Next Article in Journal
Biomedical Sensing with Free-Standing Complementary Supercell Terahertz Metasurfaces
Next Article in Special Issue
Design, Synthesis, Crystal Structure, and Fungicidal Activity of Two Fenclorim Derivatives
Previous Article in Journal
X-ray Induced Hydroxyl Radical Generation by GdYVO4:Eu3+ Nanoparticles in Aqueous Solution: Main Mechanisms
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Crystals
Volume 10
Issue 5
10.3390/cryst10050371
crystals-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

New Crystal Forms for Biologically Active Compounds. Part 2: Anastrozole as N-Substituted 1,2,4-Triazole in Halogen Bonding and Lp-π Interactions with 1,4-Diiodotetrafluorobenzene

by
Mariya A. Kryukova
,
Alexander V. Sapegin
,
Alexander S. Novikov
,
Mikhail Krasavin
and
Daniil M. Ivanov
*
Institute of Chemistry, Saint Petersburg State University, Universitetskaya Nab. 7/9, 199034 Saint Petersburg, Russia
*
Author to whom correspondence should be addressed.
Crystals 2020, 10(5), 371; https://doi.org/10.3390/cryst10050371
Submission received: 28 March 2020 / Revised: 1 May 2020 / Accepted: 2 May 2020 / Published: 5 May 2020
(This article belongs to the Special Issue Pharmaceutical Crystals (Volume II))
Browse Figures
Versions Notes

Abstract

:
For an active pharmaceutical ingredient, it is important to stabilize its specific crystal polymorph. If the potential interconversion of various polymorphs is not carefully controlled, it may lead to deterioration of the drug’s physicochemical profile and, ultimately, its therapeutic efficacy. The desired polymorph stabilization can be achieved via co-crystallization with appropriate crystallophoric excipients. In this work, we identified an opportunity for co-crystallization of anastrozole (ASZ), a well-known aromatase inhibitor useful in second-line therapy of estrogen-dependent breast cancer, with a classical XB donor, 1,2,4,5-tetrafluoro-3,6-diiodobenzene (1,4-FIB). In the X-ray structures of ASZ·1.5 (1,4-FIB) co-crystal, different non-covalent interactions involving hydrogen and halogen atoms were detected and studied by quantum chemical calculations and QTAIM analysis at the ωB97XD/DZP-DKH level of theory.

Graphical Abstract

1. Introduction

The generation of a new salt form is a proven way to modify the physical and chemical properties of an active pharmaceutical ingredient (API) [1]. To be able to give rise to a new salt form, however, the API in question should be ionizable. For non-ionizable APIs, co-crystallization with a crystallophoric excipient (non-API component of the solid drug form) has become an alternative, proven way of accessing a broad range of solid forms and thus modifying various physicochemical properties and increasing API’s stability [2,3,4]. An overwhelming majority of API co-crystals reported today are based on hydrogen bonding as the principal means of constructing the crystalline form. However, halogen bonds have emerged as an equally promising basis for designing new co-crystalline API forms [5,6,7,8,9,10,11,12]. However, despite the emergence of this intriguing supramolecular interaction, halogen-bonded API co-crystals remain relatively scarce. This may have to do with the limited range of pharmaceutically acceptable excipients containing polarized halogen atoms [13]. In continuation of our efforts to identify new crystalline forms for APIs that would be stabilized by halogen bonding [14,15], we turned our attention to screening of crystallization conditions for the title compound, anastrozole (IUPAC name 2,2′-(5-((1H-1,2,4-triazol-1-yl)methyl)-1,3-phenylene)bis(2-methylpropanenitrile), abbreviated as ASZ), which is an aromatase inhibitor useful in second-line therapy of estrogen-dependent breast cancer [16,17,18].
We choose this API as a potential recipient of XB due to its 1,2,4-triazole moiety, containing at least two nucleophilic Nsp2 atoms as potential XB acceptor centers. One of them is a hydrogen bond [19] (HB) acceptor in the crystal structure of ASZ itself (Figure 1) [20].
Previously, we successfully cocrystallized another API, nevirapine, with classic XB donor, 1,2,4,5-tetrafluoro-3,6-diiodobenzene (also known as 1,4-diiodotetrafluorobenzene, 1,4-FIB). Noticeably, 1,4-FIB has already been employed in the co-crystal formation for a number of biologically active compounds including nicotine [21], pyrazinamide, lidocaine, and pentoxifylline [22]. It should be noted, however, that in these studies (as well as in present work), 1,4-FIB is employed as an exploratory co-crystallization partner. For its use as an excipient for the design of solid drug forms, a further clinical investigation will be required. In this work, we found ASZ can also be cocrystallized with 1,4-FIB from their solution in MeOH, forming the 2:3 adduct. Herein, we present the results of combined single-crystal XRD experimental and theoretical studies of the adduct and noncovalent interactions found in it.

2. Materials and Methods

2.1. Materials

Anastrozole, 1,2,4,5-tetrafluoro-3,6-diiodobenzene, and MeOH were obtained from a commercial source and used as received.

2.2. X-ray Structure Determination

Crystal of ASZ·1.5(1,4-FIB) was investigated on an Xcalibur, Eos diffractometer at 100 K (monochromated MoKα radiation with λ = 0.71073 Å). The structure was solved by the direct methods (SHELX program [23]) in the OLEX2 program package [24]. The carbon-bound H atom positions were calculated and included in the refinement in the ‘riding’ model approximation. Uiso(H) were set to 1.5Ueq(C) (for CH3 groups) or 1.2Ueq(C) (for CH2 and CH groups). The C–H bond lengths are 0.98 Å for CH3 groups, 0.99 Å for CH2 groups, and 0.95 Å for CH groups. Empirical absorption correction was applied in the CrysAlisPro [25] program. For crystallographic data and refinement parameters see Supplementary material (Table S3). Supplementary crystallographic data was deposited at Cambridge Crystallographic Data Centre (CCDC 1960975) and can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif.

2.3. Powder X-ray Diffraction Experiments

The X-ray diffraction of powder samples was measured at room temperature on a D8 Discover high-resolution diffractometer using monochromated CuKα (λ = 1.54184 Å) radiation.

2.4. Computational Details

The single point calculations based on the experimental X-ray geometry of (ASZ)3·(1,4-FIB)4 have been carried out at the DFT level of theory using the dispersion-corrected hybrid functional ωB97XD [26] with the help of the Gaussian-09 [27] program package. The Douglas–Kroll–Hess 2nd order scalar relativistic calculations requested relativistic core Hamiltonian were carried out using the DZP-DKH basis sets [28,29,30,31] for all atoms. The topological analysis of the electron density distribution with the help of the atoms in molecules (QTAIM) method developed by Bader [32] has been performed by using the Multiwfn program [33]. The Cartesian atomic coordinates of a model supramolecular cluster are presented in Supporting Information, Table S4.

