Methylresorcinarene: a Reaction Vessel to Control the Coordination Geometry of Copper(ii) in Pyridine N-oxide Copper(ii) Complexes

Pyridine and 2-picolinic acid N-oxides form 2 : 2 and 2 : 1 ligand : metal (L : M) discrete L2M2 and polymeric complexes with CuCl2 and Cu(NO3)2, respectively, with copper(ii) salts. The N-oxides also form 1 : 1 host-guest complexes with methylresorcinarene. In combination, the three components form a unique 2 : 2 : 1 host-ligand-metal complex. The methylresorcinarene acts as a reaction vessel/protecting group to control the coordination of copper(ii) from cis-see-saw to trans-square planar, and from octahedral to square planar coordination geometry. These processes were studied in solution and in the solid state via(1)H NMR spectroscopy and single crystal X-ray diffraction.


Introduction
The construction of supramolecular architectures utilizing a variety of weak interactions has potential applications in materials science and biomimetic chemistry. 1The challenge of constructing exotic supramolecular architectures with function from small-molecule building blocks requires a better understanding to design strategies. 2 Resorcinarenes are an extensively studied phenolic group containing macrocyclic compounds. 3Easy syntheses, bowl-shape and electron-rich interior cavity are assets strongly associated with resorcinarenes, making them a useful component in host-guest inclusion chemistry. 3The size and the electronic nature of the guest molecules are important for determining the final structures and morphologies of the supramolecular architectures. 3 Consequently, different guests have templated assemblies such as open inclusion complexes, 4 dimeric and hexameric capsules, 5 as well as nanotubes. 6he concept of metallosupramolecular chemistry is based on the formation of discrete assemblies or coordination polymers through bridging organic ligands and metals. 7Pyridine N-oxides are typical oxygen atom transfer reagents, routinely used in the syntheses of high-valent transition metal centers, lanthanide and actinide oxo complexes. 8Copper plays an important role in redox chemistry with application in catalysis 9 and biology. 10There are multiple reports of different com-plexes and architectures formed between copper and pyridine N-oxide with applications such as in catalysis, 11 as magnetic conducting materials, 12 and with cytotoxic characteristics. 13he quest for potential applications of resorcinarenes is a continuous goal for researchers working in this area.There is a need to explore the bowl-shaped interior cavity of electron rich resorcinarenes as an essential feature, treating them as a reaction vessel or a protecting group tuning specific reactions.The aromatic ring of pyridine N-oxides through π⋯π interactions can be bound by the electron-rich resorcinarenes.There are several reports of complexes formed between calix [4]arenes 14 and cavitands 15 with pyridine N-oxides.Atwood et al. 16 reported nano-sized spherical and helical tubular structures formed through hydrophobic and numerous noncovalent interactions, such as metal-ligand coordination, π⋯π stacking, hydrogen bonding, and van der Waals forces associated with p-sulfonatocalix [4]arene, pyridine N-oxide and lanthanide nitrate.
In the study described herein, we explore the electron-rich interior cavity of methylresorcinarene 1 (Fig. 1) as a host for pyridine N-oxides 2-3 to form unique 2 : 1 ligand-metal N-oxide Cu II square planar products.In the process, methylresorcinarene acts as a protecting group creating steric hindrance for N-oxide coordination, thus changing its coordination mode and the coordination environment of Cu II products.These processes were studied in solution and in the solid state via 1 H NMR spectroscopy and single crystal X-ray diffraction analyses.

Results and discussion
4][5][6] In methylresorcinarenes, the electron donating methyl groups increase the electron density of the aromatic rings and thus increase their affinity towards electron deficient guest compounds.The electron push and electron pull nature of the negatively charged oxygen towards the aromatic ring in pyridine N-oxides makes these compounds a unique class of guest molecules, and they act as either electron rich or poor guest molecules with respect to the approaching reagents.Herein, for a π-electron rich receptor, pyridine N-oxide adopts a π-electron deficient system to exhibit π⋯π interactions.Also, the presence of hydroxyl groups in methylresorcinarene and oxygen in pyridine N-oxide makes it a suitable composite for hydrogen bond interactions between the host and the guest.With this prior knowledge of their behaviour towards metal coordination, we started to investigate the host-guest chemistry systematically, starting with solution based studies to inspect such evidence.

