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. 2020 Apr 20;5(17):10200–10206. doi: 10.1021/acsomega.0c01089

Complexes of N- and O-Donor Ligands as Potential Urease Inhibitors

Syed Raza Shah †,‡, Zarbad Shah ‡, Mohammed Khiat †, Ajmal Khan †, Leila R Hill §, Shakeel Khan ‡, Javid Hussain ∥, René Csuk ⊥, Muhammad U Anwar †,*, Ahmed Al-Harrasi †,*
PMCID: PMC7203987  PMID: 32391508

Abstract

graphic file with name ao0c01089_0008.jpg

We report five new transition-metal complexes that inhibit the urease enzyme. Barbituric acid (BTA), thiobarbituric acid (TBA), isoniazid (INZ), and nicotinamide (NCA) ligands were employed in complexation reactions. The resulting complexes were characterized using a variety of analytical techniques including infra-red and UV–vis spectroscopy, 1H NMR spectroscopy, elemental analysis, and single-crystal X-ray diffraction analysis. We describe two mononuclear complexes with a general formula {[M(NCA)2(H2O)4](BTA)2(H2O)}, where M = Co (1) and Zn (2), a mononuclear complex {[Ni(NCA)2(H2O)4](TBA)2(H2O)} (3), and two polymeric chains of a general formula {[M(INZ) (H2O)3](BTA)2(H2O)3}, where M = Co (4) and Zn (5). These complexes displayed significant urease enzyme inhibition with IC50 values in the range of 3.9–19.9 μM.

Introduction

Coordination complexes are mainly prepared using two approaches (i) the molecular self-assembly approach in which polydentate ligands with well-defined molecular binding sites are reacted with metals with preferred coordination geometries1 and (ii) the serendipitous approach, in which a range of ligands are combined with metal ions under carefully controlled conditions (solvent, temperature, pH etc.) and the metals often exhibit flexibility in their coordination geometries.2 The latter approach is extremely productive and has produced polymetallic clusters and cages with interesting properties.2 In addition, more than one organic ligand with known properties can be easily assembled in a single metal complex via a one-pot complexation reaction.3−10 For instance, two trans-[PtCl2(thiazole) (imidazole)]-mixed ligand complexes were reported by Al-Shuneigat et al., which exhibited greater activity than cisplatin against resistant cell lines.11 Moreover, a series of platinum complexes with terpyridine and glycosylated mixed ligands were prepared and were reported to exhibit not only enhanced solubility but also 100 times higher potency than cisplatin.12

Barbituric acid (BTA) and thiobarbituric acid (TBA) belong to the pyrimidine family, and exist in enol (4,6-dioxo-2-thio-pyrimidine) and keto (4,6-dihydroxy-2-mercaptopyrimidine) forms.13,14BTA derivatives–barbiturates—are used as sedatives, anticonvulsants, and anesthetics as they induce a depressant effect on the central nervous system.13,15TBA is famous for the so-called “TBA test” for the measurement of lipid oxidation and for the measurement of the oxidative state of biological and food materials.16 Both compounds have been extensively studied for their antimicrobial, anti-inflammatory, and antitumor properties.17−19 Isoniazid (INZ) and nicotinamide (NCA) belong to the pyridine family, and are both N- and O- donor ligands (Figure 1). The coordination chemistry of INZ and NCA is well-developed and their resulting complexes have been extensively studied as antibacterial and antifungal agents,20,21 as well as in crystal engineering for the synthesis of supramolecular frameworks of coordination compounds.22 Complexes of INZ or NCA containing BTA or TBA are unknown. We were interested to combine the established antibacterial properties of these ligands and to prepare structurally well-defined transition metal complexes of INZ and NCA with BTA and TBA, using a serendipitous self-assembly approach. We were particularly interested in the urease inhibition of the selected transition metal complexes of the above-mixed ligand systems. Urease, a binuclear Ni(II)-containing enzyme, is responsible for catalyzing the decomposition of urea into ammonia and carbon dioxide, and is commonly found in plants,23 bacteria,24 and soil.25 The rapid decomposition of urea has an adverse effect on humans, animals, and plantlife.26 For example, in humans this decomposition process has been linked to a plethora of ailments, including, peptic ulcers, stomach cancer, gastric infections (e.g. by Helicobacter pylori), dental plaque, kidney stone formation, and pyelonephritis.27 Urease is an immunogenic protein and is responsible for producing antibodies in human sera that are connected with the progress of diseases such as rheumatoid arthritis, atherosclerosis, or urinary tract infections.28 Urease inhibitors, including synthetic organic compounds, plant extracts, and metal salts, reduce the activity of the urease enzyme. However, most of these inhibitors are associated with toxicity and/or side effects,29−34 and so alternative strategies including those involving the use of the first row and inner transition metal complexes have been extensively investigated.35

Figure 1.