3. Results and Discussion

3.1. Halogen Bonding in ASZ·1.5(1,4-FIB)

Slow evaporation of a MeOH solution of ASZ with 1,4-FIB taken in a 1:1 ratio leads to the formation on single crystals of ASZ·1.5(1,4-FIB) suitable for the X-ray diffraction experiment. It is notable that we also tried to synthesize the ASZ·1.5(1,4-FIB) pure phase both by mechanical grinding of 2:3 ASZ + 1,4-FIB mixture with MeOH additions during the process or by crystallization of the same 2:3 mixture from methanol with the following grinding of obtained crystalline material. Powder X-ray diffraction experiments for both cases show that ASZ·1.5(1,4-FIB) coexists with some other unidentified phases (see Figures S3 and S4 in SI). For details on the powder x-ray diffraction experiments see also Section 2.3.
According to the single-crystal XRD data, the cocrystallization of ASZ with 1,4-FIB does not lead to any relevant changes, considering the 3σ criterion, in covalent bond lengths of ASZ [20] and 1,4-FIB [34].
As expected, the C–I⋯N contacts were found in ASZ·1.5(1,4-FIB) (Figure 2), which can be interpreted as halogen bonding [35]. In accordance with their geometrical parameters (Table 1), the theoretically estimated energies of these contacts are 4.6–5.3 kcal/mol (I3S⋯N2) and 4.8–6.0 kcal/mol (I1S⋯N3), which is comparable with a lower limit for strength of “moderate” hydrogen bonding according to Jeffrey’s classification (“strong”: 40−15 kcal/mol; “moderate”: 15−4 kcal/mol; “weak”: <4 kcal/mol) [36]. For 1,4-FIB, the molecular electrostatic potential calculations were reported [37,38,39], which confirm the σ-hole electrophilicity [40,41] of iodine atoms in this molecule.
Previously, the C–I⋯N XBs including 1,2,4-triazole moiety was mentioned only in two metal-organic frameworks (FALNEN [43] and UMOTOG [44]) and one free 4H-1,2,4-triazole (FARCIN01 [45]). We analyzed all the structures containing the C–I⋯N XBs with 1,2,4-triazoles in CCDC and found 9 more structures [44,46,47,48,49,50,51,52]. It is notable that in all corresponding works, these interactions were not even mentioned. The I⋯N distances are in the range of 2.839 (4)–3.378 (3) Å, and the ∠(C–I⋯N) angles vary from 157.18 (17) to 177.57 (8)° (for details see Table S1 in supplementary materials). In ASZ·1.5 (1,4-FIB), both distances (2.883 (7) and 2.913 (6) Å) are shorter than in most previously published structures, which can be explained by the electron-withdrawing I substituent in 1,4-FIB. Noticeably, the C–Cl⋯N [53,54,55] and C–Br⋯N [45,53,56,57,58] XBs including 1,2,4-triazole moiety are also mentioned in the literature.
Halogen bonding was also found between 1,4-FIB molecules, represented by bifurcated C–I⋯(I,F) contact (Figure 3). Both distances are less than vdW sums, and both angles are around 150° (Table 1) and fall into an acceptable value for XBs. These non-covalent interactions are weak, viz. 1.3 kcal/mol in the case of I2S⋯F6S and 1.6 kcal/mol in the case of I2S⋯I3S.
A resembling feature can be found in the structure KUWRAX [59], where both I⋯F and I⋯I distances are less than the corresponding vdW sums (3.6889 (7) vs 3.96 Å and 3.409 (3) vs 3.45 Å), however, in this structure, the corresponding ∠(C–I⋯F) angle (125.09 (13)°) is not high enough to recognize this interaction as halogen bonding. Thus, ASZ·1.5(1,4-FIB) demonstrates the first example of bifurcated C–I⋯(I,F) halogen bonding between 1,4-FIB molecules.

3.2. Lone-Pair∙∙∙π Interactions in ASZ·1.5(1,4-FIB)

Besides the expected C–I⋯N halogen bonding, the C⋯I–C contacts (Table 2) were identified between ASZ and 1,4-FIB molecules in ASZ·1.5 (1,4-FIB) (Figure 4). According to the ∠(C⋯I–C) angle, which is close to 90° (Table 2), this interaction can be interpreted as lp(I)⋯π(C) interaction [60]. Their theoretically estimated strength is 1.6 kcal/mol.
Previously, the lp(I)⋯π(C) interactions including 1,2,4-triazole moiety were discussed only for five 1,2,4-triazolium iodides [61,62], where these interactions are interionic. We analyzed the CCDC data and identified 23 more structures with the C⋯I interactions including 1,2,4-triazoles. 1,2,4-triazolium iodides [20,63,64,65,66,67,68,69,70] were also found in 15 structures. The C⋯I–M interactions [71,72,73,74,75,76] in 1,2,4-triazole-containing MOFs were detected in 6 structures. Structure XIWGOC contains the C⋯I− interactions between the cationic IrIII complex and iodide counterion [77]. Only in the IDIFEH structure was another example of the C⋯I–C interactions between neutral isolated molecules [78] identified. The C⋯I distances vary from 3.4363(2) to 3.670 (3) Å (for details see Table S2), and the C9⋯I1S distance (3.528 (8) Å) in ASZ·1.5(1,4-FIB) is within this range.
Besides, possible lp(I)⋯π(C) interaction between 1,4-FIB molecules was found (Figure 5). Although the C⋯I distance is around the vdW sum (3.686 (8) vs 3.68 Å), further theoretical calculations performed on experimentally determined atomic coordinates (see next section) confirmed the existence of the interaction and its noncovalent nature (estimated energy is 0.9–1.1 kcal/mol). Notably, the same interactions were found by us for 1,4-FIB and other iodofluorobenzenes [60,79,80].

3.3. Hydrogen Bonding in ASZ·1.5(1,4-FIB)

As well as in the structure of free ASZ, cyano N atoms are involved in weak hydrogen bonding (theoretically estimated strength of appropriate contacts vary from 0.9 to 1.9 kcal/mol) (Figure 6 and Table 3). Apart from methyl H atoms, the hydrogen atom in the methylene group is also an HB donor, which was not observed in the ASZ structure previously.

3.4. Theoretical Study of Different Non-covalent Interactions in ASZ·1.5(1,4-FIB)

The supramolecular structure of ASZ·1.5(1,4-FIB) is formed by various non-covalent contacts (viz. lp-π interactions, hydrogen, and halogen bonding). We performed quantum chemical calculations and QTAIM analysis [32] to study the nature and energies of these non-covalent contacts in a model supramolecular cluster (ASZ)3·(1,4-FIB)4 based on the appropriate X-ray diffraction data (Supporting Information, Table S4). This approach depends very slightly on the basis set [81,82] or method [83,84] used and it was already successfully used by us previously for similar chemical systems [14,15,79,85,86] and upon studies of different non-covalent interactions (e.g., hydrogen/chalcogen/halogen bonds, stacking interactions, metallophilic interactions) in other organic and inorganic compounds [14,15,87,88,89,90,91,92]. The results of QTAIM analysis are presented in Table 4 and visualized in Figure 7.
The QTAIM analysis reveals the existence of bond critical points (3, −1) (BCPs) for all non-covalent interactions listed in Table 4. The properties of electron density, Laplacian of electron density and energy density in these BCPs are common for non-covalent interactions. Energies for these non-covalent contacts (vary from 0.9 to 6.0 kcal/mol) were defined according to the procedures developed by Espinosa et al. [93] and Vener et al. [94] using the equations Eint = 0.5(−V(r)) or Eint = 0.429G(r), respectively. The balance between the potential energy density V(r) and Lagrangian kinetic energy G(r) at the BCPs reveals that a covalent contribution is absent in all supramolecular contacts listed in Table 4, except I1S⋯N3 halogen bonding [96].

