Macrocyclic complexes based on [N⋯I⋯N]⁺ halogen bonds

Abstract

New 1–2 nm macrocyclic iodine(I) complexes prepared VIA a simple ligand exchange reaction manifest rigid 0.5–1 nm cavities that bind the hexafluorophosphate anion in the gas phase. The size of the cavities and the electrostatic interactions with the iodine(I) cations influence the anion binding properties of these macrocyclic complexes.

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The iodine(I) cation (aka iodenium ion) can be considered as an ‘‘ultra-polarized’’ iodine atom that can act as a very strong bis-halogen-bond donor by forming a three-center-four-electron (3c–4e) halogen bond with two Lewis bases (L) resulting in [L–I–L]A (A = anion) complexes¹ with the specific bonding character of the iodine(I) cation.² The 3c–4e halogen bond, viz. [N⋯I⋯N]⁺, is a robust silver(I)-like building block with enhanced linearity of the N⋯I⋯N bond, and thus has great potential as a construction unit for many intricate supramolecular structures. The iconic example of an iodine(I) complex is Barluenga's reagent,³ bis(pyridine)iodine(I) tetrafluoroborate [(py)₂I]BF₄, known in synthetic chemistry as an iodinating agent for aromatic electrophilic substitutions and aromatic amines, yet can also be used as an oxidizing agent.^4–9 However, probably due to the reactivity as an iodinating reagent, the incorporation of iodine(I) as a component in larger supramolecular systems like molecular capsules or cages,^10–13 rotaxanes,¹⁴ monomolecular helicates,¹⁵ and XOFs,¹⁶ has only recently been described. In addition to the “simple” symmetric¹ and asymmetric¹⁷ [L–I–L]A complexes several monomeric clamp-type iodine(I) complexes have been intensely studied by Erdélyi.^18–22 In one case an I⁺-clamp complex has been suggested to form a dimer, yet it was found to be unstable and experimentally detectable only at low temperatures (−40 °C).²³

Inspired by the known three ligands (L1–L3) and their dimeric silver(I) metallacycles,^24–26 [(AgL)₂]²⁺, and the previously successfully applied^{1,10–13,15–17} [N⋯Ag⋯N]⁺ → [N⋯I⋯N]⁺ cation exchange reaction, we envisaged that construction of the corresponding halogen-bonded macrocyclic bis-iodine(I) complexes [(IL)₂](PF₆)₂ (1–3, Scheme 1) could be achieved. The initial tries with the silver(I) metallacycles and elemental iodine did not proceed cleanly due to the possibility of the metallocycle to open during the exchange reaction and induction of subsequent side reactions, thus an alternative route, viz. a ligand exchange reaction previous applied by Dutton²⁷ for simpler iodine(I) complexes, was successfully used. Using a stable iodine(I) complex bis(1-methyl-1H-1,2,3-triazole) iodine(I) hexafluoro-phosphate ([I(mtz)₂]PF₆)²⁸ (see ESI†), and ligands L1–L3, the halogen-bonded iodine(I) macrocyclic complexes 1–3 were obtained with 79–87% yield.

Scheme 1 Ligands L1–L3 used and the target macrocycles 1–3.

The ¹H NMR analyses of 1 and 2 (Fig. 1) suggested, as expected, the formation of one highly symmetrical complex. The complexes (1 or 2) are kinetically stable and symmetric; the integrals for each of the protons on the ligand remain unchanged, and each peak remains sharp, indicating the formation of only one complex. The downfield shift of the signals (H_A, H_D and H_C) and the upfield shift of signal H_B for complex 1 as compared to those for L1 (Δδ = 0.05, 0.25, 0.13 and −0.06 ppm, respectively), and the downfield shift of the signals for complex 2 as compared to those for L2 (Δδ = 0.30, 0.27, 0.28 and 0.12 ppm, respectively), are characteristic of the iodine–ligand complexation.^17–19,29 The methyl groups in relation with the macrocyclic core result in three district conformations (up-down-up-down; up-up-down-down and all-up) for the methylimidazole complex 3. The ¹H NMR spectrum of 3 suggested there are two distinct complexes (Fig. S20, ESI†). The X-ray structures^26,30 of the silver(I) metallacycle from ligand 3 shows only the up-up-down-down conformation. Computational studies (see below and ESI†) of the three conformations indicate that the all-up is least stable, thus the ¹H NMR of 3 is interpreted to contain a 60 : 40 ratio of up-up-down-down (3a) and up-down-up-down (3b) conformations (see ESI†).

