77, 3865–3868.

A. P. Bartók, J. R. Yates, J. Chem. Phys. 2019, 150, 161101.

J. W. Furness, A. D. Kaplan, J. L. Ning, J. P. Perdew, J. W. Sun, J. Phys. Chem. Lett. 2020, 11, 8208–8215.

A. D. Becke, J. Chem. Phys. 1993, 98, 5648–5652;

C. T. Lee, W. T. Yang, R. G. Parr, Phys. Rev. B 1988, 37, 785–789.

C. Adamo, V. Barone, J. Chem. Phys. 1999, 110, 6158–6170.

D. Vanderbilt, Phys. Rev. B 1990, 41, 7892–7895.

H. J. Monkhorst, J. D. Pack, Phys. Rev. B 1976, 13, 5188–5192.

A. Tkatchenko, M. Scheffler, Phys. Rev. Lett. 2009, 102, 073005.

A. Tkatchenko, R. A. DiStasio, R. Car, M. Scheffler, Phys. Rev. Lett. 2012, 108, 236402.

E. Caldeweyher, S. Ehlert, A. Hansen, H. Neugebauer, S. Spicher, C. Bannwarth, S. Grimme, J. Chem. Phys. 2019, 150, 154122.

M. Dračínský, P. Bouř, P. Hodgkinson, J. Chem. Theory Comput. 2016, 12, 968–973.

M. Dračínský, P. Hodgkinson, Chem. Eur. J. 2014, 20, 2201–2207.

T. Higashi, ABSCOR, Program for Absorption Correction. Rigaku Corporation, Tokyo, 1995;

G. M. Sheldrick, SADABS: Program for Empirical Absorption Correction of Area Detector Data, University of Göttingen, 1996;

PROCESS-AUTO (Rigaku/MSC, 2004), 2004;

CrystalStructure (Rigaku/MSC, 2004), 2004;

G. M. Sheldrick, SHELXL97. Program for Crystal Structure Refinement from Diffraction Data, University of Göttingen, Göttingen, 1997;

L. J. Bourhis, O. V. Dolomanov, R. J. Gildea, J. A. K. Howard, H. Puschmann, Acta Crystallogr. A 2015, 71, 59–75;

T. Higashi, Absorption Correction: Numerical, NUMABS, 1999.

Deposition Number(s) href=https://www.ccdc.cam.ac.uk/services/structures?id=doi:10.1002/chem.2024029462365049 (for AJIWIA), 2365050 (for AJIWOG), 2365051 (for AJIWUM), 2365052 (for AJIXAT), 2365053 (for AJIXAT-new) and 2365048 (for YAGFAP) contain(s) the supplementary crystallographic data for this paper. These data are provided free of charge by the joint Cambridge Crystallographic Data Centre and Fachinformationszentrum Karlsruhe href=“http://www.ccdc.cam.ac.uk/structures” Access Structures service.

Computation screening for incorrectly determined cocrystal structures

Striking Impact of Solvent Polarity on the Strength of Hydrogen-Bonded Complexes: A Nexus Between Theory and Experiment