4. Conclusions

In combination with 1,2,4,5-tetrafluoro-3,6-diiodobenzene, a classical XB donor, we have identified a new halogen-bonded solid for anastrozole, an anticancer aromatase inhibitor drug. These findings continue to provide proof-of-principle for the productive employment of halogen bonds in the design and discovery of stable crystalline forms of important drug substances. Moreover, these results suggest that the range of potential XB donors for co-crystallization with basic nitrogen-rich molecular frameworks can potentially be expanded beyond the classical ones. The distinctive features of the crystal structures obtained and characterized in detail in this work are the presence of XBs with both triazole N atoms, firstly found for anastrazole. Apart from that, the adduct structure demonstrates the lp(I)⋯π(triazole) attractive interactions, which may also be important for the adduct formation. The findings encourage us to continue searching for yet novel opportunities to detect XBs as indispensable forces leading to the formation of a new crystal. The results of these studies will be reported in due course.

Supplementary Materials

The following are available online at https://www.mdpi.com/2073-4352/10/5/371/s1, Figure S1: Structural motifs around the C–I⋯N XBs including 1,2,4-triazole moiety in CCDC structures; Figure S2: Structural motifs around the lp(I)⋯C interactions including 1,2,4-triazole moiety in CCDC structures; Figure S3: Powder X-ray diffraction data (blue line) of mixture, obtained by mechanical grinding of 2ASZ + 3(1,4-FIB) mixture with MeOH additions; Figure S4: Powder X-ray diffraction data (blue line) of mixture, obtained by grinding of crystalline material grown from 2ASZ + 3(1,4-FIB) solution in methanol; Table S1: Parameters of the C–I⋯N XBs including 1,2,4-triazole moiety in CCDC structures; Table S2: Parameters of the lp(I)⋯C interactions including 1,2,4-triazole moiety in CCDC structures; Table S3: Crystal data and structure refinement for ASZ·1.5(1,4-FIB); Table S4: Cartesian atomic coordinates of model supramolecular cluster.

Author Contributions

Conceptualization, M.K., A.V.S., and D.M.I.; data curation, D.M.I.; formal analysis, A.S.N. and D.M.I.; funding acquisition, A.V.S.; investigation, M.A.K.; methodology, D.M.I.; project administration, D.M.I.; resources, A.V.S.; software, A.S.N.; supervision, M.K. and D.M.I.; validation, M.A.K.; visualization, A.S.N. and D.M.I.; writing—original draft, A.S.N. and D.M.I.; writing—review & editing, M.K. All authors have read and agreed to the published version of the manuscript.

Funding

This work was funded by Russian Science Foundation, grant number 17-73-20185.