Figure 1

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Structural representations of the ligands.

In this study, we have investigated the reactions of BTA, TBA, INZ, and NCA (Figure 1) with selected d-block metals, and described two mononuclear complexes with a general formula {[M(NCA)2(H2O)4](BTA)2(H2O)} where M = Co (1) and Zn (2), a mononuclear complex {[Ni(NCA)2(H2O)4](TBA)2(H2O)} (3), and two polymeric chains with a general formula {[M(INZ) (H2O)3](BTA)2(H2O)3} where M = Co (4) and Zn (5), shown in Figure 2. The structures of 1–5 were analyzed by single-crystal X-ray diffraction. The bulk composition was confirmed by 1H NMR, elemental analysis, UV–vis, and infra-red spectroscopy. In vitro urease enzyme inhibition studies were performed.

Figure 2.

Figure 2

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Synthetic routes to {[M(NCA)2(H2O)4](BTA)2(H2O)} where M = Co (1) and Zn (2), {[Ni(NCA)2(H2O)4](TBA)2(H2O)} (3), and {[M(INZ)2(H2O)3](BTA)2(H2O)3}n where M = Co (4) and Zn (5).

Result and Discussion

Synthesis

Reactions of NCA, BTA, and TBA with M(CH3COO)2 (where M = Co, Zn, and Ni) in methanol produced mononuclear complexes of Co (1), Zn (2), and Ni (3). When NCA was replaced with INZ, two polymeric chains of Co (4) and Zn (5) were isolated (Figure 2). All five complexes were characterized by single-crystal X-ray diffraction, elemental analysis, 1H NMR, UV–vis, and IR spectroscopy. Single crystals were grown directly from the mother liquor.

Analytical Data and Spectral Characterization

Complexes 1–5 were obtained in good yield (61–86%) in an analytically pure form, and were soluble in water, methanol, and dimethyl sulfoxide (DMSO). The IR spectra of complexes 1–5 are presented in Figure S1 of the Supporting Information. The broad absorption bands in the range 2920–3619 cm–1 are attributed to the O–H stretching frequency, which are broadened because of hydrogen bonding, while the absorption bands in the range 1590–1650 cm–1 were attributed to the carbonyl group. The peaks in the range 1512–1515 cm–1 reflect the presence of the heterocyclic C–N stretching.36

The UV–vis data for complexes 1–5 in noncoordinating solvents were hindered by insolubility. Therefore, the UV–vis spectral data for complexes were measured in water. The spectra are dominated by an intense π–π* ligand-centered absorption band between 200 and 300 nm compared to the free ligands (Figure S2). The increase in the absorption coefficient (ε) of complexes 1–5 compared to the free ligands supports the suggestion that these ligands remain coordinated in solution, with metal coordination enhancing the extinction coefficient. The 1H NMR spectra of diamagnetic complexes 2 and 5 were recorded in DMSO-d6. On comparing the peaks of free ligands37,38 with those of complexes 2 and 5, it was observed that all the signals of the free ligands are present in the 1H NMR spectra of the complexes. The signals at 4.08 ppm (in the case of complex 2) and 4.19 ppm (in the case of complex 5) were assigned to C–H protons in the BTA– anion. The N–H protons for BTA– were observed as broad singlets at 9.39 and 9.64 ppm for complexes 2 and 5, respectively (Figures S3 and S4). The NMR signals shifted downfield when compared to the free ligands, indicating the presence of complexation products in solution.

