2021, Vol.94, No.1

A distinct difference between the three-center halogen bond and the analogous three-center coordinative bond of silver is demonstrated by computational, X-ray crystallographic and solution NMR spectroscopic investigations of their complexes with a bidentate Lewis base. Iodine(I) preferentially forms an entropically favored monomeric complex, whereas silver(I) forms enthalpically favored dimeric complexes. Counterion coordination considerably influences the structure of the silver complexes in the solution and solid state, whereas it does not have notable effect on the analogous halogen bond.

Halogen bonding is the directional interaction between an electron-poor area of a halogen and a Lewis base.1 Due to its growing range of applications including molecular recognition, self-assembly, medicinal chemistry, organic synthesis and catalysis,28 halogen bonding is rapidly gaining attention. Being a weak force, halogen bonding is challenging to detect in solution.9 Accordingly, studying halogen bonds in solution typically requires strong halogen bond donors, whose electrophilicity is amplified by either appending electron withdrawing groups,10 or by oxidation of the halogen bond donor to an electron deficient halonium ion, X+.11 A common feature of both strategies is that they aim to increase the electron deficiency of the halogen, which makes it a stronger halogen bond donor. Obviously, a positively charged halogen, X(I)11,12 or X(III),13,14 has the capacity to be a very strong halogen bond donor. Halonium ions, X+, typically form linear three-center, four-electron halogen bonds, [D⋯X⋯D]+, in which the halogen (X) simultaneously interacts with two Lewis bases (D). These both donate a lone pair of electrons each into the empty p-orbital of the halonium ion, giving rise to a strong charge-transfer interaction.

Three-center halogen bonds have so far been formed with ligands that are preorganized to offer optimal distances and angles for intramolecular or intermolecular stabilization of halonium ions,1520 or are fully flexible.21 Halogen bonds of conformationally restricted Lewis bases (D) that enthalpically disfavor the formation of intramolecular bonds have not yet been assessed. Herein, we evaluate the iodine(I) complex of such a ligand, 1, (Figure 1, top) and compare it to the silver(I) coordination complex of 1 using solution NMR spectroscopic, single crystal X-ray diffraction and computational (DFT) techniques. In addition, we investigate the influence of the counterion on the complexes.

2.1 Design.

Previous studies have shown that the global energy minimum of a fully flexible [bis(pyridine)iodine(I)]+ halogen bond complex is centrosymmetric with a nitrogen-nitrogen distance (rNN) of 4.51 Å.22 The symmetric halogen bond geometry is also preferred in slightly strained systems, such as 2 (Figure 1, middle), allowing rNN ≤ 4.88 Å, whereas above this distance the asymmetric [N–I⋯N]+ arrangement becomes energetically most favorable. The preference of halonium ions for forming symmetric over asymmetric halogen bonds has been demonstrated in a geometrically restricted bis(pyridine) ligand 3, (Figure 1, bottom) that enforces a long, rNN = 6.1 Å, nitrogen-nitrogen distance.22 This ligand prefers to form a dimer with two symmetric three-center halogen bonds over the monomeric complex with asymmetric halogen bonds. The former is an entropically disfavored dimer that has enthalpically favored strong and symmetric halogen bonds. In contrast, the latter, is an entropically favored monomer that has enthalpically disfavored weaker, asymmetric halogen bonds. The halogen bonds of conformationally flexible ligands that may allow symmetric three-center halogen bond (rNN ≤ 4.88 Å) complexes to form only at the cost of significant strain have not yet been investigated. Such complexes balance entropic and enthalpic factors, and may accordingly either form monomeric species with a strained three-center halogen bond or higher-order aggregates possessing strong, symmetric three-center halogen bonds. The geometry of the halogen bond complex of such a ligand is expected to be inherently challenging to predict due to the delicate (im)balance of entropic and enthalpic contributions determining its preferred geometry. Herein, we investigate ligand 1 which has rNN ∼ 4.7 Å in its monomeric [N⋯I⋯N]+ complex, allowing formation of a slightly destabilized yet symmetric halogen bond. As the core of 1 is more adaptable than the previously studied bidentate bis(pyridine)-type donors,15,22 it may allow for the formation of not just monomeric, but also dimeric or polymeric halogen bond assemblies. Thus, energetically favorable short and symmetric three-center [N⋯I⋯N]+ bonds might compensate for the unfavorable entropic consequence of the dimer or oligomer formation.

The properties of three-center, four-electron halogen bonds are typically compared to analogous [D⋯H⋯D]+ hydrogen and [D⋯Ag⋯D]+ metal coordination bonds.11,12,23 The former prefers an asymmetric geometry, with a distinct covalent and a distinct secondary bond, while the latter is centrosymmetric. Three-center halogen bonds have occasionally been referred to as coordinative bonds.24 However, halogen bonds of halonium ions differ from metal coordinative bonds concerning their solvation and counterion coordination,25,26 which leads to important structural differences, for example in supramolecular assemblies.17 Based on this knowledge, comparison of the silver(I) and iodine(I) complexes of 1 is expected to provide deeper understanding of three-center complexes.

Bis(pyridine) complexes of iodine(I), bromine(I) and chlorine(I) have been demonstrated to exist in comparable geometries and have analogous properties, despite the altering extent of electrostatic and charge-transfer components of their halogen bonds.27 Accordingly, most fundamental studies and supramolecular applications so far have focused on the investigation of iodine(I) complexes in order to draw general conclusions about the halogen bonds of halonium ions.11,1520,22,2427 Moreover, the three-center [N⋯Ag⋯N]+ bond of silver(I) in the bis(pyridine) complex has been shown to be similar to the analogous Au(I) complex in solution, the solid state and in silico.23 The analysis of statistical trends from X-ray crystallographic observations, using data obtained from the Cambridge Structural Database (CSD) indicated that the bis(pyridine) complexes of other transition metals, such as Hg(II), Cd(II), Te(III), Er(III), Zn(II), Gd(III), Mn(II), Fe(II), Ni(II), Cr(II), and Rh(I) also form linear and symmetric bis(pyridine)metal(I-III) three-center complexes with comparable geometries.23 Accordingly, the analyses of iodine(I) and silver(I) complexes are expected to provide general conclusions to compare the bonding of halonium and transition metal complexes. Previous work suggests11,12,2527 that the main origin of the difference between the behavior of the halogen and transition metal complexes is the availability of empty d-orbitals in the latter. This allows coordination of Lewis bases to the metal center. In contrast, the s2(d10)p4 electron configuration of halogens makes them inert for coordination of Lewis bases, such as counter anions and solvents.

2.2 Computational Analysis.

We have computationally investigated the potential [N⋯X⋯N]+ complexes of ligand 1 (see ESI for details). Our main goal was to analyze the structure and relative stability of the monomeric and dimeric forms of these complexes in solution phase. The counter anions were not included in our calculations, as we only model complexes with weakly coordinating anions. Computations predict that dimeric structures for both silver(I) and iodine(I) complexes of 1 are favored thermodynamically as compared to the monomeric structures (Figure 2). The closed (cl) forms of monomeric complexes possessing symmetric three-center, four-electron [N⋯X⋯N]+ bonds (1-Ag-cl and 1-I-cl) are strained, as indicated by their distorted binaphthyl framework and the increased rXN bond distances. The open (op) structure of monomeric iodine(I) complex (1-I-op) is predicted to be slightly more favored over 1-I-cl, supporting the strained nature of 1-I-cl. For silver(I), the open monomeric form (1-Ag-op) involves Ag+-arene coordination, however, this structure is computed to be less stable than 1-Ag-cl. Two types of dimeric species were identified computationally for both 1-Ag and 1-I. The A-type structures are characterized by large separation of X+ ions, whereas the cations are much closer in the B-type forms. The [N⋯X⋯N]+ unit is symmetrical in these dimeric forms and their structures are analogous to those identified computationally for iodine(I) complexes of a phenanthrene-based ligand.22

2.3 Synthesis.

3,3′-di(pyridin-2-yl)-1,1′-binaphthalene 1 was prepared following the synthetic route shown in Scheme 1 (see ESI for details). Compound 4 was synthesized by addition of bromine to a CCl4 solution of naphthalene while irradiating the reaction mixture with a 1000 W Xe ARC lamp. Compound 4 was dehydrobrominated using potassium tert-butoxide. Compound 5 was then converted to 6 via Stille coupling with 2-(tributylstannyl)pyridine. Compound 7 was synthesized from 6 by a palladium(II)-catalysed reaction with bis(pinacolato)diboron. Suzuki coupling between 6 and 7 yielded ligand 1. Ligand 1 was converted into silver(I) coordination complexes by addition of Ag(I) salts to CH2Cl2 solutions of 1, yielding 1-Ag-BF4, 1-Ag-PF6, 1-Ag-OTf, 1-Ag-CO2CF3, and 1-Ag-OTs. Formation of an [N⋯Ag⋯N]+ coordination complex was confirmed by the Δδ15Ncoord coordination shift of 44 ppm (1-Ag-OTf). Halogen bond complexes were prepared following a reported procedure,15 by addition of I2 into a CD3CN or CD2Cl2 solution of the Ag(I) complex of ligand 1, yielding the complexes 1-I-BF4, 1-I-PF6, 1-I-OTf, 1-I-CO2CF3, and 1-I-OTs. The formation of [N⋯I⋯N]+ complexes was confirmed by the Δδ15Ncoord of 100–105 ppm, which is comparable to the coordination shifts reported for analogous complexes.15,16,22,26

2.4 Solid State Structures from X-ray Crystallography.

To further elucidate the composition of the 1-Ag complexes with different anions, single crystals suitable for X-ray diffraction studies were obtained via slow diffusion of hexane into CH2Cl2 solutions of 1 with Ag-PF6 (CCDC 2025121), Ag-CO2CF3 (CCDC 2025119), and Ag-OTs (CCDC 2025120). The three different complexes formed in the solid state highlight distinct anion coordination to the silver(I) atoms which, when paired with the conformational flexibility of 1, produce different dimeric complexes and a coordination polymer.

1-Ag-CO2CF3 crystallizes in the P21/n space group with two silver(I) complexes in the asymmetric unit. Each complex consists of a collapsed dimer that incorporates two silver(I) ions and two molecules of 1 (Figure 3a). The dimer resembles the A-type dimers described in the theoretical discussion. Interestingly, the collapsed dimer allows facial π-stacking between the naphthalene ring of one ligand and the pyridine ring of the other ligand. One main difference between the X-ray and computed structures is the presence of anions. In the X-ray structure, each silver(I) ion has a pseudo-trigonal planar coordination environment consisting of one nitrogen from each ligand and one oxygen from a CO2CF3 anion. We note that the X-ray structure is well-reproduced by the calculations, if the CO2CF3 anions are involved in the molecular models (see ESI for details). The anion is a monodentate donor and does not bridge silver(I) ions, which is in contrast with the PF4 and OTs containing structures described below.

1-Ag-OTs crystallizes in the P-1 space group with two silver(I) complexes in the asymmetric unit. Here, the complex is a dimer consisting of two molecules of 1 and a cluster of four silver(I) ions bridged by four OTs anions (Figure 3b). The four nitrogen atoms, from two ligands of 1, coordinate to different silver(I) centers. Each of the silver(I) ions has a pseudo trigonal pyramidal coordination geometry occupied by three separate oxygens from three OTs anions and one nitrogen from ligand 1. The four OTs anions utilize one, two or three oxygens to coordinate to a single silver(I) ion or bridge between two or three different silver(I) ions.

1-Ag-PF4 crystallizes in the P21/n space group as a coordination polymer. Interestingly, even though AgPF6 was used in the crystallization process, electron density corresponding to a tetrahedral anion was observed and was best modeled as PF4. The coordination polymer is comprised of di-nuclear silver(I) complexes linked in a linear fashion by two bridging anions. Each complex is comprised of a dimer of 1 and the silver(I) centers are coordinated by two pyridine nitrogen atoms from different molecules of 1. One fluorine atom from two separate anions also coordinates to the silver centers resulting in a tetrahedral coordination geometry around each silver(I). Each anion also coordinates to an adjacent silver(I) complex linking the coordination polymer in the solid state.

The crystal structures highlight that 1 forms different dimeric complexes with silver(I) depending on the counter anion that is present. All three silver(I) complexes in the crystal structures deviate from the DFT calculations presented herein. Clearly, the anion plays an important role in the speciation of the silver(I) complexes. The anions were not computationally modeled in our present work. Unfortunately, due to their low stability, no crystals suitable for X-ray diffraction were obtained for the 1-I complexes. Thus, we turned to NMR spectroscopy to further elucidate the differences between the 1-Ag and 1-I complexes.

2.5 Solution Structure of [N⋯Ag⋯N]+ Complexes.

The 1H NMR spectra of the five silver(I) complexes, obtained in CD2Cl2 and shown in Figure 4, were broadened to various degrees depending on the coordination strength of the anion.28 The spectra of complexes possessing strongly coordinating anions, such as CO2CF3, OTs, and OTf, were not as broad compared to those of the weakly coordinating BF4 and PF6 complexes. The differences in the spectra could be explained by the strongly coordinating anions forming one well-defined geometry for their silver(I) complexes, whereas the weakly coordinating anions promote a dynamic mixture of several geometries. Alternatively, the weakly coordinating anions could promote the formation of larger aggregates, as the empty silver(I) coordination sites may allow for silver(I)-silver(I) interactions, which are known in the literature.29 The direct coordination of strongly coordinating anions has previously also been reported for analogous [bis(pyridine)silver(I)]+ complexes.26 The silver-silver interactions are further corroborated by the observation of several sets of signals at low temperature for the 1-Ag-BF4 complex (Figure S41, ESI). The flexibility of ligand 1 makes it possible to form silver(I) complexes with various geometries as compared to the conformationally restricted complexes reported previously.26

To assess the size of the complexes in solution, translational diffusion rates were acquired using 1H NMR detection, following previous protocols.15,26 The translational diffusion coefficients of 1-Ag-CO2CF3 (D = 7.49 × 10−10 m2/s), 1-Ag-OTf (D = 7.00 × 10−10 m2/s), and 1-Ag-OTs (D = 7.20 × 10−10 m2/s) were significantly lower than that of ligand 1 (D = 11.21 × 10−10 m2/s), indicating that these have 1.6-times larger molecular radii. This is in agreement with the dimeric geometry predicted for these complexes by DFT. The dimers were further supported by high-resolution mass spectrometry providing the m/z signal corresponding to complex [12 · Ag2]2+ for 1-Ag-BF4, 1-Ag-PF6, 1-Ag-OTf, 1-Ag-CO2CF3, and 1-Ag-OTs (ESI). Hence, the solution structure of the 1-Ag complexes shows a counterion dependent dynamic behavior, and are in agreement with the speciation computed by DFT and observed by X-ray.