Acknowledgments

Physicochemical studies were performed at the Center for X-ray Diffraction Studies belonging to Saint Petersburg State University.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Stahl, P.H.; Wermiuth, C.G.E. Handbook of Pharmaceutical Salts Properties, Selection and Use; Verlag Helvetica Chimica Acta: Zürich, Switzerland, 2002. [Google Scholar]
  2. Trask, A.V. An overview of pharmaceutical cocrystals as intellectual property. Mol. Pharm. 2007, 4, 301–309. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  3. Trask, A.V.; Motherwell, W.D.S.; Jones, W. Pharmaceutical cocrystallization: Engineering a remedy for caffeine hydration. Cryst. Growth Des. 2005, 5, 1013–1021. [Google Scholar] [CrossRef]
  4. Karki, S.; Friščić, T.; Jones, W.; Motherwell, W.D.S. Screening for pharmaceutical cocrystal hydrates via neat and liquid-assisted grinding. Mol. Pharm. 2007, 4, 347–354. [Google Scholar] [CrossRef] [PubMed]
  5. Merkens, C.; Pan, F.F.; Englert, U. 3-(4-Pyridyl)-2,4-pentanedione—A bridge between coordinative, halogen, and hydrogen bonds. CrystEngComm 2013, 15, 8153–8158. [Google Scholar] [CrossRef]
  6. Cinčić, D.; Friščić, T.; Jones, W. Structural Equivalence of Br and I Halogen Bonds: A Route to Isostructural Materials with Controllable Properties. Chem. Mater. 2008, 20, 6623–6626. [Google Scholar] [CrossRef]
  7. Cinčić, D.; Friščić, T.; Jones, W. A cocrystallisation-based strategy to construct isostructural solids. New J. Chem. 2008, 32, 1776–1781. [Google Scholar] [CrossRef]
  8. Bushuyev, O.S.; Tan, D.; Barrett, C.J.; Friščić, T. Fluorinated azobenzenes with highly strained geometries for halogen bond-driven self-assembly in the solid state. CrystEngComm 2015, 17, 73–80. [Google Scholar] [CrossRef]
  9. Cinčić, D.; Friščić, T. Synthesis of an extended halogen-bonded metal-organic structure in a one-pot mechanochemical reaction that combines covalent bonding, coordination chemistry and supramolecular synthesis. CrystEngComm 2014, 16, 10169–10172. [Google Scholar] [CrossRef]
  10. Troff, R.W.; Makela, T.; Topic, F.; Valkonen, A.; Raatikainen, K.; Rissanen, K. Alternative Motifs for Halogen Bonding. Eur. J. Org. Chem. 2013, 2013, 1617–1637. [Google Scholar] [CrossRef]
  11. Cinčić, D.; Friščić, T.; Jones, W. A stepwise mechanism for the mechanochemical synthesis of halogen-bonded cocrystal architectures. J. Am. Chem. Soc. 2008, 130, 7524–7525. [Google Scholar] [CrossRef]
  12. Carletta, A.; Spinelli, F.; d’Agostino, S.; Ventura, B.; Chierotti, M.R.; Gobetto, R.; Wouters, J.; Grepioni, F. Halogen-Bond Effects on the Thermo- and Photochromic Behaviour of Anil-Based Molecular Co-crystals. Chem.: Eur. J. 2017, 23, 5317–5329. [Google Scholar] [CrossRef] [PubMed]
  13. Stilinović, V.; Horvat, G.; Hrenar, T.; Nemec, V.; Cinčić, D. Halogen and Hydrogen Bonding between (N-Halogeno)-succinimides and Pyridine Derivatives in Solution, the Solid State and In Silico. Chem. Eur. J. 2017, 23, 5244–5257. [Google Scholar] [CrossRef] [PubMed]
  14. Kryukova, M.A.; Sapegin, A.V.; Novikov, A.S.; Krasavin, M.; Ivanov, D.M. New Crystal Forms for Biologically Active Compounds. Part 1: Noncovalent Interactions in Adducts of Nevirapine with XB Donors. Crystals 2019, 9, 71. [Google Scholar] [CrossRef] [Green Version]
  15. Kryukova, M.A.; Sapegin, A.V.; Novikov, A.S.; Krasavin, M.; Ivanov, D.M. Non-covalent interactions observed in nevirapinium pentaiodide hydrate which include the rare I4–I− ⋯O=C halogen bonding. Z. Kristallogr. Cryst. Mater. 2019, 234, 101–108. [Google Scholar] [CrossRef]
  16. Wiseman, L.R.; Adkins, J.C. Anastrozole—A review of its use in the management of postmenopausal women with advanced breast cancer. Drugs Aging 1998, 13, 321–332. [Google Scholar] [CrossRef] [PubMed]
  17. Augusto, T.V.; Correia-da-Silva, G.; Rodrigues, C.M.P.; Teixeira, N.; Amaral, C. Acquired resistance to aromatase inhibitors: Where we stand! Endocr.-Relat. Cancer 2018, 25, R283–R301. [Google Scholar] [CrossRef] [Green Version]
  18. Rodgers, R.J.; Reid, G.D.; Koch, J.; Deans, R.; Ledger, W.L.; Friedlander, M.; Gilchrist, R.B.; Walters, K.A.; Abbott, J.A. The safety and efficacy of controlled ovarian hyperstimulation for fertility preservation in women with early breast cancer: A systematic review. Hum. Reprod. 2017, 32, 1033–1045. [Google Scholar] [CrossRef] [Green Version]
  19. Arunan, E.; Desiraju, G.R.; Klein, R.A.; Sadlej, J.; Scheiner, S.; Alkorta, I.; Clary, D.C.; Crabtree, R.H.; Dannenberg, J.J.; Hobza, P.; et al. Definition of the hydrogen bond (IUPAC Recommendations 2011). Pure Appl. Chem. 2011, 83, 1637–1641. [Google Scholar] [CrossRef]
  20. Tang, G.P.; Gu, J.M. 2-[3-(2-cyano-2-propyl)-5-(1,2,4-triazol-1-yl)phenyl]-2-methylpropiononitrile. Acta Cryst. E 2005, 61, O2330–O2331. [Google Scholar] [CrossRef]
  21. Capucci, D.; Balestri, D.; Mazzeo, P.P.; Pelagatti, P.; Rubini, K.; Bacchi, A. Liquid Nicotine Tamed in Solid Forms by Cocrystallization. Cryst. Growth Des. 2017, 17, 4958–4964. [Google Scholar] [CrossRef]
  22. Choquesillo-Lazarte, D.; Nemec, V.; Cinčić, D. Halogen bonded cocrystals of active pharmaceutical ingredients: Pyrazinamide, lidocaine and pentoxifylline in combination with haloperfluorinated compounds. CrystEngComm 2017, 19, 5293–5299. [Google Scholar] [CrossRef]
  23. Sheldrick, G. SHELXT - Integrated space-group and crystal-structure determination. Acta Cryst. A 2015, 71, 3–8. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  24. Dolomanov, O.V.; Bourhis, L.J.; Gildea, R.J.; Howard, J.A.K.; Puschmann, H. OLEX2: A complete structure solution, refinement and analysis program. J. Appl. Cryst. 2009, 42, 339–341. [Google Scholar] [CrossRef]
  25. Agilent Technologies Ltd. CrysAlisPro; Version 1.171.136.120 (release 127-106-2012); Agilent Technologies Ltd.: Santa Clara, CA, USA, 2012. [Google Scholar]
  26. Chai, J.D.; Head-Gordon, M. Long-range corrected hybrid density functionals with damped atom-atom dispersion corrections. Phys. Chem. Chem. Phys. 2008, 10, 6615–6620. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  27. Frisch, M.J.; Trucks, G.W.; Schlegel, H.B.; Scuseria, G.E.; Robb, M.A.; Cheeseman, J.R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G.A.; et al. Gaussian 09, EM64L-G09RevB. 01; Gaussian, Inc.: Wallingford, CT, USA, 2010. [Google Scholar]
  28. Barros, C.L.; de Oliveira, P.J.P.; Jorge, F.E.; Canal Neto, A.; Campos, M. Gaussian basis set of double zeta quality for atoms Rb through Xe: Application in non-relativistic and relativistic calculations of atomic and molecular properties. Mol. Phys. 2010, 108, 1965–1972. [Google Scholar] [CrossRef]
  29. de Berrêdo, R.C.; Jorge, F.E. All-electron double zeta basis sets for platinum: Estimating scalar relativistic effects on platinum(II) anticancer drugs. J. Mol. Struct. THEOCHEM 2010, 961, 107–112. [Google Scholar] [CrossRef]
  30. Jorge, F.E.; Canal Neto, A.; Camiletti, G.G.; Machado, S.F. Contracted Gaussian basis sets for Douglas–Kroll–Hess calculations: Estimating scalar relativistic effects of some atomic and molecular properties. J. Chem. Phys. 2009, 130, 064108. [Google Scholar] [CrossRef]
  31. Neto, A.C.; Jorge, F.E. All-electron double zeta basis sets for the most fifth-row atoms: Application in DFT spectroscopic constant calculations. Chem. Phys. Lett. 2013, 582, 158–162. [Google Scholar] [CrossRef]
