Preference in the Type of Halogen Bonding Interactions within Co-Crystals of Anthraquinone with a Pair of Isosteric Perhalobenzenes

Abstract

The preference in the type of halogen bond accepted by anthraquinone (C₁₄H₈O₂) from two isosteric donors, namely 1,4-diiodoperfluorobenzene (C₆I₂F₄) and 1,4-diiodoperchlorobenzene (C₆I₂Cl₄), is reported. The two co-crystals, (C₆I₂F₄)·(C₁₄H₈O₂) and (C₆I₂Cl₄)·(C₁₄H₈O₂), are sustained primarily by I···O rather than π-type halogen bonds to form these multicomponent solids. The ability for each component to engage in two divergent halogen-bonding interactions generates a one-dimensional chain structure for each co-crystal. The bias in the halogen-bonding type is due to the difference in electrostatic potential between the carbonyl oxygen and the aromatic surface on the anthraquinone. To support this observed preference, the binding energies of the I···O halogen bond were quantified for both co-crystals by using density functional theory calculations and then compared to the interaction energy for related π-type halogen bond from previously reported structures.

1. Introduction

Halogen bonding is an attractive non-covalent interaction between an electrophilic region on a halogen atom and a nucleophilic region on a different atom [1,2]. This electrophilic or positive region is defined as the σ-hole, which is found along the bond axis between a halogen and carbon atom. In general, the σ-hole is enhanced, with a larger positive value, when iodine is in the presence of neighboring electronegative atoms [3,4]. As a result of electrostatic attraction, the σ-hole interacts with an electron-rich atom or group to form a halogen bond. Normally, these halogen bonds are classified as n-type, where the σ-hole is interacting with a lone pair on a heteroatom such as nitrogen or oxygen. In contrast, π-type halogen bonds are observed between an electrophilic halogen atom and a polycyclic aromatic surface and are considerably less common [5,6].

The most investigated and reported aromatic halogen-bond donor continues to be 1,4-diiodoperfluorobenzene (C₆I₂F₄). This is due to the greater electron-withdrawing ability of fluorine when compared to other halogen atoms. As a result, the fluorine atoms within C₆I₂F₄ generate the largest positive σ-hole on the iodine atoms, making this an ideal aromatic donor. Due to this fact, C₆I₂F₄ has been shown to engage in both n-type [7,8,9] and π-type [10,11] halogen bonds to form numerous co-crystals or multi-component molecular solids.

A continued focus of our research groups has been the design and formation of co-crystals that utilize 1,4-diiodoperchlorobenzene (C₆I₂Cl₄) as a halogen-bond donor [12,13,14]. In particular, we have investigated the ability of C₆I₂Cl₄ to behave as a template to align various pyridine-based reactants in a suitable position to undergo the solid-state [2 + 2] cycloaddition reaction [15,16,17]. In these co-crystals, the constituent molecules are held together by I···N (i.e., n-type) halogen bonds to form photoreactive solids. Unlike co-crystals containing C₆I₂F₄, an advantage of using C₆I₂Cl₄ as a template is its tendency to engage in homogeneous and face-to-face π-π stacking interactions [18] that, along with the I···N halogen bond, position a pair of reactant molecules within the correct distance and orientation for a photoreaction [19]. Recently, we also investigated the ability of C₆I₂Cl₄ to form a π-type halogen bond to a polyaromatic molecule, namely naphthalene [20]. The initial selection of naphthalene was based upon its polyaromatic structure, along with a lack of a heteroatom, precluding competition for the π-type halogen bond within the co-crystal. To expand this research further and to understand the tendencies of C₆I₂F₄ and C₆I₂Cl₄ as donors, we investigated what type of halogen bond would be preferred when co-crystallized with a polycyclic aromatic that contains heteroatoms.

Using this as inspiration, we report here the structure of a pair of co-crystals based upon anthraquinone (C₁₄H₈O₂) with either C₆I₂F₄ or C₆I₂Cl₄, where the I···O halogen bond is preferred over π-type interactions in these molecular solids (Scheme 1). These co-crystals have similar formulas, namely (C₆I₂F₄)·(C₁₄H₈O₂) and (C₆I₂Cl₄)·(C₁₄H₈O₂), where, in both cases, the I···O halogen bonds generate a one-dimensional chain structure. Curiously, the co-crystals are not isostructural even though they contain a molecule in common and the halogen-bond donors are isosteric (i.e., similar shape) in nature. In particular, neighboring chains in (C₆I₂F₄)·(C₁₄H₈O₂), the donor engages in both C-H···F and C=O···π interactions with the acceptor. In addition, molecules of C₁₄H₈O₂ are found to π-π stack in an offset and face-to-face pattern in the co-crystal. In contrast, the chains within (C₆I₂Cl₄)·(C₁₄H₈O₂) for both the donor and acceptor molecules interact with its nearest neighbors by homogeneous and face-to-face π-π stacking forces, as seen with other co-crystals containing C₆I₂Cl₄. Lastly, these polymeric chains interact via Type I chlorine–chlorine interactions to form an extended structure.

The preference of the I···O halogen bond over the π-type interaction in these co-crystals is based upon the larger negative electrostatic potential on the oxygen atom when compared to the aromatic surface of the acceptor. While electrostatic potentials are a useful tool in the understanding and design of halogen-bonded systems, the role of charge transfer in halogen bonding has garnered greater recognition in the area of crystal engineering [21,22]. Finally, the selectivity in the type of halogen bond was investigated by performing a series of density functional theory (DFT) calculations to determine the binding energy of the I···O halogen bond in both co-crystals. These values were then compared to the binding energies for π-type halogen bonds for related co-crystals, illustrating that I···O halogen bonds form stronger non-covalent interactions and, in turn, are observed within these molecular solids.

2. Materials and Methods

2.1. Materials

The donor, 1,4-diiodoperfluorobenzene (C₆I₂F₄), and the acceptor, anthraquinone (C₁₄H₈O₂), were both purchased from Sigma-Aldrich Chemical (St. Louis, MO, USA) and were used without purification. The two solvents, namely toluene and chloroform, were also purchased from Sigma-Aldrich Chemical and were used as received. The donor, 1,4-diiodoperchlorobenzene (C₆I₂Cl₄), was synthesized by a previously reported method [23]. All of the crystallization studies were performed in 20 mL scintillation vials.

2.2. Formation of (C₆I₂F₄)·(C₁₄H₈O₂)

The formation of the co-crystal (C₆I₂F₄)·(C₁₄H₈O₂) was achieved by dissolving 25.0 mg of C₆I₂F₄ in 2.0 mL of chloroform, which was then added to a separate solution of 12.9 mg of C₁₄H₈O₂ in 2.0 mL of chloroform (1:1 molar equivalent). The combined solution was then allowed to evaporate slowly. Within two days, after some loss of solvent, single crystals suitable for X-ray diffraction were formed.

2.3. Formation of (C₆I₂Cl₄)·(C₁₄H₈O₂)

The formation of the co-crystal (C₆I₂Cl₄)·(C₁₄H₈O₂) was achieved by dissolving 25.0 mg of C₆I₂Cl₄ in 2.0 mL of toluene, which was then combined with 11.2 mg of C₁₄H₈O₂ in a separate 2.0 mL toluene solution (1:1 molar equivalent). The resulting solution was then allowed to slowly evaporate. Within a day, and along with loss of solvent, single crystals suitable for X-ray diffraction were realized.

2.4. Electrostatic Potential Calculations

The molecular electrostatic potential energy surface for C₁₄H₈O₂ was calculated by using Spartan’20 molecular modeling program, using density functional theory (DFT) at the B3LYP/6- 311++G** level [24]. Previously, we reported the calculated values of the σ-hole on iodine within both C₆I₂F₄ and C₆I₂Cl₄ to be 168.9 and 145.7 kJ/mol, respectively [15]. Both of these values are well within range for a halogen-bond donor. With respect to C₁₄H₈O₂, the electrostatic potential energies were determined and returned a minimum value of −154.3 kJ/mol on the carbonyl oxygen, atom along with a minimum of −40 kJ/mol for the aromatic ring (Scheme 2).

With regard to the perhalobenzenes, namely C₆I₂F₄ and C₆I₂Cl₄, the aromatic rings are electron poor in nature and may potentially accept C=O···π interactions [25,26,27]. To this end, the maximum electrostatic potential on the surface of the benzene ring within C₆I₂F₄ has a value of 81 kJ/mol at a point between two fluorine-bearing carbon atoms. In contrast, the largest electrostatic potential on C₆I₂Cl₄ is only 54 kJ/mol and is located in the center of the benzene ring.

2.5. Computational Methods

To determine the binding energies for the I···O and π-type halogen bonds, a series of density functional theory (DFT) calculations were performed using the M06-2X density functional in the Gaussian 16 program [28]. The aug-cc-pVTZ basis set, stored in the Gaussian program, was used on all atoms except iodine. In the case of iodine, the basis set included a core potential that replaces the inner 28 electrons and was obtained from the EMSL Basis Set Exchange Library [29]. This DFT approach determines the binding energy as the difference between the acceptor and donor in the co-crystal and the two separated molecules. These binding energies were all computed using the counterpoise method, which normally decreases the value by around five-to-ten percent. The overall I···O and π-type halogen-bond energies for a given co-crystal were calculated by using atomic positions determined from the single-crystal X-ray diffraction data.

2.6. Single-Crystal X-ray Diffraction

X-ray data were collected on a Bruker D8 VENTURE DUO diffractometer (Bruker, Germany), using Mo Kα radiation (λ = 0.71073 Å) and a PHOTON III detector. Crystals were transferred from the vial and placed on a glass slide in Paratone-N oil. A crystal, along with a small amount of oil, was collected on a MiTeGen 100-micron MicroLoop. Then, the selected crystal was transferred to the instrument, where it was placed under a cold nitrogen stream at 100 K. After data collection, the unit cell was determined using a subset of all the collected data. All intensity data were corrected for Lorentz, polarization, and background effects, using the program APEX5 (version 2023.9-2). A semi-empirical correction was applied for the adsorption, using SADABS. The program SHELXT [30] was used for the initial structure solution, while SHELXL [31] was used for the refinement of the structure. Both programs were utilized within the OLEX2 software [32]. Selected crystallographic and refinement parameters for both (C₆I₂F₄)·(C₁₄H₈O₂) and (C₆I₂Cl₄)·(C₁₄H₈O₂) are listed in

Table 1. Crystallographic and refinement parameters for the halogen-bonded co-crystals (C₆I₂F₄)·(C₁₄H₁₀O₂) and (C₆I₂Cl₄)·(C₁₄H₁₀O₂).

Co-crystal	(C6I2F4)·(C14H8O2)	(C6I2Cl4)·(C14H8O2)
Formula	C20H8F4I2O2	C20H8Cl4I2O2
Formula mass (g·mol−1)	610.06	675.86
Crystal system	monoclinic	triclinic
Space group	P21/c	Pī
a (Å)	11.3817(5)	4.0473(4)
b (Å)	5.9765(3)	8.0764(10)
c (Å)	13.5850(6)	15.2448(18)
α (°)	90	84.625(4)
β (°)	101.652(1)	86.055(4)
γ (°)	90	86.488(4)
Z	2	1
V (Å3)	905.05(7)	494.20(10)
ρcalcd (g·cm−3)	2.239	2.271
T (K)	100	100
μ (mm−1)	3.528	3.738
F(000)	572.0	318.0
Radiation source	Mo Kα	Mo Kα
Reflections collected	22,414	29,776
Independent reflections	2240	2455
Data/restraints/parameters	2240/0/127	2455/0/128
Rint	0.0334	0.0575
R1 (I ≥ 2σ(I))	0.0154	0.0190
wR (F2) (I ≥ 2σ(I))	0.0374	0.0399
R1 (all data)	0.0170	0.0208
wR (F2) (all data)	0.0381	0.0407
Goodness-of-net on F2	1.137	1.107
CCDC deposition number	2,339,495	2,332,122

.

3. Results

3.1. X-ray Crystal Structure of (C₆I₂F₄)·(C₁₄H₈O₂)

Single-crystal X-ray diffraction data determined that (C₆I₂F₄)·(C₁₄H₈O₂) crystalizes in the centrosymmetric monoclinic space group P2₁/c. Within the asymmetric unit is one half of both C₆I₂F₄ and C₁₄H₈O₂ where inversion symmetry generates the remainder of each molecule. The co-crystal is held together by I···O halogen bonds (I···O 2.983(1) Å; C-I···O 169.02(5)°) to generate a one-dimensional chain structure (Figure 1). The donor and acceptor aromatic rings are rotated from co-planar by 72.64° within the chain (Figure 1). In addition to the halogen bond, the molecular components are also engaged in C=O···π interactions, with the closest contact being between an oxygen atom and a pair of fluorinated carbon atoms (O···C 3.080(2) and 3.086(2) Å; C=O···C 112.77(12) and 126.42(12)°) [25,26,27] (Figure 1). The location of this non-covalent interaction correlates with the position of the maximum electrostatic potential on the surface of C₆I₂F₄. In addition, molecules of C₁₄H₈O₂ are involved in an offset and face-to-face π-π stacking arrangement that generates a homogeneous column at a planar distance of 3.467 Å (Figure 2). Lastly, these halogen-bonded chains interact with their nearest neighbors by C-H···F contacts [33] (C···F 3.275(2) and 3.512(2) Å; C-H···F 141.39(12) and 155.12(12)°) (Figure 3). The combination of these non-covalent interactions results in a three-dimensional extended co-crystal.

3.2. X-ray Crystal Structure of (C₆I₂Cl₄)·(C₁₄H₈O₂)

Single-crystal diffraction data determined that the molecular components of (C₆I₂Cl₄)·(C₁₄H₈O₂) crystalize in the centrosymmetric triclinic space group Pī. The asymmetric unit contains a half of a molecule of both C₆I₂Cl₄ and C₁₄H₈O₂, where inversion symmetry generates each whole molecule. The co-crystal is primarily sustained by I···O halogen bonds (I···O 2.930(2) Å; C-I···O 174.59(7)°), which generate a one-dimensional chain structure (Figure 4). Within the halogen-bonded polymer, the aromatic rings are rotated from co-planarity by 57.65° (Figure 4). As seen in single- and multi-component solids containing C₆I₂Cl₄, the ditopic halogen-bond donor is found to engage in an infinite homogeneous and face-to-face π-π stacking arrangement (Figure 4). Due to this type of stacking pattern, along with the I···O halogen bonds, both the donor and acceptor are found parallel and slightly offset π-stacking with a centroid-to-centroid distance of 4.0473(4) Å, which is equal to the crystallographic a-axis. Lastly, these chains also interact with their nearest neighbors by Type I chlorine–chlorine interactions [34,35] (Cl···Cl 3.4878(9) Å; C-Cl···Cl 146.87(8), and 145.93(8)°; |θ₁ − θ₂| = 0.94°) (Figure 5). The combination of these non-covalent interactions generates a three-dimensional extended solid.

3.3. Halogen Bond Energies Using Density Functional Theory Calculations

To enumerate the strength of the I···O halogen bond within both (C₆I₂F₄)·(C₁₄H₈O₂) and (C₆I₂Cl₄)·(C₁₄H₈O₂), a theoretical investigation using density functional theory (DFT) was performed using the M062X density functional at the aug-cc-pVTZ basis set. The I···O halogen bond binding energies were determined to be −18.2 and −17.9 kJ/mol for (C₆I₂F₄)·(C₁₄H₈O₂) and (C₆I₂Cl₄)·(C₁₄H₈O₂), respectively. In comparison, the binding energy for a π-type halogen bond for both donors was also calculated in order to compare the energetic differences. In particular, a co-crystal containing C₆I₂F₄ and anthracene [11] was selected, along with a solid based upon C₆I₂Cl₄ and naphthalene [20]. Again, the DFT calculations used atomic positions from the published diffraction data. The binding energies for π-type halogen bonds between C₆I₂F₄ and anthracene returned values of −16.0 and −15.9 kJ/mol. Similarly, the co-crystal containing C₆I₂Cl₄ and naphthalene had a binding energy of −13.6 kJ/mol for the π-type halogen bond. In both examples, the I···O halogen bond returned a higher value for the binding energy than the π-type halogen bond, which supports the observed bias in these reported co-crystals.

4. Conclusions

In this contribution, we report the preference of I···O over π-type halogen bonds in a pair of co-crystals, namely (C₆I₂F₄)·(C₁₄H₈O₂) and (C₆I₂Cl₄)·(C₁₄H₈O₂). This selectivity in the type of halogen bond is largely based upon the difference in electrostatic potential energy between the carbonyl oxygen and the aromatic surface of the acceptor. Each component is ditopic, either donating or accepting two I···O halogen bonds, thereby generating a one-dimensional chain structure in both co-crystals. We note that the observation of C=O···π interactions in the co-crystal (C₆I₂F₄)·(C₁₄H₈O₂) is consistent with the enhanced electrophilic nature of C₆I₂F₄ relative to the chlorinated analogue C₆I₂Cl₄. Currently, we are investigating the formation of related co-crystals with other polycyclic aromatics that contain different heteroatoms.