The Formation of a Unique 2D Isonicotinate Polymer Driven by Cu(II) Aerobic Oxidation

The isolation and structural characterization of a unique Cu(II) isonicotinate (ina) material with 4-acetylpyridine (4-acpy) is provided. The formation of [Cu(ina)2(4-acpy)]n (1) is triggered by the Cu(II) aerobic oxidation of 4-acpy using O2. This gradual formation of ina led to its restrained incorporation and hindered the full displacement of 4-acpy. As a result, 1 is the first example of a 2D layer assembled by an ina ligand capped by a monodentate pyridine ligand. The Cu(II)-mediated aerobic oxidation with O2 was previously demonstrated for aryl methyl ketones, but we extend the applicability of this methodology to heteroaromatic rings, which has not been tested so far. The formation of ina has been identified by 1H NMR, thus demonstrating the feasible but strained formation of ina from 4-acpy in the mild conditions from which 1 was obtained.


Introduction
The discovery of graphene foregrounded the outbreak of 2D materials, which was triggered by their fascinating electrochemical, mechanical, and optical properties. Their better performance over 0D and 1D materials fostered the rapid development of 2D-based technologies for electrochemical devices, renewable energy storage, and production or for catalysis. Especially in these fields, the aim is, per se, to encounter clean, renewable, and inexpensive sources, so Cu(II)-based materials were expected to be one of the most promising candidates since Cu(II) combines high natural abundance with low toxicity [1].
Within this frame, our group has previously reported the synthesis and characterization of Cu(II) complexes with carboxylic acids and pyridine derivatives [2][3][4]. During the assays to further extend this research with 4-acetylpyridine (4-acpy), we performed its reaction with Cu(NO 3 ) 2 ·3H 2 O in acetonitrile (ACN) as a solvent. From this reaction, the serendipitous formation of single crystals, which were isolated and characterized, revealed the formation of an isonicotinate (ina) ligand, which further coordinated to the Cu(II) center and fostered the formation of complex [Cu(ina) 2 (4-acpy)] n (1). Therefore, in this contribution, we present the serendipitous formation of a Cu(II) isonicotinate (ina) material starting from Cu(NO 3 ) 2 ·H 2 O and 4-acpy.
Interestingly, the elucidation of its crystal structure revealed the arrangement of a 2D isonicotinate material. Indeed, isonicotinic acid (ina) has been vastly employed as an archetypal linker for the construction of extended networks. In particular, Cu(II) isonicotinates have presented from 0D to mostly 3D structures, benefiting from the great variety of coordination modes of ina ranging from monodentate to bridging. Within this plethora of available structures, Cu(II) ions mainly present square pyramidal geometry and lead to the assembly of highly stable 3D nets [5] featured by [Cu(ina) 2 ] n [6]. This  (4-acpy] n (1) To an ACN solution (6 mL) of Cu(NO 3 ) 2 ·3H 2 O (12.0 mg, 0.050 mmol), liquid 4-acpy (23 µL, 0.317 mmol) was added. The reaction was stirred under reflux for 16 h and then was transferred to a vial and left to slowly evaporate for 1 month. After this period, suitable green crystals of 1 were grown.

X-ray Crystallographic Data
A green prism-like specimen of 1 was used for the crystallographic data collection. The X-ray intensity data were measured on a D8 Venture system equipped with a multilayer monochromator and a Mo microfocus. The frames were integrated with the Bruker SAINT software package, using a narrow-frame algorithm. The integration of the data with a 0.70 Å resolution gave an average redundancy of 7.101, a completeness of 99.7%, and an R sig of 4.05%. From this integration, 3135 (82.33%) independent reflections were greater than 2σ(|F| 2 ).
The structure was solved and refined using the Bruker SHELXTL Software Package (version-2018/3) [29]. The final cell constants and volume are based upon the refinement of the XYZ-centroids of reflections above 20 σ(I). Data were corrected for absorption effects using the multi-scan method (SADABS). Crystal data and relevant details of structure refinement are reported in Table 1. The entire X-ray data of 1 can be found via the CCDC in .cif format, using the code 2252448. The X-ray structure was worked with Mercury 4.3.1 software, and molecular graphics were rendered using the POV-Ray image package [30]. Color codes used for the molecular graphics are orange roughy (Cu), red (O), light blue (N), grey (C) and white (H). The geometry evaluation of the Cu(II) center in the complex has been performed using version 2.1 of SHAPE [31] software, which is based on the low continuous-shape measure (CShM) value S [32]. It is a generalizable structural descriptor used to quantitatively evaluate distortion in terms of symmetry and distance from any ideal geometry. The corresponding atomic coordinates have been directly extracted from .cif data and the S values have been computed for any potential geometric accommodation within the corresponding coordination number five: vOC-5 = vacant octahedron; TBPY-5 = trigonal bipyramid; SPY-5 = square pyramid; JTBPY-5 = Johnson trigonal bipyramid.