  32. Bader, R.F.W. A quantum theory of molecular structure and its applications. Chem. Rev. 1991, 91, 893–928. [Google Scholar] [CrossRef]
  33. Lu, T.; Chen, F. Multiwfn: A multifunctional wavefunction analyzer. J. Comput. Chem. 2012, 33, 580–592. [Google Scholar] [CrossRef]
  34. Oh, S.Y.; Nickels, C.W.; Garcia, F.; Jones, W.; Friščić, T. Switching between halogen- and hydrogen-bonding in stoichiometric variations of a cocrystal of a phosphine oxide. CrystEngComm 2012, 14, 6110–6114. [Google Scholar] [CrossRef]
  35. Desiraju, G.R.; Ho, P.S.; Kloo, L.; Legon, A.C.; Marquardt, R.; Metrangolo, P.; Politzer, P.; Resnati, G.; Rissanen, K. Definition of the halogen bond (IUPAC Recommendations 2013). Pure Appl. Chem. 2013, 85, 1711–1713. [Google Scholar] [CrossRef]
  36. Steiner, T. The hydrogen bond in the solid state. Angew. Chem.-Int. Ed. 2002, 41, 48–76. [Google Scholar] [CrossRef]
  37. Pandiyan, B.V.; Deepa, P.; Kolandaivel, P. How do halogen bonds (S–O⋯I, N–O⋯I and C–O⋯I) and halogen-halogen contacts (C–I⋯I–C, C–F⋯F–C) subsist in crystal structures? A quantum chemical insight. J. Mol. Model. 2017, 23, 16. [Google Scholar] [CrossRef]
  38. Li, L.L.; Liu, Z.F.; Wu, W.X.; Jin, W.J. Cocrystals with tunable luminescence colour self-assembled by a predictable method. Acta Crystallogr. Sect. B 2018, 74, 610–617. [Google Scholar] [CrossRef]
  39. DeHaven, B.A.; Chen, A.L.; Shimizu, E.A.; Salpage, S.R.; Smith, M.D.; Shimizu, L.S. Synergistic effects of hydrogen and halogen bonding in co-crystals of dipyridylureas and diiodotetrafluorobenzenes. Supramol. Chem. 2018, 30, 315–327. [Google Scholar] [CrossRef]
  40. Politzer, P.; Murray, J.S.; Clark, T. Halogen bonding and other s-hole interactions: A perspective. Phys. Chem. Chem. Phys. 2013, 15, 11178–11189. [Google Scholar] [CrossRef]
  41. Murray, J.S.; Politzer, P. Interaction and Polarization Energy Relationships in s-Hole and p-Hole Bonding. Crystals 2020, 10, 76. [Google Scholar] [CrossRef] [Green Version]
  42. Bondi, A. Van der Waals volumes + radii. J. Phys. Chem. 1964, 68, 441–451. [Google Scholar] [CrossRef]
  43. Zhang, K.L.; Hou, C.T.; Song, J.J.; Deng, Y.; Li, L.; Ng, S.W.; Diao, G.W. Temperature and auxiliary ligand-controlled supramolecular assembly in a series of Zn(II)-organic frameworks: Syntheses, structures and properties. CrystEngComm 2012, 14, 590–600. [Google Scholar] [CrossRef]
  44. Zhang, K.L.; Chang, Y.; Ng, S.W. Preparation and characterization of two supramolecular complexes with 5-amino-2,4,6-triiodoisophthalic acid under N-donor auxiliary ligand intervention. Inorg. Chim. Acta 2011, 368, 49–57. [Google Scholar] [CrossRef]
  45. Wang, J.W.; Chen, C.; Li, Y.J.; Luo, Y.H.; Sun, B.W. Halogen-bonding contacts determining the crystal structure and fluorescence properties of organic salts. New J. Chem. 2017, 41, 9444–9452. [Google Scholar] [CrossRef]
  46. Rode, N.D.; Sonawane, A.D.; Garud, D.R.; Joshi, R.R.; Joshi, R.A.; Likhite, A.P. First regioselective iodocyclization reaction of 3-aryl-5-(prop-2-ynylthio)-1H-1,2,4-triazoles. Tetrahedron Lett. 2015, 56, 5140–5144. [Google Scholar] [CrossRef]
  47. Luo, Y.H.; Sun, Y.; Liu, Q.L.; Yang, L.J.; Wen, G.J.; Wang, M.X.; Sun, B.W. Influence of Halogen Atoms on Spin-Crossover Properties of 1,2,4-Triazole-Based 1D Iron(II) Polymers. ChemistrySelect 2016, 1, 3879–3884. [Google Scholar] [CrossRef]
  48. Xiong, H.-P.; Gao, S.-H.; Li, C.-T.; Wu, Z.-J. (2RS)-2-(2,4-Difluorophenyl)-1-[(4-iodobenzyl)(methyl)amino]-3-(1H-1,2,4-triazol-1-yl)propan-2-ol. Acta Cryst. E 2012, 68, o2447–o2448. [Google Scholar] [CrossRef] [Green Version]
  49. Li, L.; Chi, Y.; Mang, X.Y.; Zhang, G.Q.; Zhang, Y.; Zhao, T.X.; Huang, M.; Li, H.B. Synthesis, crystal structure and thermal analysis of tetraiodo-4,4’-bi-1,2,4-triazole. Chin. Chem. Lett. 2013, 24, 786–788. [Google Scholar] [CrossRef]
  50. Il’inykh, E.S.; Kim, D.G.; Kodess, M.I.; Matochkina, E.G.; Slepukhin, P.A. Synthesis of novel fluorine- and iodine-containing [1,2,4]triazolo[3, 4-b][1,3]thiazines based 3-(alkenylthio)-5-(trifluoromethyl)-4H-1,2,4-triazole-3-thiols. J. Fluorine Chem. 2013, 149, 24–29. [Google Scholar] [CrossRef]
  51. Song, J.; Wu, Z.H.; Wangtrakuldee, B.; Choi, S.R.; Zha, Z.H.; Ploessl, K.; Mach, R.H.; Kung, H. 4-(((4-lodophenyl)methyl)-4H-1,2,4-triazol-4-ylamino)-benzonitrile: A Potential Imaging Agent for Aromatase. J. Med. Chem. 2016, 59, 9370–9380. [Google Scholar] [CrossRef]
  52. Nagaradja, E.; Bentabed-Ababsa, G.; Scalabrini, M.; Chevallier, F.; Philippot, S.; Fontanay, S.; Duval, R.E.; Halauko, Y.S.; Ivashkevich, O.A.; Matulis, V.E.; et al. Deprotometalation-iodolysis and computed CH acidity of 1,2,3-and 1,2,4-triazoles. Application to the synthesis of resveratrol analogues. Bioorg. Med. Chem. 2015, 23, 6355–6363. [Google Scholar] [CrossRef] [Green Version]
  53. Dong, Z.; Zhao, T.X.; Li, L.; Zhang, L.J.; Liang, D.H.; Li, H.B. Synthesis and X-Ray Crystal Structures of Tetrahalogeno-4,4’-bi-1,2,4-triazoles. Mol. Cryst. Liq. Cryst. 2015, 623, 333–342. [Google Scholar] [CrossRef]
  54. Al-Salahi, R.; Al-Omar, M.; Marzouk, M.; Ng, S.W. 5-Chloro-2-methylsulfonyl-1,2,4-triazolo[1,5-a]quinazoline. Acta Cryst. E 2012, 68, o1809. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  55. Khan, I.; Panini, P.; Khan, S.U.D.; Rana, U.A.; Andleeb, H.; Chopra, D.; Hameed, S.; Simpson, J. Exploiting the Role of Molecular Electrostatic Potential, Deformation Density, Topology, and Energetics in the Characterization of S⋯N and Cl⋯N Supramolecular Motifs in Crystalline Triazolothiadiazoles. Cryst. Growth Des. 2016, 16, 1371–1386. [Google Scholar] [CrossRef]
  56. Valkonen, J.; Pitkanen, I.; Pajunen, A. Molecular and crystal structure and IR spectrum of 3,5-dibromo-1,2,4-triazole. Acta Chem. Scand. 1985, 39, 711–716. [Google Scholar] [CrossRef]
  57. Berski, S.; Ciunik, Z.; Drabent, K.; Latajka, Z.; Panek, J. Dominant role of C–Br⋯N halogen bond in molecular self-organization. Crystallographic and quantum-chemical study of Schiff-base-containing triazoles. J. Phys. Chem. B 2004, 108, 12327–12332. [Google Scholar] [CrossRef]
  58. Gilandoust, M.; Harsha, K.B.; Madan Kumar, S.; Rakesh, K.S.; Lokanath, N.K.; Byrappa, K.; Rangappa, K.S. 5-Bromo-1,2,4-triazolo[1,5-a]pyrimidine. IUCrData 2016, 1, x161944. [Google Scholar] [CrossRef] [Green Version]
  59. Eccles, K.S.; Morrison, R.E.; Sinha, A.S.; Maguire, A.R.; Lawrence, S.E. Investigating C=S⋯I Halogen Bonding for Cocrystallization with Primary Thioamides. Cryst. Growth Des. 2015, 15, 3442–3451. [Google Scholar] [CrossRef]
  60. Eliseeva, A.A.; Ivanov, D.M.; Novikov, A.S.; Kukushkin, V.Y. Recognition of the π-hole donor ability of iodopentafluorobenzene—A conventional σ-hole donor for crystal engineering involving halogen bonding. CrystEngComm 2019, 21, 616–628. [Google Scholar] [CrossRef]
  61. Mochida, T.; Miura, Y.; Shimizu, F. Assembled Structures and Cation-Anion Interactions in Crystals of Alkylimidazolium and Alkyltriazolium Iodides with Ferrocenyl Substituents. Cryst. Growth Des. 2011, 11, 262–268. [Google Scholar] [CrossRef]
  62. Guino-o, M.A.; Talbot, M.O.; Snits, M.M.; Pham, T.N.; Audi, M.C.; Janzen, D.E. Crystal structures of five 1-alkyl-4-aryl-1,2,4-triazol-1-ium halide salts. Acta Cryst. E 2015, 71, 628–635. [Google Scholar] [CrossRef] [Green Version]
