2.1. Synthesis
The Schiff base
3 was synthesized in one step by mixing equimolar quantities of
ortho-vanillin
1 and
gamma-aminobutyric acid
2 in the minimum amount of refluxing MeOH (
Scheme 1). After filtration and washing, product
3 was obtained in very good yield (76%). In order to further improve the yield of the reaction, the application of (a) glacial acetic acid as a mild acidic agent appropriate for such couplings [
15,
16], (b) sulfuric acid as a dehydrating acid [
17], and (c) piperidine as one the most commonly used bases for Schiff base formation of vanillin derivatives [
18] was explored (
Table 1). Piperidine seemed to partially “quench” the coupling, leading to lower yields, even after forcing the product precipitation. The presence of glacial acetic acid increased the yield of the reaction to almost quantitative (86%), whereas using concentrated sulfuric acid was proved to be unsuccessful.
The structure and purity of compound
3 was confirmed by
1H and
13C-NMR (
Supplementary Information, Figures S1–S6). As expected, the methylene protons of the amino acid unit appeared in the aliphatic region of the
1H-NMR spectrum. H-4 protons (see Figure 1A numbering) were shifted downfield at 3.60 ppm because of the nitrogen atom. The aromatic protons appeared according to the standard shift and splitting pattern of 1,2,3-trisubstituted benzene rings at 6.79, 7.00, and 7.02 ppm. The
13C-NMR spectrum is in good agreement with the structure and reported data [
19,
20]. The low-field signals of azomethine, C-7 and carboxylic carbons were assigned by 2D-NMR experiments (
Supplementary Information, Figures S3–S6) at 166.2, 151.9, and 174.0 ppm, respectively.
NOESY experiment demonstrated that 3 has the same configuration with the coordinated ligand, since a signal corresponding to azomethine proton (8.53 ppm) and H-9 of the ring (7.02 ppm) proximity was detected, thus proving the expected E-configuration.
Under standard NMR experiment conditions (0.05 M in DMSO-
d6) we were not able to distinguish the phenolic OH proton from the carboxylic OH proton, due to broadening of these peaks, leading to the absence of 2D signals. Even by modifying the conditions (concentration, temperature, and/or solvent) we did not observe the desired peak sharpening or appearance of any additional clarifying 2D signals. Since the structural elucidation by NMR of similar Schiff bases systems incorporating an
ortho-hydroxy phenyl unit have been reported in the literature [
19,
20], the broad peak at 12.2 ppm was assigned to the carboxylic proton, whereas the lower-field broad peak at 13.7 ppm was assigned to the deshielded phenolic proton.
For the synthesis of the heteroleptic Cu(II)-Schiff base complex (
4) (
Scheme 2) a thorough exploration of the experimental conditions regarding solvent system, pH, temperature, metal:ligand stoichiometry, and crystallization process was performed. Subsequently, complex
4 was synthesized from the reaction of Cu(NO
3)
2·3H
2O with the Schiff base in MeOH at 60 °C under reflux conditions, in the presence of sodium hydroxide (NaOH). The overall stoichiometric reaction leading to complex
4 is shown schematically below:
The reaction mixture was left to evaporate slowly at room temperature. Dark green crystalline material emerged in the reaction described above, the analytical composition of which was consistent with the formulation in complex 4. Positive identification of the crystalline product was achieved by elemental analysis, FT-IR, HR-ESI-MS, and X-ray crystallographic analysis of isolated single crystals from complex 4.
Both compounds are stable in air for fairly long periods of time. They readily dissolve in H2O, methanol (MeOH), dimethylacetamide (DMA), dimethyl sulfoxide (DMSO), and dimethylformamide (DMF) and are insoluble in acetone, acetonitrile, and dichloromethane at room temperature.
2.2. Description of X-ray Crystallographic Structure
The X-ray crystal structure of
4 reveals a discrete solid-state lattice. The molecular structure of
2 is given in
Figure 1A; selected bond distances and angles are listed in
Table 2. Complex
4 crystallizes in the monoclinic space group
C2/
c. The crystal structure reflects an one-dimensional polymeric compound forming infinite chains along the
c crystallographic axis. The unit cell contains four mononuclear [Cu(C
12H
14NO
4)
2] monomeric complex units and half of a badly disordered lattice MeOH molecule. The molecular structure of the monomer
4 consists of a Cu(II) ion bound to two singly deprotonated Schiff base bridging ligands which coordinate through their deprotonated phenolato oxygen atom, the imino nitrogen atom, and the double bonded oxygen atoms of the protonated carboxylic acid moieties from two neighboring molecules, thereby giving rise to a Cu
IIN
2O
4 chelation environment, and a coordination sphere reflecting a disordered octahedral geometry (
Figure 1A). The Cu-N bond lengths are 2.005(2) Å whereas the Cu-O bond lengths are in the range between 1.9272(16) and 2.6167(19) Å. These values are very similar to the related bond distances reported in the literature [
21]. Intermolecular hydrogen-bonding interactions arise between the deprotonated phenolic oxygen atoms and the protonated oxygen atoms of the carboxylic groups from the neighboring monomeric complex units enforcing the polymeric chains formation and resulting in the final 1D crystal lattice (
Figure 1B,
Supplementary Information Table S1).
2.3. FT-IR Spectroscopy
The FT-IR spectrum of the Schiff base
3 (
Supplementary Information, Figure S7) shows a weak band at 3419 cm
−1, characteristic of the
ν(OH) vibrations [
22], which disappears in the spectrum of complex
4 (
Supplementary Information, Figure S7), indicating deprotonation of the OH group upon binding with the Cu(II) ion. The
ν(C=N) vibrations are observed at 1643 cm
−1 for Schiff base
3 and at 1598 cm
−1 for complex
4, respectively. This lowering of resonance frequency by 45 cm
−1 for the C=N vibration clearly reveals the coordination of the Cu(II) ion with the imine nitrogen. Moreover, both spectra show broad absorption bands at about 3068–2758 cm
−1 and 3089–2818 cm
−1, respectively, which are assigned to the
ν(C–H) stretching vibrations of the aromatic moieties. The absorption bands located at 526 cm
−1 and 465 cm
−1 in the spectrum of complex
4 can be assigned to the
ν(Cu-O) and
ν(Cu-N) vibrations, respectively.
2.4. UV-Vis Spectroscopy
The UV–Vis spectra of the Schiff base
3 and complex
4 were recorded in MeOH at a concentration of 10
−5 M (
Figure 2). The electronic absorption spectrum of the Schiff base shows an absorption band at 293 nm and 417 nm that can be assigned to the
π→
π* transitions in the aromatic ring and
n→
π* transitions of the imine moiety, respectively. In the spectrum of
4, both absorption bands present significant hypsochromic and hyperchromic shifts compared to the free Schiff base, which can be attributed to the increased conjugation of the Cu(II)-Schiff base system. More specifically, the absorption band, indicative of the
π→
π* transitions, appears at 274 nm whereas the absorption band that arises from the
n→
π* transitions is located at 381 nm. No
d→d transitions were observed in the spectrum of
4, potentially because of the low concentration (10
−5 M) of the solution. However, additional measurements at a higher concentration (10
−3 M) (inset graph in
Figure 2) showed a broad absorption band at 682 nm, indicative of
d→d transitions.