Host-guest complexation
We recently reported the 1 H NMR complexation studies of pyridine N-oxide 2 and methylresorcinarene 1 with an association constant of log K = 1.8157 ± 0.0171. 17A 1 : 1 mixture of methylresorcinarene 1 and pyridine N-oxide 2 in CD 3 OD at 303 K showed significant upfield shifts of the pyridine N-oxide 2 aromatic protons.The most intense shift of 0.62 ppm was observed for the para-protons, thus confirming its location deep in the cavity of the host. 17The generally large shifts of the guest signals highlight the shielding effects of the aromatic rings of the host 1. 18 The use of the carboxylic acid group at the ortho-position of pyridine N-oxide and its electron withdrawing nature render the aromatic ring further electron deficient.This fact is highlighted by the larger shifts of the 2-picolinic acid N-oxide protons upon complexation with methylresorcinarene 1 (Fig. 2) as compared with the pyridine N-oxide 2. Chemical shift changes greater than 1 ppm are observed for the para-(1.22ppm) and meta-(1.10ppm) protons.Again, the large shift of the para-protons also suggests the guest located deep in the cavity of the host.
To further study these systems in the solid state, single crystals suitable for X-ray analysis were obtained by mixing the respective methanol solutions of 1, 2 and 1, 3 to give 1 : 1 complexes of host 1 + pyridine N-oxide (I) and host 1 + 2-picolinic acid N-oxide (II), respectively, as shown in Fig. 3. Complex I crystallizes in the triclinic space group P1 ˉwith a 1 : 1 hostguest ratio, together with three water molecules in the asymmetric unit.Pyridine N-oxide 2 sits inside the cavity at a height of ca.3.09 Å from the centroid of the lower rim carbon atoms, and stabilizes by π⋯π interactions 19 with one of the host aromatic rings at a centroid-to-centroid distance of 3.643 Å.In addition, the meta-and para-hydrogens of pyridine N-oxide 2 are stabilized with C-H⋯π (centroid) interactions at distances of 2.684 Å and 3.040 Å, respectively, as shown in Fig. 3a The crystal structure of II was solved in the triclinic space group P1 ˉ, and the asymmetric unit contains a 1 : 1 host-guest complex ratio.2-Picolinic acid N-oxide 3 sits deeper inside the cavity than pyridine N-oxide 2 at a depth of ca.2.58 Å, stabilized by π⋯π interactions with one of the host aromatic rings at a centroid-to-centroid distance of 3.704 Å.As shown in Fig. 3c As shown in Fig. 3a and b, the C-H⋯π interactions significantly contribute and support the 1 H NMR shift changes.The short C-H⋯π distances in II than in I explains the delocalization of shared π-electrons with the electron withdrawing -COOH group, followed by the formation of a stable six-membered ring by intramolecular hydrogen bonding.The large shifts of c-and d-protons of the guest 3 also explains the pres-

Metal complexation
NMR spectroscopy is a useful tool for studying the structural and magnetic properties of Cu II coordination compounds. 20he slow electronic relaxation of Cu II ions mostly results in large line widths and poor resolution, making the interpretation of spectra of Cu II complexes almost impossible.This paramagnetic effect is stronger for protons in close proximity to the copper ions. 20he 1 H NMR spectra of a 1 : 1 mixture of pyridine N-oxide 2 and CuCl 2 show only one broad signal around 9.2 ppm within the 0-100 ppm window (Fig. 4c).From X-ray crystal structures (Fig. 3), the guest is tilted towards a phenyl ring of the host 1 to maximize π⋯π interactions.This orientation of the pyridine N-oxide creates steric hindrance for bidentate coordination, which will tune the coordination geometry of the Cu II .
A series of 1 H NMR experiments were done to test this hypothesis.In the experiment, several samples were prepared consisting of the host 1, the N-oxides 2-3, CuCl 2 and Cu(NO 3 ) 2 •3H 2 O salts.The 1 H NMR spectrum of the mixture containing 1, 2 and CuCl 2 shows a substantial increase of 0.84 ppm of the broad pyridine N-oxide signals at 8.3 ppm (Fig. 4b).This upfield shift is either consistent with shielding of the guest signals by the phenyl rings of the host 1 or the formation of a different product.The pyridine N-oxide 2 signals are broadened as a result of the slow relaxation of the Cu II ions, while all the methylresorcinarene 1 signals are observed.The upfield shifts of the methylresorcinarene 1 signals support the formation of a host-guest complex with the Cu II coordinated pyridine N-oxides (Fig. 4).
The 1 H NMR spectrum of a 1 : 1 mixture of 2-picolinic acid N-oxide 3 and Cu(NO 3 ) 2 •3H 2 O was analogous to the pyridine N-oxide 2, with a single broad signal around 10.5 ppm within the 0-100 ppm window (Fig. S6 †).This larger downfield shift is as a result of the more electron-deficient product.The single broad signal of the 2-picolinic acid N-oxide 3 disappears in the combination of 1, 3 and Cu(NO 3 ) 2 •3H 2 O, also suggesting  shielding or the formation of a different product.However, upfield changes of the methylresorcinarene 1 signals are analogous to those observed with the pyridine N-oxide 2, hinting at a similar host-guest product (Fig. S6 †).
To unambiguously confirm the structures of the hostligand-metal complexes, solid state analyses via single crystal X-ray diffraction were done.Reactions of pyridine N-oxide 2 and CuCl 2 and between 2-picolinic acid N-oxide 3 and Cu(NO 3 ) 2 •3H 2 O resulted in a discrete structure III (Fig. 5a) and 1D polymeric self-assembly V (Fig. 5d), respectively.Complex III crystallized in the monoclinic space group P2 1 /c with a 1 : 1 ligand to metal ratio.The µ 2 -O,O pyridine N-oxide 2 bridges Cu1 and Cu1a, with Cu II in the Cl 2 O 2 coordination sphere, and have adopted cis-see-saw III 21 (τ 4 = 0.34) 22 geometry.
On the other hand, complex V is a 1D polymeric structure (Fig. 5d and S9 †) with octahedral Cu II in the O 4 coordination sphere.Complex V crystallized in the monoclinic space group P2 1 /c, the asymmetric unit contains one 2-picolinic acid N-oxide 3 chelating half a copper in a 2 : 1 ligand to metal ratio.A CCDC search related to III (CSD Refcodes: CUCPYO, CUCPYO11 and CUCPYO12) 21 and V (CSD Refcode: SIJRIN) 23 revealed three and one hits, respectively, which are synthesized under different conditions.
The π⋯π and C-H⋯π interactions between the host 1 and the guest molecules 2, 3 engendered a steric effect, thus causing a dramatic change in the coordination sphere around Cu II , which is different from complexes III and V. 20,22 As a consequence, the bidentate pyridine N-oxide 2 in the L 2 M 2 host free complex now adopts a monodentate coordination mode with trans-L 2 M geometry in IV (Fig. 5).The coordination sphere of the Cu II changes from cis-see-saw in III to transsquare planar geometry in IV.The coordination sphere of square planar Cu II in IV is tightly held and stabilized by -OH⋯O (2.803 Å, ∠O-H⋯O 138.57°) and -OH⋯Cl (3.127 Å, ∠O-H⋯Cl 163.33°) interactions (Fig. S7b †).Interestingly, the N-oxide in IV preserves its bidenticity through hydrogen bonding with a methanol molecule (Fig. S7b †).The Cu II in VI is apically stabilized by water molecules at a Cu⋯O distance of 2.740 Å. Square planar geometries, especially Cu II ions, compete with aqua ligands for binding and such a preference often leads to ligand field stabilization, either by strong coordination 24 or by weak interactions (Fig. S8b †).