  63. Zhang, W.Y.; Yuan, J.Y. Poly(1-Vinyl-1,2,4-triazolium) Poly(Ionic Liquid)s: Synthesis and the Unique Behavior in Loading Metal Ions. Macromol. Rapid Commun. 2016, 37, 1124–1129. [Google Scholar] [CrossRef] [Green Version]
  64. Gao, Y.; Twamley, B.; Shreeve, J.M. The first (ferrocenylmethyl)imidazollum and (ferrocenylmethyl)triazolium room temperature ionic liquids. Inorg. Chem. 2004, 43, 3406–3412. [Google Scholar] [CrossRef]
  65. Darwich, C.; Karaghiosoff, K.; Klapotke, T.M.; Sabate, C.M. Synthesis and characterization of 3,4,5-Triamino-1,2,4-triazolium and 1-Methyl-3,4,5-triamino-1,2,4-triazolium iodides. Z. Anorg. Allg. Chem. 2008, 634, 61–68. [Google Scholar] [CrossRef]
  66. McCrary, P.D.; Chatel, G.; Alaniz, S.A.; Cojocaru, O.A.; Beasley, P.A.; Flores, L.A.; Kelley, S.P.; Barber, P.S.; Rogers, R.D. Evaluating Ionic Liquids as Hypergolic Fuels: Exploring Reactivity from Molecular Structure. Energy Fuels 2014, 28, 3460–3473. [Google Scholar] [CrossRef] [Green Version]
  67. Elnajjar, F.O.; Binder, J.F.; Kosnik, S.C.; Macdonald, C.L.B. 1,2,4-Triazol-5-ylidenes versus Imidazol-2-ylidenes for the Stabilization of Phosphorus(I) Cations. Z. Anorg. Allg. Chem. 2016, 642, 1251–1258. [Google Scholar] [CrossRef]
  68. Talbot, M.O.; Pham, T.N.; Guino-o, M.A.; Guzei, I.A.; Vinokur, A.I.; Young, V.G. Investigation of ligand steric effect on the hydrogen gas produced via a nickel-catalyzed dehydrogenation of ammonia-borane utilizing unsymmetrical triazolylidene ligands. Polyhedron 2016, 114, 415–421. [Google Scholar] [CrossRef]
  69. Ghazal, B.; Machacek, M.; Shalaby, M.A.; Novakova, V.; Zimcik, P.; Makhseed, S. Phthalocyanines and Tetrapyrazinoporphyrazines with Two Cationic Donuts: High Photodynamic Activity as a Result of Rigid Spatial Arrangement of Peripheral Substituents. J. Med. Chem. 2017, 60, 6060–6076. [Google Scholar] [CrossRef]
  70. Zhang, H.; Wang, Z.Q.; Ghiviriga, I.; Pillai, G.G.; Jabeen, F.; Arami, J.A.; Zhou, W.F.; Steel, P.J.; Hall, C.D.; Katritzky, A.R. Synthesis, characterization and energetic properties of novel 1-methyl-1,2,4-triazolium N-aryl/N-pyridinyl ylids. Tetrahedron Lett. 2017, 58, 1079–1085. [Google Scholar] [CrossRef] [Green Version]
  71. Yan, H.R.; Wang, J.; Yu, Y.H.; Hou, G.F.; Zhang, H.X.; Gao, J.S. Two cationic [(CuxIy)x–y]n motif based coordination polymers and their photocatalytic properties. RSC Adv. 2016, 6, 71206–71213. [Google Scholar] [CrossRef]
  72. Jiang, Y.L.; Wang, Y.L.; Lin, J.X.; Liu, Q.Y.; Lu, Z.H.; Zhang, N.; Jia Jia, W.; Li, L.Q. Syntheses, structures and properties of coordination polymers of cadmium(II) with 4-methyl-1,2,4-triazole-3-thiol ligand. CrystEngComm 2011, 13, 1697–1706. [Google Scholar] [CrossRef]
  73. Li, B.Y.; Peng, Y.; Li, G.H.; Hua, J.; Yu, Y.; Jin, D.; Shi, Z.; Feng, S.H. Design and Construction of Coordination Polymers by 4-Amino-3,5-bis(n-pyridyl)-1,2,4-triazole (n = 2, 3, 4) Isomers in a Copper(I) Halide System: Diverse Structures Tuned by Isomeric and Anion Effects. Cryst. Growth Des. 2010, 10, 2192–2201. [Google Scholar] [CrossRef]
  74. Kuttatheyil, A.V.; Handke, M.; Bergmann, J.; Lassig, D.; Lincke, J.; Haase, J.; Bertmer, M.; Krautscheid, H. 113Cd Solid-State NMR for Probing the Coordination Sphere in Metal-Organic Frameworks. Chem. Eur. J. 2015, 21, 1118–1124. [Google Scholar] [CrossRef]
  75. Wang, X.; Guo, W.; Guo, Y.M. Controllable assemblies of Cd(II) supramolecular coordination complexes based on a versatile tripyridyltriazole ligand and halide/pseduohalide anions. J. Mol. Struct. 2015, 1096, 136–141. [Google Scholar] [CrossRef]
  76. Yan, J.Z.; Lu, L.P. Syntheses, Crystal Structures and Luminescence Properties of Two Cu4I4 Coordination Polymers Based on 3,5-Dialkyl-1,2,4-triazole. Chinese J. Inorg. Chem. 2017, 33, 1697–1704. [Google Scholar] [CrossRef]
  77. Tan, T.T.Y.; Schick, S.; Hahn, F.E. Synthesis and Reactivity of IrIII Complexes Bearing C-Metalated Pyrazolato Ligands. Organometallics 2019, 38, 567–574. [Google Scholar] [CrossRef]
  78. Libnow, S.; Wille, S.; Christiansen, A.; Hein, M.; Reinke, H.; Kockerling, M.; Miethchen, R. Synthesis and reactivity of halogenated 1,2,4-triazole nucleoside analogues with high potential for chemical modifications. Synth.-Stuttg. 2006, 2006, 496–508. [Google Scholar] [CrossRef]
  79. Novikov, A.S.; Ivanov, D.M.; Bikbaeva, Z.M.; Bokach, N.A.; Kukushkin, V.Y. Noncovalent Interactions Involving lodofluorobenzenes: The Interplay of Halogen Bonding and Weak Ip(O)⋯π-Hole(arene) Interactions. Cryst. Growth Des. 2018, 18, 7641–7654. [Google Scholar] [CrossRef]
  80. Bikbaeva, Z.M.; Ivanov, D.M.; Novikov, A.S.; Ananyev, I.V.; Bokach, N.A.; Kukushkin, V.Y. Electrophilic-Nucleophilic Dualism of Nickel(II) toward Ni⋯l Noncovalent Interactions: Semicoordination of Iodine Centers via Electron Belt and Halogen Bonding via σ-Hole. Inorg. Chem. 2017, 56, 13562–13578. [Google Scholar] [CrossRef]
  81. Bikbaeva, Z.M.; Novikov, A.S.; Suslonov, V.V.; Bokach, N.A.; Kukushkin, V.Y. Metal-mediated reactions between dialkylcyanamides and acetamidoxime generate unusual (nitrosoguanidinate)nickel(II) complexes. Dalton Trans. 2017, 46, 10090–10101. [Google Scholar] [CrossRef] [Green Version]
  82. Andrusenko, E.V.; Kabin, E.V.; Novikov, A.S.; Bokach, N.A.; Starova, G.L.; Kukushkin, V.Y. Metal-mediated generation of triazapentadienate-terminated di- and trinuclear μ2-pyrazolate NiII species and control of their nuclearity. New J. Chem. 2017, 41, 316–325. [Google Scholar] [CrossRef] [Green Version]
  83. Mikherdov, A.S.; Novikov, A.S.; Kinzhalov, M.A.; Boyarskiy, V.P.; Starova, G.L.; Ivanov, A.Y.; Kukushkin, V.Y. Halides Held by Bifurcated Chalcogen–Hydrogen Bonds. Effect of μ(S,N–H)Cl Contacts on Dimerization of Cl(carbene)PdII Species. Inorg. Chem. 2018, 57, 3420–3433. [Google Scholar] [CrossRef]
  84. Mikherdov, A.S.; Kinzhalov, M.A.; Novikov, A.S.; Boyarskiy, V.P.; Boyarskaya, I.A.; Avdontceva, M.S.; Kukushkin, V.Y. Ligation-Enhanced π-Hole⋯π Interactions Involving Isocyanides: Effect of π-Hole⋯π Noncovalent Bonding on Conformational Stabilization of Acyclic Diaminocarbene Ligands. Inorg. Chem. 2018, 57, 6722–6733. [Google Scholar] [CrossRef] [PubMed]
  85. Adonin, S.A.; Bondarenko, M.A.; Novikov, A.S.; Abramov, P.A.; Sokolov, M.; Fedin, V.P. Halogen bonding in the structures of pentaiodobenzoic acid and its salts. CrystEngComm 2019, 21, 6666–6670. [Google Scholar] [CrossRef]
  86. Afanasenko, A.M.; Novikov, A.S.; Chulkova, T.G.; Grigoriev, Y.M.; Kolesnikov, I.E.; Selivanov, S.I.; Starova, G.L.; Zolotarev, A.A.; Vereshchagin, A.N.; Elinson, M.N. Intermolecular interactions-photophysical properties relationships in phenanthrene-9,10-dicarbonitrile assemblies. J. Mol. Struct. 2020, 1199, 126789. [Google Scholar] [CrossRef]
  87. Yandanova, E.S.; Ivanov, D.M.; Kuznetsov, M.L.; Starikov, A.G.; Starova, G.L.; Kukushkin, V.Y. Recognition of S⋯CI Chalcogen Bonding in Metal-Bound Alkylthiocyanates. Cryst. Growth Des. 2016, 16, 2979–2987. [Google Scholar] [CrossRef]
  88. Bulatova, M.; Melekhova, A.A.; Novikov, A.S.; Ivanov, D.M.; Bokach, N.A. Redox reactive (RNC)CuII species stabilized in the solid state via halogen bond with I2. Z. Kristallogr. Cryst. Mater. 2018, 233, 371–377. [Google Scholar] [CrossRef]