Synthesis and General Characterization
The complex [Cu(ina) 2 (4-acpy)] n was synthesized by mixing in ACN the Cu(NO 3 ) 2 ·3H 2 O and the 4-acpy ligand in a 1:6 molar ratio, stirring under reflux, and then leaving it to stand for a month (Scheme 1). During this period, suitable green crystals of 1 were grown. The product was characterized by elemental analysis (EA), FTIR-ATR spectroscopy, and single-crystal X-ray diffraction. The geometry evaluation of the Cu(II) center in the complex has been performed using version 2.1 of SHAPE [31] software, which is based on the low continuous-shape measure (CShM) value S [32]. It is a generalizable structural descriptor used to quantitatively evaluate distortion in terms of symmetry and distance from any ideal geometry. The corresponding atomic coordinates have been directly extracted from .cif data and the S values have been computed for any potential geometric accommodation within the corresponding coordination number five: vOC-5 = vacant octahedron; TBPY-5 = trigonal bipyramid; SPY-5 = square pyramid; JTBPY-5 = Johnson trigonal bipyramid.

Catalytic Conversion
As previously mentioned, the aerobic oxidation of aromatic methyl ketones to carboxylic acids using Cu(II) as the catalyst has been previously reported, but no examples have been found using the analogous heteroaromatic molecules. After the obtention of complex 1, we tried to follow the conversion from 4-acpy to ina by 1 H NMR spectroscopy.
To this aim, we tested the oxidation of 4-acpy to ina, modifying the precursor, the solvent, and the O 2 pressure. These results have been summarized in Table 3.
As a general procedure adapted from [27], 0.100 mmol of the Cu(II) salt (24.16 mg of Cu(NO 3 ) 2 ·3H 2 O or 19.96 mg of Cu(OAc) 2 ·H 2 O) and 0.6 mmol of 4-acpy (68 µL) were placed in a vial and dissolved in either 2 mL of ACN or DMF, and the resulting dark blue solution was degassed. Then, the vials were filled with 2.1 bars of O 2 pressure, sealed, and put in the furnace at 120 • C for 18 h. Then, the reaction crude was dried and dissolved in DMF-d 7 or ACN-d 3 for the 1 H NMR experiments.

Catalytic Conversion
As previously mentioned, the aerobic oxidation of aromatic methyl ketones to carboxylic acids using Cu(II) as the catalyst has been previously reported, but no examples have been found using the analogous heteroaromatic molecules. After the obtention of complex 1, we tried to follow the conversion from 4-acpy to ina by 1 H NMR spectroscopy.
To this aim, we tested the oxidation of 4-acpy to ina, modifying the precursor, the solvent, and the O2 pressure. These results have been summarized in Table 3.
As a general procedure adapted from [27], 0.100 mmol of the Cu(II) salt (24.16 mg of Cu(NO3)2·3H2O or 19.96 mg of Cu(OAc)2·H2O) and 0.6 mmol of 4-acpy (68 µL) were placed in a vial and dissolved in either 2 mL of ACN or DMF, and the resulting dark blue solution was degassed. Then, the vials were filled with 2.1 bars of O2 pressure, sealed, and put in the furnace at 120 °C for 18 h. Then, the reaction crude was dried and dissolved in DMF-d7 or ACN-d3 for the 1 H NMR experiments.
First, aiming to demonstrate the feasibility of the catalytic conversion from 4-acpy to ina under similar experimental conditions from which 1 was isolated, the reaction between Cu(NO3)2·3H2O and 4-acpy was carried out in ACN under autogenous pressure at 120 °C for 18 h. Reactions were conducted using a closed vessel based on previous examples, evincing a boost in the reaction rate to achieve faster conversion [27].
The 1 H NMR in ACN-d3 of the resulting products revealed the recovery of 4-acpy and the mixtures of the corresponding aldehyde (4-formylpyridine, 4-fopy) and ina, therefore verifying that the Cu(II) catalytic oxidation of 4-acpy to ina is attainable (Figure 3a). Then, to further extend these results, we scrutinized different synthetic conditions to evaluate this process. To this end, two different solvents were employed: ACN and DMF. It should be mentioned that reactions performed in DMF resulted in the recovery of 4-acpy without any trace of 4-fopy nor ina, regardless of the Cu(II) precursor or the addition of 2.1 bars of O2 pressure (S.I: Figure S2). In addition, the use of Cu(OAc)2·H2O in ACN leads to the