Conclusions
In summary, the interior cavity of methylresorcinarene 1 through π⋯π, CH⋯π and hydrogen bond interactions templates the formation of a unique 2 : 2 : 1 (host-ligand-metal) complex with N-oxides 2-3 and Cu II salts (CuCl 2 and Cu-(NO 3 ) 2 •3H 2 O).The coordination geometry of the Cu II changes from cis-see-saw (III) to trans-square planar (IV), and from octahedral (V) to square planar (VI) products.With pyridine N-oxide 2, the anion (Cl − ) completes the coordination geometry.Introducing a chelating carboxylic acid functional group in the ortho-position of the pyridine N-oxide 3 led to a similar coordination compound.Though the Cu II ion retains the same geometry, the carboxylic acid group completes the coordination geometry with the nitrate anion as a passive spectator.Despite the paramagnetic nature of Cu II , the host signals could be monitored to confirm the complexation in solution via 1 H NMR spectroscopy.Single crystal X-ray diffraction studies unambiguously confirmed the formed products and their specific coordination geometries.This work highlights the usefulness of the resorcinarene framework as a reaction vessel for pyridine N-oxide copper complexes in tuning specific Cu II coordination sphere products governed by several weak interactions.
. The N-O group is a bidentate hydrogen bond acceptor for two outof-cavity water molecules at (N-O) guest ⋯O-H distances of 2.638 Å [∠(N-O) guest ⋯O-H, 135.66°] and 2.635 Å [∠(N-O) guest ⋯O-H, 163.69°].The hydrogen bonding between the water molecules and the N-O group of pyridine N-oxide plays an important role in bringing two 1 : 1 host-guest assemblies closer.As a result, the oxygens of N-O groups are at a distance of ca.6.032 Å, which provided us an insight to glue the N-O groups of the guests with metals (Fig. S3a †).

Fig. 2
Fig. 2 I H NMR spectra (CD 3 OD, 303 K) of a 30 mM solution of(a) 1, (b) a 1 : 1 mixture of 1 and 3, and (c) 3. The chemical shift changes are in ppm.Stars represent water molecules present in the complex (see Fig.3).

Fig. 3
Fig. 3 (a) Representation of two 1 : 1 host-guest complexes of host 1 + pyridine N-oxide (I), and (b) a colour coded CPK model of complex I. (c) Representation of two 1 : 1 host-guest complexes of host 1 + 2-picolinic acid N-oxide (II), and (d) a colour coded CPK model of complex II.The C-H⋯π interactions are shown by black broken lines from hydrogens of aromatic rings of N-oxide to the centroid of host aromatic rings.

Fig. 5
Fig. 5 (a) Ball and stick representation of complex III.(b) 2 : 2 : 1 Host-guest metal complex of IV.(c) Colour coded CPK model of complex IV.(d) Ball and stick representation of complex V. (e) 2 : 2 : 1 Host-guest metal complex of VI. (f ) Colour coded CPK model of complex VI.The insets of the N-oxide-copper complexes inside the hosts are shown for clarity.The C-H⋯π interactions are shown by the black broken line from hydrogens of aromatic N-oxide guest molecules to the centroid of the host aromatic rings.