  89. Rozhkov, A.V.; Novikov, A.S.; Ivanov, D.M.; Bolotin, D.S.; Bokach, N.A.; Kukushkin, V.Y. Structure-Directing Weak Interactions with 1,4-Diiodotetrafluorobenzene Convert One-Dimensional Arrays of [MII(acac)2] Species into Three-Dimensional Networks. Cryst. Growth Des. 2018, 18, 3626–3636. [Google Scholar] [CrossRef]
  90. Kinzhalov, M.A.; Kashina, M.V.; Mikherdov, A.S.; Mozheeva, E.A.; Novikov, A.S.; Smirnov, A.S.; Ivanov, D.M.; Kryukova, M.A.; Ivanov, A.Y.; Smirnov, S.N.; et al. Dramatically Enhanced Solubility of Halide-Containing Organometallic Species in Diiodomethane: The Role of Solvent⋯Complex Halogen Bonding. Angew. Chem. Int. Ed. 2018, 57, 12785–12789. [Google Scholar] [CrossRef]
  91. Zelenkov, L.E.; Ivanov, D.M.; Avdontceva, M.S.; Novikov, A.S.; Bokach, N.A. Tetrachloromethane as halogen bond donor toward metal-bound halides. Z. Kristallogr. Cryst. Mater. 2019, 234, 9–17. [Google Scholar] [CrossRef]
  92. Baykov, S.V.; Dabranskaya, U.; Ivanov, D.M.; Novikov, A.S.; Boyarskiy, V.P. Pt/Pd and I/Br Isostructural Exchange Provides Formation of C–I⋯Pd, C–Br⋯Pt, and C–Br⋯Pd Metal-Involving Halogen Bonding. Cryst. Growth Des. 2018, 18, 5973–5980. [Google Scholar] [CrossRef]
  93. Espinosa, E.; Molins, E.; Lecomte, C. Hydrogen bond strengths revealed by topological analyses of experimentally observed electron densities. Chem. Phys. Lett. 1998, 285, 170–173. [Google Scholar] [CrossRef]
  94. Vener, M.V.; Egorova, A.N.; Churakov, A.V.; Tsirelson, V.G. Intermolecular hydrogen bond energies in crystals evaluated using electron density properties: DFT computations with periodic boundary conditions. J. Comput. Chem. 2012, 33, 2303–2309. [Google Scholar] [CrossRef] [PubMed]
  95. Bartashevich, E.V.; Tsirelson, V.G. Interplay between non-covalent interactions in complexes and crystals with halogen bonds. Russ. Chem. Rev. 2014, 83, 1181–1203. [Google Scholar] [CrossRef]
  96. Espinosa, E.; Alkorta, I.; Elguero, J.; Molins, E. From weak to strong interactions: A comprehensive analysis of the topological and energetic properties of the electron density distribution involving X–H⋯F–Y systems. J. Chem. Phys. 2002, 117, 5529–5542. [Google Scholar] [CrossRef]
Crystals 10 00371 g001 550
Figure 1. Structure of anastrozole with assigned hydrogen bond donor (red) and hydrogen bond acceptor centers (blue) found in its crystal structure (SATHOL) [20].
Figure 1. Structure of anastrozole with assigned hydrogen bond donor (red) and hydrogen bond acceptor centers (blue) found in its crystal structure (SATHOL) [20].
Crystals 10 00371 g001
Crystals 10 00371 g002 550
Figure 2. The C–I⋯N XBs in anastrozole (ASZ)·1.5(1,4-FIB). Hereinafter noncovalent interactions were assigned by dotted lines and ellipsoids are drawn with 50% probability.
Figure 2. The C–I⋯N XBs in anastrozole (ASZ)·1.5(1,4-FIB). Hereinafter noncovalent interactions were assigned by dotted lines and ellipsoids are drawn with 50% probability.
Crystals 10 00371 g002
Crystals 10 00371 g003 550
Figure 3. Bifurcated C–I⋯(I,F) halogen bonding between 1,4-FIB molecules in ASZ·1.5(1,4-FIB).
Figure 3. Bifurcated C–I⋯(I,F) halogen bonding between 1,4-FIB molecules in ASZ·1.5(1,4-FIB).
Crystals 10 00371 g003
Crystals 10 00371 g004 550
Figure 4. The lp(I)⋯π(C) interaction between ASZ and 1,4-FIB molecules in ASZ·1.5(1,4-FIB).
Figure 4. The lp(I)⋯π(C) interaction between ASZ and 1,4-FIB molecules in ASZ·1.5(1,4-FIB).
Crystals 10 00371 g004
Crystals 10 00371 g005 550
Figure 5. The lp(I)⋯π(C) interaction between 1,4-FIB molecules in ASZ·1.5(1,4-FIB).
Figure 5. The lp(I)⋯π(C) interaction between 1,4-FIB molecules in ASZ·1.5(1,4-FIB).
Crystals 10 00371 g005
Crystals 10 00371 g006 550
Figure 6. The C–H⋯N HBs in ASZ·1.5(1,4-FIB).
Figure 6. The C–H⋯N HBs in ASZ·1.5(1,4-FIB).
Crystals 10 00371 g006
Crystals 10 00371 g007 550
Figure 7. Contour line diagrams of the Laplacian distribution ∇2ρ(r), bond paths and selected zero-flux surfaces referring to the C–I⋯X (X = N, F, I) halogen bonding (left) and lp(I)⋯π(triazole) (right) interactions in (ASZ)3·(1,4-FIB)4. Bond critical points (3, −1) are shown in blue, nuclear critical points (3, −3) in pale brown, ring critical points (3, +1) in orange, cage critical points (3, +3) in light green. Length units—Å.
Figure 7. Contour line diagrams of the Laplacian distribution ∇2ρ(r), bond paths and selected zero-flux surfaces referring to the C–I⋯X (X = N, F, I) halogen bonding (left) and lp(I)⋯π(triazole) (right) interactions in (ASZ)3·(1,4-FIB)4. Bond critical points (3, −1) are shown in blue, nuclear critical points (3, −3) in pale brown, ring critical points (3, +1) in orange, cage critical points (3, +3) in light green. Length units—Å.
Crystals 10 00371 g007
Table
Table 1. Parameters of the C–I⋯X XBs in ASZ·1.5(1,4-FIB).
Table 1. Parameters of the C–I⋯X XBs in ASZ·1.5(1,4-FIB).
C–I⋯Xd(I⋯X), ÅRIX b∠(C–I⋯X),°
C8S–I3S⋯N22.913 (6)0.83175.3 (2)
C1S–I1S⋯N32.883 (7)0.82169.3 (2)
C4S–I2S⋯F6S 3.390 (5)0.98149.97 (19)
C4S–I2S⋯I3S3.8529 (8)0.97157.68 (18)
Comparison a3.53 (I⋯N)
3.45 (I⋯F)
3.96 (I⋯I)		1.00180
a Comparison is the vdW radii sum [42] for distances and classic XB angle. b RIX = d(I⋯X)/(RvdW(I) + RvdW(X)).
Table
Table 2. Parameters of the lp(I)⋯π(C) interactions in ASZ·1.5(1,4-FIB).
Table 2. Parameters of the lp(I)⋯π(C) interactions in ASZ·1.5(1,4-FIB).
C⋯I–Cd(C⋯I), ÅRCI b∠(C⋯I–C),°
C9⋯I1S–C1S3.528 (8)0.9686.6(3)
C9S⋯I2S–C4S3.686 (8)1.0092.9(3)
Comparison a3.681.0090
a Comparison is the vdW radii sum [42] for distances and classic XB acceptor angle. b RCI = d(C⋯I)/(RvdW(I) + RvdW(C)).
Table
Table 3. Parameters of the C–H⋯N HBs in ASZ·1.5(1,4-FIB).
Table 3. Parameters of the C–H⋯N HBs in ASZ·1.5(1,4-FIB).
C–H⋯Nd(H⋯N), ÅRHN bd(C⋯N), Å∠(C–I⋯X),°
C7–H7A⋯N5 2.4840.903.441 (10)168.6
C16–H16B⋯N4 2.7330.993.62 (1)153.9
Comparison a2.751.003.25110.0
a Comparison is the vdW radii sum [42] for distances and minimal HB angle. b RHN = d(H⋯N)/(RvdW(H) + RvdW(N)).
Table
Table 4. Values of the density of all electrons—ρ(r), Laplacian of electron density—∇2ρ(r), energy density—Hb, potential energy density—V(r), and Lagrangian kinetic energy—G(r) (a.u.) at the bond critical points (3, −1), corresponding to different non-covalent interactions in (ASZ)3·(1,4-FIB)4, bond lengths—l (Å), as well as energies for these contacts Eint (kcal/mol), defined by two approaches.*.
Table 4. Values of the density of all electrons—ρ(r), Laplacian of electron density—∇2ρ(r), energy density—Hb, potential energy density—V(r), and Lagrangian kinetic energy—G(r) (a.u.) at the bond critical points (3, −1), corresponding to different non-covalent interactions in (ASZ)3·(1,4-FIB)4, bond lengths—l (Å), as well as energies for these contacts Eint (kcal/mol), defined by two approaches.*.
Contactρ(r)∇2ρ(r)HbV(r)G(r)EintaEintbl
I3S⋯N20.0220.0700.000−0.0170.0175.34.62.913
I1S⋯N30.0240.0720.000−0.0190.0186.04.82.883
I2S⋯F6S0.0060.0260.001−0.0040.0051.31.33.390
I2S⋯I3S0.0080.0310.001−0.0050.0061.61.63.853
C9⋯I1S0.0090.0290.001−0.0050.0061.61.63.528
C9S⋯I2S0.0060.0230.001−0.0030.0040.91.13.686
H7A⋯N50.0090.0330.001−0.0060.0071.91.92.484
H16B⋯N40.0050.0210.001−0.0030.0040.91.12.733
a Eint = −V(r)/2 [93] b Eint = 0.429G(r) [94] * Note that Tsirelson et al. [95] also proposed alternative correlations developed exclusively for non-covalent interactions involving iodine atoms, viz. Eint = 0.68(−V(r)) or Eint = 0.67G(r).