Crystal Structure Description

{[Co(NCA)2(H2O)4][BTA]2(H2O)2} (1) and {[Zn(NCA)2(H2O)4][BTA]2(H2O)2} (2)

Complexes 1 and 2 are mononuclear compounds of general formula {[M(NCA)2(H2O)4][BTA]2(H2O)2}. The molecular structures of 1 and 2 are shown in Figures 3 and S5 respectively, while the selected interatomic distances and angles for 1 are listed in Table 2. Complexes 1 and 2 were found to be isostructural, so only complex 1 is discussed in detail here as a representative species. Complex 1 crystallizes in the triclinic space group P1̅, with one NCA ligand, half a Co2+ ion, two coordinated water molecules, and a deprotonated BTA– anionic ligand in the asymmetric unit. The coordinated NCA ligand is neutral and the Co2+ cation is charge balanced by two uncoordinated BTA– anions, which satisfy the overall charge on complex 1. The Co2+ ion adopts a slightly distorted six-coordinate octahedral geometry comprising an [N2O4] donor set. The Co2+ ion is located at the center of symmetry and is coordinated by two nitrogen atoms (N2 and N2i) of two pyridine rings of the NCA ligands and four oxygen atoms [O1, O1i, O2, and O2i] from four water ligands [(i) −x + 2, −y + 1, −z + 1]. The Co–N distance is 2.1746(14) Å while Co–Owater distances are 2.0456(12) Å and 2.1152(13) Å. The oxygen atom (O4) of the uncoordinated BTA– anion forms hydrogen bonds with water molecules coordinated to the Co2+ cation resulting in a hydrogen-bonded supramolecular chain in the a-direction (Figure 4). The structure is additionally stabilized via intermolecular π···π stacking between the NCA and BTA– ligands, with centroid–centroid (Cg···Cg) distances of 3.579 and 3.858 Å (Figure S6).

Figure 3.

Figure 3

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Molecular structure of {[Co(NCA)2(H2O)4][BTA]2(H2O)2} (1), thermal ellipsoids are shown at the 50% probability.

Table 2. Selected Interatomic Distances (Å) and Angles (deg) for 1a.
Co1–O2i 2.0456(12) Co1–O3i 2.1152(13)
Co1–O2 2.0456(12) Co1–N2 2.1746(14)
Co1–O3 2.1152(13) Co1–N2i 2.1746(14)
O2i–Co1–O2 180.0 O2–Co1–N2 91.94(5)
O2i–Co1–O3 89.77(5) O3–Co1–N2 88.21(5)
O2–Co1–O3 90.23(5) O3i–Co1–N2 91.79(5)
O2i–Co1–O3i 90.23(5) O2i–Co1–N2i 91.94(5)
O2–Co1–O3i 89.77(5) O2–Co1–N2i 88.06(5)
O3–Co1–O3i 180.00(6) O3–Co1–N2i 91.79(5)
O2i–Co1–N2 88.06(5) O3i–Co1–N2i 88.21(5)
N2–Co1–N2i 180.0    
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a

Symmetry code: (i) −x + 2, −y + 1, −z + 1.

Figure 4.

Figure 4

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Hydrogen bonds (shown in blue) in {[Co(NCA)2(H2O)4](BTA)2(H2O)} (1), parallel to the a-axis.

{[Ni(NCA)2(H2O)4][TBA]2(H2O)2} (3)

The molecular structure of 3 is shown in Figure 5, and selected interatomic distances and angles are listed in Table 3. Complex 3 crystallizes in the monoclinic space group P21/c, with half of the molecule in the asymmetric unit. In complex 3, the Ni2+ cation is charge balanced by two uncoordinated TBA– anions, which satisfy the overall charge on the complex 3. The Ni2+ ion adopts a slightly distorted six-coordinate octahedral geometry comprising an [N2O4] donor set. The Ni2+ ion is located at the center of symmetry and is coordinated by two nitrogen atoms (N2 and N2i) of two pyridine rings of the NCA ligands and four oxygen atoms [O1, O1i, O2, and O2i] from four water ligands [(i) −x + 2, −y + 1, −z + 1]. The Ni–N distance is 2.120(4) Å, while Ni–Owater distances are 2.076(3) and 2.083(3) Å. The Owater atoms (O1, O2) coordinated to Ni2+ form hydrogen bonds with OTBA (O4, O5) and lattice water molecules (O6). The hydrogen bonding between TBA, the water molecules, and NCA gives the 3-D arrangement of 3 as depicted in Figure 6. The structure is additionally stabilized by intermolecular π···π stacking between NCA and BTA– ligands, with centroid–centroid (Cg···Cg) distances of 3.579 and 3.858 Å (Figure S7).

Figure 5.

Figure 5

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Molecular structure of {[Ni(NCA)2(H2O)4][TBA]2(H2O)2} (3): H-bonds are shown in blue.

