*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 [37–39], which confirm the σ-hole electrophilicity [40,41] of iodine atoms in this molecule.


**Table 1.** Parameters of the C–I· · · X XBs in **ASZ**·1.5(**1,4-FIB**).

<sup>a</sup> Comparison is the vdW radii sum [42] for distances and classic XB angle. <sup>b</sup> RIX = *d*(I· · · X)/(RvdW(I) + RvdW(X)).

**1,4-FIB** [34].

*2.4. Computational Details* 

**3. Results and Discussion** 

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

39], which confirm the σ-hole electrophilicity [40,41] of iodine atoms in this molecule.

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 [28–31] 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

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

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

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":

supramolecular cluster are presented in Supporting Information, Table S4.

details on the powder x-ray diffraction experiments see also Section 2.3.

**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. *Comparison a 3.45 (I···F) 3.96 (I···I) 1.00 180*  a Comparison is the vdW radii sum [42] for distances and classic XB angle. b RIX = *d*(I···X)/(RvdW(I) + RvdW(X)).

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 4*H*-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 [44,46–52]. 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 [53–55] and C–Br· · · N [45,53,56–58] XBs including 1,2,4-triazole moiety are also mentioned in the literature. 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 4*H*-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 [44,46–52]. 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 [53–55] and C–Br···N [45,53,56–58] 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. 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.

**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**).

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. 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