2.6 Solution Structure of [N⋯I⋯N]+ Complexes.

1H NMR signals for all iodine(I)-centered complexes were slightly broadened, as compared to ligand 1 (Figure 5). 1H DOSY was measured to assess the size of 1-I complexes in solution. The translational diffusion coefficients D = 10.67 × 10−10 m2/s (1-I-BF4), D = 10.51 × 10−10 m2/s (1-I-PF6), D = 11.09 × 10−10 m2/s (1-I-OTf), D = 10.86 × 10−10 m2/s (1-I-OTs), and D = 10.65 × 10−10 m2/s (1-I-CO2CF3) were comparable to that of ligand 1, suggesting that these complexes are monomeric. Neither 1H NMR nor diffusion NMR indicates a counterion dependence of the structure of these 1-I complexes, which is in agreement with previous observations that the halonium ions of three-center [N⋯I⋯N]+ complexes do not coordinate anions.26

Our spectroscopic data suggests that the silver(I) complexes of 1 predominantly form dimers, whereas the iodine(I) complexes form monomeric species in solution. The former are enthalpically favored whereas the latter are entropically favored. The counterion does not have a direct effect on the structure of the 1-I complexes but it does have a significant influence on the 1-Ag complexes with distinct signs of aggregation in the presence of the non-coordinating anions. Furthermore, the counterion dependent formation of dimeric and polymeric 1-Ag complexes in the single crystal X-ray structures highlights the importance of the coordinating ability of the counterion on speciation. Computation at the DFT level suggests that the dimers for both 1-Ag and 1-I complexes are more stable than the monomeric alternatives. Deviation of computational and experimental observations have previously been reported for analogous [N⋯X⋯N]+ complexes.30,31 Here, it is most likely the consequence of the counterions not being involved in the computations.

This study demonstrates a subtle difference between silver(I) and iodine(I)-centered three-center, four-electron complexes. Such a difference between metal coordination bonds and halogen bonds is reported here for the first time. A deeper understanding of the main driving forces of halogen bonding, and its differences to other weak interactions, such as metal coordination, is expected to strengthen its applicability as an alternative supramolecular tool and provide new insights for the development of novel halogen bond-based catalysts.

We thank the Swedish Research Council (2016-03602), FORMAS (2017-01173), Magnus Ehrnrooth Foundation, the Finnish Cultural Foundation, and the Wenner-Gren Foundation (F2020-0003) for financial support. We thank Andreas Orthaber (Uppsala University) for access to an X-ray diffractometer. This project made use of the NMR Uppsala infrastructure, which is funded by the Department of Chemistry - BMC and the Disciplinary Domain of Medicine and Pharmacy. OBB and DAD acknowledge support by the Center for Biomolecular Structure and Dynamics CoBRE (NIH NIGMS grant P20GM103546). The X-ray crystallographic data for Ag-PF4 were collected using a Bruker D8 Venture, principally supported by NSF MRI CHE-1337908.

Experimental procedures, NMR spectra, details on X-ray crystallography and computational investigations. This material is available on https://doi.org/10.1246/bcsj.20200274.

Máté Erdélyi

Máté Erdélyi graduated at Semmelweis University, Hungary, and obtained his PhD in organic chemistry at Uppsala University, Sweden, 2004. Following postdoctoral research in physical organic chemistry (University of California, USA), NMR spectroscopy and structural biology (Max Planck Institute for Biophysical Chemistry, Germany), he initiated independent research at the University of Gothenburg, Sweden. He moved to Uppsala University in 2017, and carries out research on halogen bonding, NMR method development, natural product and medicinal chemistry.

Orion B. Berryman

Orion B. Berryman obtained his B.A. in chemistry from the University of New Hampshire. While studying anion-pi interactions and anion receptors he received his PhD in organic/inorganic chemistry from the University of Oregon. Following a postdoctoral stay at The Scripps Research Institute with Julius Rebek Jr. he started his independent career as a faculty member at the University of Montana where he is currently an associate professor and director of the Small Molecule X-ray Diffraction Core. His present research interests include halogen bonding and the self-assembly of anion binding foldamers.