Table 3. Selected Interatomic Distances (Å) and Angles (deg) for 3a.
Ni1–O1 2.076(3) Ni1–O2 2.083(3)
Ni1–O1i 2.076(3) Ni1–N1 2.120(4)
Ni1–O2i 2.083(3) Ni1–N1i 2.120(4)
O1–Ni1–O1i 180.0 O2i–Ni1–N1 91.11(14)
O1–Ni1–O2i 92.30(13) O2–Ni1–N1 88.89(14)
O1i–Ni1–O2i 87.70(13) O1–Ni1–N1i 88.64(13)
O1–Ni1–O2 87.70(13) O1i–Ni1–N1i 91.36(13)
O1i–Ni1–O2 92.30(13) O2i–Ni1–N1i 88.89(14)
O2i–Ni1–O2 180.0 O2–Ni1–N1i 91.11(14)
O1–Ni1–N1 91.36(13) N1–Ni1–N1i 180.00(18)
O1i–Ni1–N1 88.64(13)    
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a

Symmetry code: (i) −x + 1, −y + 1, −z + 1.

Figure 6.

Figure 6

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H-bonded packing of 3.

{[Co(INZ)(H2O)3](BTA)2(H2O)3}n (4) and {[Zn(INZ)(H2O)3][BTA]2(H2O)3}n (5)

Complexes 4 and 5 are one-dimensional coordination polymers of general formula {[M(INZ)(H2O)3][BTA]2(H2O)3}n. The molecular structures of 4 and 5 were found to be isostructural, and so only complex 4 is discussed here as a representative species. The structures of 4 and 5 are shown in Figures 7 and S8, respectively, while selected interatomic distances and angles of 4 are listed in Table 4. This complex crystallizes in the monoclinic space group P21/n, with one INZ ligand, one Co2+ ion, three coordinated water molecules, two deprotonated BTA– anions, and three lattice water molecules in the asymmetric unit. In complex 4, the INZ ligand is neutral, and the Co2+ cation is charge balanced by two uncoordinated BTA– anions, which satisfy the overall charge on the complex. The Co2+ ion adopts a slightly distorted six-coordinate octahedral geometry comprising an [N2O4] donor set. The Co–Npy (N3) and Co–Nhydrazone (N1) distances are 2.134(2) and 2.155(3) Å while the Co–Ohydrazone (O1) distance is 2.106(2) Å. The Co–Owater (O3, O4, and O5) distances are in the range 2.074(2)–2.111(3) Å. The structure is stabilized by a variety of very complex hydrogen bondings. The water molecules coordinated to Co2+ form hydrogen bonds with BTA— anions (O4–H4A···O13 and O3–H3B···O12). The lattice water molecules form hydrogen bonds with one another (O23–H23B···O24, O22–H22A···O24) and with BTA— anions (N8–H8···O23, O24–H24A···O12, and O22–H22···O11) as well as with Nhydrazone (N2–H2···O22, Figure S9). The structure is additionally stabilized by intermolecular π···π stacking between NCA and BTA– ligands, with centroid–centroid (Cg···Cg) distances of 3.533 and 4.162 Å (Figure S10).

Figure 7.

Figure 7

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Structure of the [Co(INZ)(H2O)3]n unit in 4 viewed along the a-axis. The lattice BTA– and water molecules are removed for clarity.

Table 4. Selected Interatomic Distances (Å) and Angles (deg) for 4a.
Co1–O4 2.074(3) Co1–O5 2.110(2)
Co1–O3 2.077(3) Co1–N3i 2.134(3)
Co1–O1 2.107(2) Co1–N1 2.156(3)
O4–Co1–O3 175.03(10) O1–Co1–N3i 177.91(9)
O4–Co1–O1 89.29(9) O5–Co1–N3i 90.83(10)
O3–Co1–O1 86.41(9) O4–Co1–N1 88.10(12)
O4–Co1–O5 87.76(11) O3–Co1–N1 93.43(10)
O3–Co1–O5 89.75 (9) O1–Co1–N1 77.80(10)
O1–Co1–O5 90.21(10) O5–Co1–N1 167.36(10)
O4–Co1–N3i 92.56(9) N3i–Co1–N1 101.29(10)
O3–Co1–N3i 91.79(9)    
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a

Symmetry codes: (i) x – 1/2, −y + 3/2, z – 1/2; (ii) x + 1/2, −y + 3/2, z + 1/2.

Urease Enzyme Inhibition

The urease inhibitory activity of complexes 1–5 was investigated. All five complexes showed significant urease inhibition with IC50 values ranging from 3.9 ± 0.238 to 19.9 ± 0.280 μM, when compared with thiourea standard (IC50 = 20.8 ± 0.75 μM) (Table 5). The preliminary structure–activity relationship showed that the excellent activities of these compounds may be attributed to the different metals in the complexes. Complex 3 was the most active compound in the series (IC50 = 3.9 ± 0.238 μM) and exhibited greater activity to the thiourea standard. The dose-dependent inhibition of complex 3 at various concentrations is presented in Figure S11. This superior activity could be due the presence of the TBA anion, which is absent in other complexes.38−40

Table 5. Urease Inhibition of Complexes 1–5.

complexes IC50 ± SEM (μM)
1 7.5 ± 0.090
2 18.1 ± 1.828
3 3.9 ± 0.238
4 19.9 ± 0.280
5 5.3 ± 0.240
standard (thiourea) 20.8 ± 0.75
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Conclusion

The synthesis, structure, and urease inhibition studies of five novel first row transition metal complexes containing BTA-, TBA-, INZ-, and NCA-mixed ligands were described. Our investigations have given rise to a variety of structural variations. Complexes 1–3 are mononuclear while complexes 4 and 5 are 1-D polymeric chains. The complexes showed significant urease inhibition with IC50 values ranging from 3.9 ± 0.238 to 19.9 ± 0.280 μM. These complexes clearly show their potential to inhibit the urease enzyme and are likely candidates for the development of new drug formulations, but more detailed in vivo studies are required to understand their mechanism of action. Future reactions of the above-mixed ligand systems with other 3d- and 4f-metal ions are currently under investigation.

Experimental Section

General Considerations

Solvents, ligands, and metal salts were obtained from commercial suppliers and used without further purification.

Physical Measurements

Melting points were determined using a Stanford Research Systems MPA120 EZ-Melt automated melting point apparatus. Elemental compositions were determined with a PerkinElmer 2400 Series II CHNS/O Analyzer. The UV–vis spectra were measured using an Agilent 8453 spectrophotometer using 10–5 to 10–6 M solutions in water in the range 200–400 nm. The IR spectra were obtained using a Bruker ALPHA FT-IR spectrometer equipped with a platinum single reflection diamond ATR module. The 1H NMR spectra were recorded on a Bruker 600 MHz spectrometer in DMSO-d6.

Assay for Urease Inhibition

In a 200 μL reaction mixture, 25 μL of urease enzyme from Canavalia ensiformis (jack bean), 5 μL of samples with different concentrations, and 55 μL of urea (100 mM) were incubated for 15 min at 30 °C in 96-well plates. Subsequently, a 45 μL phenol/sodium nitroprusside mixture (1% w/v; 0.005% w/v) and 70 μL of NaOH/NaOCl alkali mixture (0.5% w/v; 0.1% w/v) were added and the urease activity was measured using the indophenol method as described by Weatherburn.41 All reactions were performed in phosphate buffer at 6.8 pH and changes in absorbance were measured at 630 nm with a microplate reader (xMark Microplate Spectrophotometer, BIO-RAD) for 50 min. Assays were replicated thrice and thiourea was used as the positive control.42 The results were processed using Microsoft Excel and the EZ-Fit Enzyme Kinetics program. The percent inhibition was calculated with the formula given below

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Statistical Analysis

The IC50 values for each compound were calculated using the EZ-Fit Enzyme Kinetics program (Perrella Scientific Inc., Amherst, USA).

X-ray Crystallography

The crystal data are summarized in Table 1. Single crystals of 1–5 were mounted on a MiTeGen loop with grease and examined on a Bruker D8 VENTURE APEX diffractometer equipped with a Photon 100 CCD area detector at 296 (2) K using graphite-monochromated Mo Kα radiation (λ = 0.71073 Å). Data were collected using APEX-II software,43 integrated using SAINT,44 and corrected for absorption using a multiscan approach (SADABS).45 Final cell constants were determined from a full least-squares refinement of all the observed reflections. The structure was solved using intrinsic phasing (SHELXT).46 All non-H atoms were located in subsequent difference maps and refined anisotropically with SHELXL-2014/7.47 H-atoms were added at the calculated positions and refined with a riding model. H atoms on O atoms were located in the difference map and refined isotropically with U(iso) riding on the O with DFIX constraints applied. The structures of 1–5 have been deposited with the CCDC (CCDC deposition numbers 1981754–1981758).

Table 1. Crystallographic Data for Complexes 1–5.

  1 2 3 4 5
chemical formula C14H25CoN7O13 C14H24.64N7O13Zn C20H30N8NiO12S2 C20H30CoN8O14 C14H24.64N7O13Zn
Mr 665.45 671.89 697.35 558.34 564.42
crystal system, space group triclinic, P1̅ triclinic, P1̅ monoclinic, P21/c monoclinic, P21/n monoclinic, P21/n
temperature (K) 296 296 296 296 296
a, b, c (Å) 7.1297(6), 7.9881(8), 12.2187(8) 7.152(3), 7.947(4), 12.222(5) 7.1817(9), 8.3024(10), 23.248(3) 11.564(5), 11.051(5), 18.100(7) 11.5555(6), 11.0401(6), 18.0417(8)
α, β, γ (deg) 84.616(2), 86.409(4), 82.067(4) 84.70(2), 86.949(13), 82.23(2) 91.594(5) 107.954(14) 107.654(2)
V (Å3) 685.32(10) 684.7(6) 1385.6(3) 2200.4(16) 2193.25(19)
Z 1 1 2 4 4
μ (mm–1) 0.71 0.98 0.93 0.86 1.20
Tmin, Tmax 0.687, 0.745 0.671, 0.745 0.649, 0.745 0.672, 0.745 0.565, 0.745
[I > 2σ(I)] 19 633, 2812, 2522 17 923, 2809, 2456 3630, 3630, 3445 28 254, 4501, 3700 67 201, 4533, 3834
Rint 0.042 0.050 0.0368 0.033 0.058
(sin θ/λ)max (Å–1) 0.627 0.627 0.628 0.627 0.628
R[F2> 2σ(F2)], wR(F2), S 0.029, 0.091, 1.23 0.030, 0.076, 1.08 0.036, 0.145, 1.34 0.051, 0.159, 1.04 0.035, 0.132, 1.09
no. of reflections 2812 2809 3630 4501 4533
no. of parameter 220 223 215 341 386
no. of restraints 8 8 6 6 13
Δρmax, Δρmin (e Å–3) 0.37, −0.54 0.22, −0.38 0.47, −0.52 0.90, −0.75 0.32, −0.55
CCDC 1 981 754 1 981 755 1 981 756 1 981 757 1 981 758
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Synthesis of the Complexes

Preparation of {[Co(NCA)2(H2O)4][BTA]2(H2O)2} (1)

BTA (0.128 g, 1.0 mmol) and Co(CH3COO)2·4H2O (0.249 g, 1.0 mmol) were heated under reflux in water (30 mL) for 30 min. NCA (0.122 g, 1.0 mmol) in water (10 mL) was added to the reaction mixture and the resulting solution was heated under reflux for 20 min. The solution was then filtered and left undisturbed at room temperature. Dark pink crystals were formed after two weeks. Yield: 0.380 g, 74%; mp above 300 °C; UV–vis (7.6 × 10–6 M, H2O): 213 (20 357, 257 (37 479), λmax, nm; ε, M–1 cm–1); selected IR data (cm–1): ν 3610–2900 (OH), ν 1718 (C=O BTA), ν 1680 (C=O NCA), ν 1587 (C=N aromatic). Elemental analysis calcd (%) for C20H30CoN8O14·H2O: C, 35.15; H, 4.72; N, 16.40. Found: C, 35.18; H, 4.26; N, 16.28.

Preparation of {[Zn(NCA)2(H2O)4][BTA]2(H2O)2} (2)

BTA (0.128 g, 1.0 mmol) and Zn(CH3COO)2·2H2O (0.0.219 g, 1.0 mmol) were heated under reflux in water (30 mL) for 30 min. NCA (0.122 g, 1.0 mmol) in methanol (5 mL) was added to the reaction mixture and the resulting solution was heated under reflux for 1 h. The solution was then filtered and left undisturbed at room temperature. Colorless crystals suitable for X-ray diffraction were collected after one week. Yield: 0.510 g, 79%; mp 205–210 °C; UV–vis (7.3 × 10–6 M), H2O, 213 (24 397), 257 (45 173); selected IR data (cm–1): ν 3508–2750 (OH), ν 1719 (C=O BTA), ν 1660 (C=O NCA), and ν 1560 (C=N). 1H NMR (600 MHz, DMSO-d6): δ 9.39 (s, 2H), 9.00 (d, J = 2.2 Hz), 8.68 (d, J = 4.8 Hz, 1H), 8.19 (d, J = 7.9 Hz, 1H), 8.15 (s, 1H), 7.58 (s, 1H), 7.49 (dd, J = 7.9, 4.9 Hz, 1H), 4.07 (s, 1H). Elemental analysis calcd (%) for C20H30N8O14Zn: C, 35.75; H, 4.50; N, 16.68. Found: C, 35.29; H, 4.11; N, 16.12.

Preparation of {[Ni(NCA)2(H2O)4][TBA]2(H2O)2} (3)

TBA (0.144 g, 1.0 mmol) and Ni(CH3COO)2·4H2O (0.248 g, 1.0 mmol) were heated under reflux in water (30 mL) for 30 min. NCA (0.122 g, 1.0 mmol) in water (10 mL) was added to the reaction mixture and the resulting solution was heated under reflux for 30 min. The solution was then filtered and left undisturbed at room temperature. Light blue crystals were formed after two weeks. Yield: 0.403 g, 61%; mp above 300 °C; UV–vis (9.6 × 10–6 M), H2O, 242 (20 044), 263 (36 574); selected IR data (cm–1): ν 3450–3124 (OH), ν 1671 (C=O TBA), ν 1590 (C=N aromatic). Elemental analysis calcd (%) for C20H30N8NiO12S2·(H2O): C, 33.58; H, 4.51; N, 15.66. Found: C, 33.74; H, 4.13; N, 15.48.

Preparation of {[Co(INZ)2(H2O)3]n(BTA)2(H2O)3}n (4)

BTA (0.128 g, 1.0 mmol) and Co(CH3COO)2·4H2O (0.249 g, 1.0 mmol) were heated under reflux in water (30 mL) for 30 min. INZ (0.137 g, 1.0 mmol) in water (15 mL) was added to the reaction mixture and the resulting solution was stirred at room temperature for 20 min. The solution was then filtered and left undisturbed at room temperature. Light pink crystals were formed after two days. Yield: 0.526 g, 80%; mp above 300 °C; UV–vis (1.4 × 10–5 M), H2O, 257 (44 569); selected IR data (cm–1): ν 3608–2902 (OH), ν 1673 (C=O BTA), ν 1585 (C=N aromatic). Elemental analysis calcd (%) for C10H17CoN5O8: C, 30.45; H, 4.35; N, 17.77. Found: C, 31.21; H, 4.15; N, 17.71.

Preparation of {[Zn(INZ)2(H2O)3]n(BTA)2(H2O)3}n (5)

BTA (0.128 g, 1.0 mmol) and Zn(CH3COO)2·2H2O (0.219 g, 1.0 mmol) were combined and stirred and heated under reflux in water (30 mL) for 30 min. INZ (0.137 g, 1.0 mmol) in water (15 mL) was added to the reaction mixture and the resulting solution was stirred and heated under reflux for 20 min. The solution was then filtered and left undisturbed at room temperature. Colorless crystals were formed after two days. Yield: 0.570 g, 86%; mp above 300 °C; UV–vis (7.3 × 10–6 M), H2O, 212 (12 800), 257 (50 309); selected IR data (cm–1): ν 3603–2900 (OH), ν 1668 (C=O BTA), and ν 1583 (C=N aromatic). 1H NMR (600 MHz, DMSO-d6): δ 9.65 (s, 2H), 8.71 (d, J = 5.0 Hz, 2H), 7.76 (d, J = 5.0 Hz, 2H), 5.20 (s, 2H), 4.19 (s, 1H). Elemental analysis calcd (%) for C10H17N5O8Zn: C, 29.96; H, 4.28; N, 17.48. Found: C, 30.08; H, 3.83; N, 17.43.

Acknowledgments

The authors would like to thank the University of Nizwa and The Oman Research Council (TRC) for their generous support.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.0c01089.

The authors declare no competing financial interest.

Supplementary Material

ao0c01089_si_001.pdf (643.8KB, pdf)
ao0c01089_si_002.cif (4.1MB, cif)

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ao0c01089_si_001.pdf (643.8KB, pdf)
ao0c01089_si_002.cif (4.1MB, cif)

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