Conclusions
We reported, for the first time, the assembly of a Cu(II) isonicotinate bearing a 2D layered structure holding a monodentate pyridine derivative, the 4-acpy ligand. The formation of ina has been traced back, resulting in the identification of the Cu(II) catalytic oxidation of 4-acpy using dioxygen as the oxidant. Thus, we extended the covering of the Cu(II)-driven oxidation of methyl ketones to a heteroaromatic molecule, suggesting an analogous pathway to the one followed by its aryl counterparts. The use of Cu(NO3)2·3H2O without O2 pressure or Cu(OAc)2·H2O at 2.1 bars of O2 provided a less efficient conversion, leaving unreacted 4-acpy, which probably drove the arrangement of 1. Similarly to the analogous reactions with aryl methyl ketones, the best results were garnered using ACN under an O2 pressure of 2.1 bars at 120 °C for 18h, from which ina was First, aiming to demonstrate the feasibility of the catalytic conversion from 4-acpy to ina under similar experimental conditions from which 1 was isolated, the reaction between Cu(NO 3 ) 2 ·3H 2 O and 4-acpy was carried out in ACN under autogenous pressure at 120 • C for 18 h. Reactions were conducted using a closed vessel based on previous examples, evincing a boost in the reaction rate to achieve faster conversion [27].
The 1 H NMR in ACN-d 3 of the resulting products revealed the recovery of 4-acpy and the mixtures of the corresponding aldehyde (4-formylpyridine, 4-fopy) and ina, therefore verifying that the Cu(II) catalytic oxidation of 4-acpy to ina is attainable (Figure 3a). Then, to further extend these results, we scrutinized different synthetic conditions to evaluate this process. To this end, two different solvents were employed: ACN and DMF. It should be mentioned that reactions performed in DMF resulted in the recovery of 4-acpy without any trace of 4-fopy nor ina, regardless of the Cu(II) precursor or the addition of 2.1 bars of O 2 pressure (S.I: Figure S2). In addition, the use of Cu(OAc) 2 ·H 2 O in ACN leads to the recovery of 4-acpy and mixtures of 4-fopy and ina (Figure 3b), yielding a similar result to that of Cu(NO 3 ) 2 ·3H 2 O without O 2 pressure.  Interestingly, employing Cu(NO 3 ) 2 ·3H 2 O and 4-acpy in ACN at 2.1 bars of O 2 pressure and heating up to 120 • C for 18h were found to be the best experimental conditions since only ina has been identified and no traces of additional products are present (Figure 3c). This is in agreement with the previous results with aromatic methyl ketones [27]. It should be mentioned that, from this reaction, a blue powder was isolated. After the filtration of the reaction crude and washing with 10 mL of DMF, the remaining solid was identified as [Cu(ina) 2 (H 2 O] n (S.I: Figure S3). This agrees with the two requirements needed to achieve the formation of 1: the gradual formation of the ina ligand and a sufficient amount of 4-acpy that remains unreacted. Thus, it is reasonable to suggest that the heteroaromatic analogue follows the same catalytic pathway [28], and the presence of 4-fopy is due to the incomplete conversion of 4-acpy into ina (Scheme 2). tified as [Cu(ina)2(H2O]n (S.I: Figure S3). This agrees with the two requirements needed to achieve the formation of 1: the gradual formation of the ina ligand and a sufficient amount of 4-acpy that remains unreacted. Thus, it is reasonable to suggest that the heteroaromatic analogue follows the same catalytic pathway [28], and the presence of 4-fopy is due to the incomplete conversion of 4-acpy into ina (Scheme 2). Therefore, Cu(NO3)2·3H2O can oxidize 4-acpy to ina even without O2 pressure, despite having the worst performance. Among the palette of oxidative reactions from methyl ketones with Cu(II), α-oxygenation to carboxylic acids and C-C bond cleavage to aldehydes can occur in similar conditions. The outcome is mainly biased by the strong dependence of the catalytic performance on the Cu(II) counterion. In this case, and as previous catalytic studies have already noticed, the use of Cu(OAc)2·H2O as the catalyst led to small quantities of the corresponding aldehyde [25]. Similarly, the absence of O2 pressure with Cu(NO3)2·3H2O also yielded mixtures of 4-fopy and ina, which reflects the need for O2 to boost the transformation into ina.
It should be noted that the decreased catalytic activity from Cu(OAc)2·H2O with respect to Cu(NO3)2·3H2O has already been reported and can be attributed to the decreased availability of Cu(II) ions that remain coordinated to the acetate ions. Similarly, the conversion of 4-acpy can be hindered by the coordination to the Cu(II) ions in contrast to aryl methyl ketones. Therefore, Cu(NO 3 ) 2 ·3H 2 O can oxidize 4-acpy to ina even without O 2 pressure, despite having the worst performance. Among the palette of oxidative reactions from methyl ketones with Cu(II), α-oxygenation to carboxylic acids and C-C bond cleavage to aldehydes can occur in similar conditions. The outcome is mainly biased by the strong dependence of the catalytic performance on the Cu(II) counterion. In this case, and as previous catalytic studies have already noticed, the use of Cu(OAc) 2 ·H 2 O as the catalyst led to small quantities of the corresponding aldehyde [25]. Similarly, the absence of O 2 pressure with Cu(NO 3 ) 2 ·3H 2 O also yielded mixtures of 4-fopy and ina, which reflects the need for O 2 to boost the transformation into ina.
It should be noted that the decreased catalytic activity from Cu(OAc) 2 ·H 2 O with respect to Cu(NO 3 ) 2 ·3H 2 O has already been reported and can be attributed to the decreased availability of Cu(II) ions that remain coordinated to the acetate ions. Similarly, the con-version of 4-acpy can be hindered by the coordination to the Cu(II) ions in contrast to aryl methyl ketones.

Conclusions
We reported, for the first time, the assembly of a Cu(II) isonicotinate bearing a 2D layered structure holding a monodentate pyridine derivative, the 4-acpy ligand. The formation of ina has been traced back, resulting in the identification of the Cu(II) catalytic oxidation of 4-acpy using dioxygen as the oxidant. Thus, we extended the covering of the Cu(II)-driven oxidation of methyl ketones to a heteroaromatic molecule, suggesting an analogous pathway to the one followed by its aryl counterparts. The use of Cu(NO 3 ) 2 ·3H 2 O without O 2 pressure or Cu(OAc) 2 ·H 2 O at 2.1 bars of O 2 provided a less efficient conversion, leaving unreacted 4-acpy, which probably drove the arrangement of 1. Similarly to the analogous reactions with aryl methyl ketones, the best results were garnered using ACN under an O 2 pressure of 2.1 bars at 120 • C for 18 h, from which ina was isolated. This improved the conversion promoted by the formation of [Cu(ina) 2 (H 2 O] n that rapidly precipitated. Therefore, the remarkable difference in the conversion after changing the Cu(II) precursor demonstrates the significant effect of the counterion. Furthermore, the assays in DMF did not bring any evidence of 4-fopy nor ina ligand formation regardless of the employed Cu(II) salt. Therefore, it seemed that the catalytic performance of Cu(II) in α-oxygenation as well as in the C-C bond cleavage of heteroaromatic methyl ketones behaves similarly to their aryl analogues. Then, the formation of mixtures with 4-fopy when modifying the synthetic conditions is also provided probably as a result of incomplete conversion. It, therefore, appears that this progressive formation of ina, combined with the excess of 4-acpy, enabled its gradual nucleation and growth, granting the formation of suitable crystals for the X-ray diffraction of compound 1.
Supplementary Materials: The following supporting information can be downloaded at https: //www.mdpi.com/article/10.3390/ma16103724/s1. Figure S1: FTIR-ATR spectrum of compound 1. Funding: J.P. acknowledges financial support from the CB615921 project, the CB616406 project from "Fundació La Caixa", and the 2021SGR00262 project from the Generalitat de Catalunya. F.S.-F. acknowledges the PIF predoctoral fellowship from the Universitat Autònoma de Barcelona.