Fig. 1 Selected region of ¹H NMR spectra (500 MHz, CD₃CN, 298 K) for ligand L1 (a), macrocycle 1 (b), the ligand L2 (c) and macrocycle 2 (d).

The formation of stable iodine(I) complexes with N⋯I⋯N 3c–4e halogen bonds was also confirmed by the N-atom coordination shifts (Δδ¹⁵N_coord) of −90 to −110 ppm (Table 1) in the ¹H–¹⁵N HMBC NMR spectra. The two nitrogen atoms are directly involved in the N⋯I⋯N 3c–4e bond, which, in combination, results in large chemical shift changes.³¹ The values are comparable to the coordination shifts observed in similar iodine(I) complexes (Fig. S25, ESI†).^12,17,18

Table 1 The ¹⁵N chemical shifts and ¹⁵N coordination shifts for 1–3 (Δδ¹⁵N_coord = δ¹⁵N_complex – δ¹⁵N_ligand)

	L1/1	L2/2	L3/3a/3b
δ^15	−62.7/−173.3	−117.3/216.1	−120.1/−210.1/212.1
Δδ^15Ncoord	−110.6	−98.8	−90.5(3a)/−92.0(3b)

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In order to probe the size of the macrocycles in solution ¹H DOSY NMR spectra was measured in CD₃CN. The diffusion constants for complexes 1–3 are ca. two times smaller, evidencing discrete macrocycles two times larger in size than the ligands L1–L3 (Table S1, ESI†), confirming that these two complexes are dimeric, not monomeric or polymeric.

Despite rigorous attempts X-ray quality crystals of 1–3 were not obtained. Large basis set DFT calculations have been applied for the macrocycles 1–3 (Fig. 3 and Fig. S32, ESI†). The geometries of the optimized complexes have been compared with the X-ray structures of the corresponding silver(I) metallacycles retrieved from the CSD database. In general, the optimized geometries of the macrocyclic XB complexes (1–3) are very similar to the X-ray geometries of the corresponding silver(I) metallacycles.

The main structural difference is that the N⋯I⋯N angles in 1–3 are more linear than the N⋯Ag⋯N analogues. Moreover, the intra-complex I⁺···I⁺ distances are shorter than the Ag⁺···Ag⁺ distances in complexes 1 and 2 and longer in complex 3 (see Fig. 2), their variations are very likely caused by the different packing and anion–cation interactions in the solid-state of the silver(I) metallacycles.

Fig. 2 Optimized geometries of compounds 1 (a), 2 (b) and 3a (c) at the M06-2X/def2TZVp level of theory. The X-ray structures of the corresponding Ag(I) metallacycles (CSD refcodes OSASEH (b) and ECALEA (d) and HIZPEN (f)).

The stoichiometries and structures of the complexes were further verified using electrospray ionization ion mobility mass spectrometry (ESI-IMMS). In gas phase, the complexes were observed to complex the PF₆⁻ anion into the cavity of the macrocycle and ions [1-PF₆]⁺, [2-PF₆]⁺ and [3-PF₆]⁺ appeared in spectra with high abundance (ESI,† Fig. S28–S30 and Fig. 3.) The MS/MS analysis also confirmed the composition as [2L + 2I + PF₆]⁺ and showed structure-related dissociation of macrocycles through consecutive eliminations of IPF₆ or HPF₆ and ligands L1, L2 or L3.

Fig. 3 (+)ESI-QTOF mass spectrum (a) 1, (b) 2 and (c) 3 in MeCN. Insets show IM-TOF arrival time distributions for ions [C-PF6]⁺.

The correlation between theoretical and experimental structures was further analyzed by ion-mobility mass spectrometry experiments.³² To visualize the IM-MS data, [1,2,3-PF6]⁺ complexes were DFT-optimized (Fig. 4). The calculations show that the cavity in 2 or 3 just suitable for the PF₆⁻ anion which fits very well inside the cavity, as evidenced by the optimized geometries of the host–guest complexes. An interesting combination of non-covalent interactions is formed. The complex [2-PF₆]⁺ manifests two anion–π interactions, due to the presence of two electron-deficient tetrafluorophenyl rings in the macrocycle (marked as red dashed lines in Fig. 4a). In fact, two fluorine atoms of the anion point to the center of the electron-deficient rings (distance 3.16 Å). Additional C_sp2–H⋯F HBs (2.37 Å) and electrostatic forces I⁺⋯PF₆⁻ firmly hold the guest inside the cavity. The orientation of the anionic guest is different in [3-PF₆]⁺ because the aromatic rings of the macrocycle are electron-rich. In this case the four fluorine atoms of the anion point towards the methyl groups, establishing multiple C_sp³–H⋯F contacts (distances 2.48–2.54 Å). The [3-PF₆]⁺ host–guest complex is further stabilized by I⁺⋯PF₆⁻ ion pair interactions. The IM-MS arrival time distributions (ATDs) showed single drift peaks for the host–guest complexes [2-PF₆]⁺ and [3-PF₆]⁺. The experimentally observed collision cross section values using He as a drift gas (^DTCCS_He) for these ions were 184.4 Ų and 182.3 Ų, respectively. The values show nice correlation (<1.9% difference) with theoretical CCS values (^TMLJCCS_He) calculated on basis of DFT-optimized structures (Table S3, ESI†). This comparison between theoretical and experimental results verifies macrocyclic structure, analogues to Ag⁺ complexes, also in the gas phase. This further suggests that the PF₆ anion act as a guest and is located inside the macrocycle. The two conformers observed in ¹H NMR spectra for 3 could not be resolved by IM-MS, because the theoretical ^TMLJCCS_He values for 3a and 3b differ only by 0.98 Ų (typically ∼1% difference is expected to be resolved with ultra-high resolving power instruments).³² The IM drift peak for [3-PF₆]⁺ has, however, clearly decreased resolution (R_FWHM for [3-PF₆]⁺ is only 29.7 whereas for [2-PF₆]⁺ R_FWHM = 46.3), which often indicates several closely related, unresolved conformers.

Fig. 4 Optimized structures of host–guest complexes of macrocycles 2 (a) and 3 (b) with the PF₆⁻ anion at the M06-2X/def2-TZVP level of theory.

The ATD for much larger [1-PF₆]⁺ surprisingly shows distribution of IM drift peaks ranging from 196.6 to 237.8 Ų. The DFT optimization confirm, that the cavity in 1 is much larger than the size of PF₆ anion, allowing different locations for a guest within the cavity (see Fig. S32a (ESI†) for one possible host–guest complex). To study this, the structures of endo and exo complexes for [1-PF₆]⁺ were calculated, resulting in ^TMLJCCS_He values of 228.8 and 231.8 Ų, respectively. Whereas in [2-PF₆]⁺ and [3-PF₆]⁺ the anion has a tight fit, the complexation of PF₆⁻ into the larger cavity of [1-PF6]⁺ results in less specific interactions with the cavity walls and offers larger degrees of freedom for the spatial location of the guest. We conclude that the multiple IM peaks originate from the different locations of loosely bound PF₆⁻ counter anion. Also according to the MS measurements the [1-PF₆]⁺ complex is less stable (has lower interaction energy), which is reflected in MS/MS spectra (collision induced dissociation, CID) showing more dissociation and lower relative intensity for [1-PF₆]⁺ precursor ion when compared with the [2-PF6]⁺ and [3-PF6]⁺ precursor ions.

In summary, we have demonstrated a simple preparation of three new iodine(I)-based macrocycles via ligand exchange reaction, and studied their structures and host–guest behavior using ¹H and ¹H–¹⁵N HMBC and DOSY NMR, IM-MS and theoretical calculations. Further studies of these systems are underway in our laboratory. The simple preparation route to the previously unreported iodine(I) macrocycles might provide a way to construct iodine(I)-based mechanically interlocked molecules.

We gratefully acknowledge financial support from the Academy of Finland (K. R. grant no. 317259), the MICIU/AEI of Spain (A. F. project CTQ2017-85821-R FEDER), and the University of Jyvaskyla, Finland.

Conflicts of interest

There are no conflicts to declare.

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Footnote

† Electronic supplementary information (ESI) available: Experimental procedures, compounds characterization, DFT calculations. See DOI: 10.1039/d1cc05616f

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