Share and Cite

MDPI and ACS Style

Kryukova, M.A.; Sapegin, A.V.; Novikov, A.S.; Krasavin, M.; Ivanov, D.M. New Crystal Forms for Biologically Active Compounds. Part 2: Anastrozole as N-Substituted 1,2,4-Triazole in Halogen Bonding and Lp-π Interactions with 1,4-Diiodotetrafluorobenzene. Crystals 2020, 10, 371. https://doi.org/10.3390/cryst10050371

AMA Style

Kryukova MA, Sapegin AV, Novikov AS, Krasavin M, Ivanov DM. New Crystal Forms for Biologically Active Compounds. Part 2: Anastrozole as N-Substituted 1,2,4-Triazole in Halogen Bonding and Lp-π Interactions with 1,4-Diiodotetrafluorobenzene. Crystals. 2020; 10(5):371. https://doi.org/10.3390/cryst10050371

Chicago/Turabian Style

Kryukova, Mariya A., Alexander V. Sapegin, Alexander S. Novikov, Mikhail Krasavin, and Daniil M. Ivanov. 2020. "New Crystal Forms for Biologically Active Compounds. Part 2: Anastrozole as N-Substituted 1,2,4-Triazole in Halogen Bonding and Lp-π Interactions with 1,4-Diiodotetrafluorobenzene" Crystals 10, no. 5: 371. https://doi.org/10.3390/cryst10050371

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop