Journal of Chemistry
Volume 2016 (2016), Article ID 7317015, 8 pages
http://dx.doi.org/10.1155/2016/7317015

Research Article

Synthesis, Characterization, and Antimicrobial Activities of Coordination Compounds of Aspartic Acid

T. O. Aiyelabola,1,2 D. A. Isabirye,² E. O. Akinkunmi,³ O. A. Ogunkunle,¹ and I. A. O. Ojo¹

¹Department of Chemistry, Obafemi Awolowo University, Ife Central, Ile-Ife 220282, Osun State, Nigeria
²Department of Chemistry NWU, Mafikeng Campus, Private Bag X2046, Mmabatho 2735, South Africa
³Department of Pharmaceutics, Obafemi Awolowo University, Ife Central, Ile-Ife 220282, Osun State, Nigeria

Received 1 September 2015; Accepted 27 October 2015

Academic Editor: Nigam P. Rath

Copyright © 2016 T. O. Aiyelabola et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract.

Coordination compounds of aspartic acid were synthesized in basic and acidic media, with metal ligand M : L stoichiometric ratio 1 : 2. The complexes were characterized using infrared, electronic and magnetic susceptibility measurements, and mass spectrometry. Antimicrobial activity of the compounds was determined against three Gram-positive and three Gram-negative bacteria and one fungus. The results obtained indicated that the availability of donor atoms used for coordination was a function of the pH of the solution in which the reaction was carried out. This resulted in varying geometrical structures for the complexes. The compounds exhibited a broad spectrum of activity and in some cases better activity than the standard.

1. Introduction

Much attention is being paid to coordination compounds as potential antimicrobial agents in recent times. This is due to the improved activity of drugs administered as complexes [1–6]. It has been suggested that ligands with nitrogen and oxygen donor systems might inhibit enzyme production. This is because the enzymes which require these groups for their activity appear to be especially more susceptible to deactivation by the metal ion upon chelation [2]. Such compounds include coordination compounds of amino acids, such as aspartic acid. Aspartic acid (Figure 1) is a naturally occurring amino acid and a component of the active centre of some enzymes. It possesses three potential donor sites (one amine group and two carboxyl ones) [7, 8]. Aspartic acid has been reported as bidentate, as tridentate, and as a bridging ligand [9–15]. Its coordination behaviour may therefore be studied by comparing the complexes it forms with a series of metal ions of the same valency at relevant pH ranges [12, 14, 15]. Various structural possibilities for the corresponding metal complexes are thus expected [16–20]. Coordination compounds of amino acids, such as histidine [21], arginine, glutamic acid [14, 16], and aspartic acid [13, 22], have been studied. These coordination compounds were reported to demonstrate activity varying from marginal to significantly good antimicrobial properties. However, little attention has been focused on coordination compounds of aspartic acid as a tridentate ligand. As a result of resistance to the drugs currently in use and the emergence of new diseases, there is a continuous need for the synthesis and identification of new compounds as potential antimicrobial agents. Therefore we considered it necessary to study the effects of the possible varying structures of coordination compounds of aspartic acid on their antimicrobial activity, as this would yield information useful for designing antimicrobial agents. We therefore report the syntheses of coordination compounds of aspartic acid in acidic and basic media and their characterization and antimicrobial activities.

Figure 1

2. Experimental

2.1. Materials and Methods

All reagents and solvents used were of analytical grade. The infrared spectra were recorded on a Genesis II FTIR spectrophotometer in the range 450–4200 cm⁻¹. The electronic absorption spectra of the complexes in the range 200–1000 nm were obtained with a Genesis 10 UV-Vis spectrophotometer, solid reflectance. Melting points or decomposition temperatures (m.p./d.t.) were measured using open capillary tubes on a Gallenkamp (variable heater) melting point apparatus. The in vitro antimicrobial properties of the complexes were determined using a modification of the literature procedure [23]. Magnetic susceptibility was obtained using a Gouy balance at room temperature. Mass spectrometry for one of the complexes was carried out using Fisons VG Quattro spectrophotometer.

2.2. Syntheses of Complexes

The complexes were prepared according to a modification of literature procedure [13, 24, 25]. The general equations for the reactions are as follows:

 ML₂ complexes: MCl₂ + 2H₂L → MHL₂ + 2HCl Na₂[ML₂] complexes: MCl₂ + 2H₂L + 2NaOH → Na₂[ML₂] + 2HCl + 2H₂O where M = Co(II), Cu(II), Mn(II), Ni(II), Cd(II); L = (+)-aspartic acid.

2.2.1. ML₂ Complexes

A solution of (+)-aspartic acid (0.02 M, 2.67 g) was added to 0.01 M of appropriate metal(II) chloride salt (1.62, 2.17, 2.43, 2.51, and 2.69 g) for copper, cadmium, nickel, cobalt, and manganese, respectively, and dissolved in 20 mL of distilled water, with stirring; pH range for the reactions was 2.01–2.21. The mixtures were heated with stirring for 2 h, using a water bath. The resultant solutions were further concentrated until a scum was formed and then cooled. Crystals obtained were filtered and washed with methanol and then dried in a vacuum oven at 60°C.

2.2.2. Na₂[ML₂] Complexes

Appropriate metal(II) chloride salt solutions (0.02 M; 3.31, 4.47, 4.88, 5.05, and 5.34 g) for copper, cadmium, nickel, cobalt, and manganese, respectively, were dissolved in minimal amount of distilled water with warming until a clear solution was obtained. (+)-Aspartic acid (0.04 M, 5.42 g) was dissolved in distilled water and warmed over a steam bath. 0.04 M NaOH was then added with stirring, such that the pH range of the reaction was about 8–10. The metal(II) solution was then added and the mixture was refluxed for 2 h. The product obtained was allowed to cool overnight with the formation of crystals. The crystals obtained were filtered, washed with methanol, and dried in an oven at 60°C.

2.3. Antimicrobial Activity Using Disc Diffusion Assay

The in vitro antimicrobial screening effects of the ligand and complexes were evaluated using the disc diffusion method as previously reported [26]. The strains used were Escherichia coli NCTC 8196, Pseudomonas aeruginosa ATCC 19429, Staphylococcus aureus NCTC 6571, Proteus vulgaris NCIB, Bacillus subtilis NCIB 3610, and one Methicillin resistant S. aureus clinical isolate for bacteria and C. albicans NCYC 6 for fungi. All the tests were performed in triplicate.

3. Results and Discussion

3.1. Physicochemical Analysis

All the complexes were insoluble in major organic solvents; however they were soluble in hot water. The melting points or decomposition temperatures for the complexes are shown in Table 1. Most of the complexes decomposed before melting.

Table 1: Some physicochemical properties of the compounds.

Compound
Empirical formulae
Colour
m.p./d.t. (°C)
Yield (%)

Co(d-asp)₂
Co(C₄H₈O₄N)
Lilac
217
74.20

Cu(d-asp)₂
Cu(C₄H₈O₄N)
Blue
205
57.21

Mn(d-asp)₂
Mn(C₄H₈O₄N)
White
304()
81.84

Ni(d-asp)₂
Ni(C₄H₈O₄N)
Green
197()
66.00

Cd(d-asp)₂
Cd(C₄H₈O₄N)
White
204()
62.40

Na₂[Co(d-asp)₂]
Na[Co(C₄H₈O₄N)]
Purple
>320
62.60

Na₂[Cu(d-asp)₂]
Na[Cu(C₄H₈O₄N)]
Blue
215()
84.20

Na₂[Mn(d-asp)₂]
Na[Mn(C₄H₈O₄N)]
White
301–303()
68.50

Na₂[Ni(d-asp)₂]
Na[Ni(C₄H₈O₄N)]
Green
294()
62.70

Na₂[Cd(d-asp)₂]
Na[Cd(C₄H₈O₄N)]
White
287()
69.60

(): decomposition temperature.

3.2. Infrared Spectra

The infrared spectrum of the free ligand exhibited a broad band at 3380 cm⁻¹ which was assigned to the NH₂ stretching frequency. Intense bands at 1650 and 1583 cm⁻¹ were observed and are attributed to and stretching frequencies, respectively [27, 28]. The asymmetric and symmetric stretching frequencies on coordination were shifted to higher and lower wave numbers, for Na₂[ML₂] complexes, indicating that the oxygen atom of the carboxylate group of the ligand was used for coordination, Figures 2 and 3 [12, 28]. For the ML₂ complexes the asymmetric stretching frequencies were shifted to higher frequencies compared with that of the ligand in the order Co > Mn > Ni with the exception of the copper complex in which an hypsochromic shift was observed. No shift was observed for the cadmium complex. It is suggested that this arrangement may be as a result of the size of the metal ions [28–30]. In some of the Na₂[ML₂] complexes (Table 2) two bands were observed on coordination for the asymmetric and symmetric stretching frequencies. These indicate the possible mode of coordination of aspartic acid to the central metal ion via both oxygen atoms of the α- and β-carboxylate ion. Consequently, in these complexes, aspartic acid may be said to be tridentate, an observation that is in agreement with that obtained by previous workers [10]. Hypsochromic shifts were observed for the –NH₂ frequencies on coordination, for the ML₂ and Na₂[ML₂] complexes. This indicates bond elongation on coordination. It therefore suggests probable square planar and distorted octahedral geometry for the complexes, respectively. New bands in the spectra of the complexes at 500–598 cm⁻¹ were assigned to (M–N) stretching frequency. The participation of the lone pairs of electrons on the N of the amino group in the ligand in coordination is supported by these band frequencies [31]. Bands in the region of 604–724 cm⁻¹ indicate the formation of M–O bond and further support the coordination of the ligand to the central metal ions via the oxygen atom of the carboxylate group [29].

Table 2: Electronic spectra bands, for the compounds.

Compound
Band I
Band II
Band III
-
Magnetic moment (BM)

Aspartic acid
196
212
8231

—

Cu(asp)₂
241
259
391
628, 667
2.47

Cd(asp)₂
238
259
271
—
0.00

Ni(asp)₂
232
265
—
517
3.28

Co(asp)₂
—
259
—
499, 517, 520, 535
5.40

Mn(asp)₂
226
277
—
544, 568shld, 682, 829
5.82

Na₂[Cu(asp)₂]
226
238
259
667
2.20

Na₂[Cd(asp)₂]
226
241
256
833, 881
0.00

Na₂[Ni(asp)₂]
—
235
259
637, 652
1.15

Na₂[Co(asp)₂]
223
241
256
526, 541, 565
4.33

Na₂[Mn(asp)₂]
223
235
265
526, 541, 673

Figure 2: Infrared spectrum for Na₂[Co(asp)₂].

Figure 3: Infrared spectrum for Na₂[Cu(asp)₂].

3.3. Electronic Spectra and Magnetic Moment

The electronic spectra of the ligands showed three absorption bands at 196, 212, and 232 nm assigned as the , , and transitions of the major chromophores, NH₂ and , present in the ligand molecules. On coordination, however, shifts were observed in these bands in addition to d-d transitions bands (Table 3). These in conjunction with the magnetic moment of the complexes were used to propose probable geometry of the complexes obtained.

Table 3: Relevant IR bands for the compounds.

Band
(NH₂)
(COO⁻)
(COO⁻) (cm⁻¹)
(M–N)
(M–O)

Aspartic acid
3380w
1650s
1583s
—
—

Cu(asp)₂
3433m
1641w
1509w
552s
656m

Cd(asp)₂
3333w
1650s
1539s
549s
724s

Ni(asp)₂
3357w
1674s
1559s
548w
721w

Co(asp)₂
3143br
1684s
1561s
566w
665m

Mn(asp)₂
3309w
1678m
1547w
550s
598m

Na₂[Cu(asp)₂]
3238, 3142br
1678s, 1595m
1503s, 1371s
520m
623br

Na₂[Cd(asp)₂]
3025br
1687s
1532br
598s
619s

Na₂[Ni(asp)₂]
3190w,br
1667sh
1547s
500m
672s

Na₂[Co(asp)₂]
—
1684s, 1584w
1512s, 1375s
546s
604s

Na₂[Mn(asp)₂]
3357br
1686s
1542m
550s
658s

asp: aspartic acid; w: weak; m: medium; s: strong.

3.3.1. Na₂[ML₂] Complexes

The spectrum for the copper(II) complex displayed a well resolved band at 667 nm, Figure 4, assigned as transition, which suggests an octahedral geometry [32]. This proposed geometry was corroborated by its magnetic moment of 2.47 BM, indicative of a tetragonally distorted octahedral geometry [33]. A weak band at 833 nm assigned as charge transfer band was observed in the spectrum for the cadmium(II) complex. This was supported by its magnetic moment of zero, indicative of a diamagnetic Cd(II) complex with filled 4d orbital [32, 33]. The Ni(II) complex exhibited a shoulder at 637 nm and a strong band at 652 nm, which were assigned to and transitions. The magnetic moment of 3.28 BM however is suggestive of an octahedral geometry [34, 35]. The cobalt(II) complex gave a shoulder at 526 nm, a strong band at 541 nm, and a weak band at 565 nm typical of a six coordinate, octahedral geometry for cobalt(II) and were attributed to , , and transitions. This geometry was corroborated by a magnetic moment of 5.40 BM [34–36]. The Mn(II) complex exhibited weak absorption bands at 526, 541, and 673 nm which are consistent with a six-coordinate, octahedral geometry and were assigned to (G), , and   transitions; its magnetic moment of 5.82 BM complements this [2].

Figure 4: UV-Vis spectrum for Na₂[Cu(asp)₂].

3.3.2. ML₂ Complexes

The spectrum for the copper(II) complex displayed two bands at 628 and 667 nm, Figure 5, assigned to and transitions. The complex exhibited a magnetic moment of 2.2 BM indicative of a mononuclear copper(II) complex with 4-coordinate square planar geometry [37–39]. The cadmium complex exhibited no d-d transition band. A magnetic moment of zero corroborates this; however based on valence bond theory a tetrahedral geometry is proposed, and this is in agreement with previous reports [32, 39]. The nickel complex exhibited a well-defined band at 517 nm assigned as . A magnetic moment of 1.15 BM was observed for this complex. This is interpreted as a low spin–high spin equilibrium mixture of tetrahedral-square planar complex [40]. The Co(II) complex exhibited two absorption bands at 499 and 520 nm, assigned as and , respectively, typical for a tetrahedral geometry. This is corroborated by a magnetic moment of 4.33 BM [38]. Bands at 544, 568, and 682 for the Mn(II) complex were assigned to , , and transitions and a charge transfer band at 829 nm [41].

Figure 5: UV-Vis spectrum for Cu(asp)₂.

3.4. Mass Spectrometry

The electronic impact mass spectrum of the complex (Figure 6) was obtained and a probable fragmentation pattern was proposed (Figure 7). The spectrum showed a weak peak at m/z 319 (4%), which coincides with the calculated molecular ion. The fragmentation of the molecular ion was proposed to occur via three pathways, Q, R, and S. Pathway Q corresponds to the loss of β-COOH to give a peak at m/z 274 (9%). Pathway R corresponds to the extrusion of a ligand as a radical to give a peak at m/z 187 (42%). While for pathway S the molecular ion fragments with the ligand as a positive ion with m/z 132 (4%). This ion further fragmented with the loss of COO to yield a peak at m/z 88, the base peak. It also fragmented giving a peak at m/z 70 (92%) with the loss of a water molecule.

Figure 6: Mass spectrum of Mn(asp)₂.

Figure 7: Proposed fragmentation pattern of Mn(asp)₂.

Thus, from the foregoing, it was proposed that the coordination mode of aspartic acid is a function of the pH at which the reaction was carried out, as this may invariably determine the donor atoms of the ligand available for coordination [42, 43]. From previous reports, it has been reported that the participation of a particular functional group in metal binding depends partly on its acid dissociation constant [42]. In this case, aspartic acid has α-carboxylic acid moiety with of 2.09 and a β-carboxylic acid moiety with of 3.86. This implies that for the donor atoms to be readily available for complex formation the pH of the reaction must fall within these ranges. This was evident in the complexes formed; this is because at pH ranges greater than 4.0, both the oxygen donor atoms from the α- and β-carboxylic group were available for binding [9–11]. It therefore acts as a tridentate ligand [9–11, 42].

It is further suggested that energy consideration as a result of the stability of the chelate ring also enhanced the coordination mode of the ligand. This is because although the ion has a value of 9.82 (Figure 8), even at low pH, the nitrogen atom may be used for coordination. Previous studies have shown this to be due to the strong electron-donor (basic) character of the N atom of the NH₂ group and stability of the chelate ring [42–44]. This in addition is supported by the flexibility of the amino acid ligand. It was also observed that the geometry of the complexes was not determined only by the ligand, but the metal ions as well [13, 16–20]. This is because the complexes assume geometries better suited for the metal ions, resulting in the variations observed for some of the complexes.

Figure 8: Coordination behaviour of aspartic acid: a function of the pH of the reaction. (a) In strong acid (below pH 1); net charge = +1. (b) Around pH 3; net charge = 0. (c) Around pH 6–8; net charge = −1. (d) In strong alkali (above pH 11) net charge = −2.

3.5. Antimicrobial

The results obtained indicated that the compounds exhibited a broad spectrum of activity against the tested bacteria and fungi strains and in some cases better activity compared to the standard. Some of the complexes exhibited better activity compared to the ligand, consequently lending support to the chelation theory [2, 26, 45–50]. In line with previous reports the compounds exhibited better activity generally against Gram-positive bacteria. This has been attributed to the increased hydrophobic character of these molecules in crossing the cell membrane of the microorganism. As a consequence, the utilization ratio of the compounds is enhanced [1–6, 26, 45].

Generally the ML₂ complexes exhibited better activity compared to the Na₂[ML₂] complexes with the exception of the copper and manganese complexes. The better activity of the ML₂ complexes compared to the Na₂[ML₂] complexes in some cases may be ascribed to the enhanced lipophilicity of the former as a result of its nonionic nature as against the positively charged latter [2, 26, 45–50]. The Na₂[Cd(asp)₂] complex gave good activity against C. albicans, while Cd(asp)₂ exhibited marginal activity against the fungi (Table 4). This indicates the activity of the metal ion as an antifungal agent. It also points to the fact that enhanced lipophilicity as a result of the tridentate nature of the ligand may increase the activity of the complex [2, 26, 45–50]. It is suggested that the size and number of chelate rings may play a role in the enhanced activity of these compounds in this case. The Cu(asp)₂ complex exhibited the best activity, contrary to that obtained in previous report for similar coordination compounds [24, 26, 51]. The Na₂[Cu(asp)₂] exhibited good activity against S. aureus, indicating the effect of the metal ion as an antimicrobial agent [51]. The activity of some of the complexes against B. subtilis, MRSA, Ps. Aeruginosa, and C. Albicans (Table 4) was significantly higher than the standard drug (). This indicates their potentials as antimicrobial agents against these microbes.

Table 4: Antimicrobial activities of the compounds.

Microorganisms
E. coli
P. aeruginosa
P. vulgaris
S. aureus
B. subtilis
MRSA
C. albicans

Aspartic acid
6.0 ± 0.2
6.0 ± 0.7
6.0 ± 0.0
6.0 ± 0.1
6.0 ± 0.1
6.0 ± 0.5
8.0 ± 1.0

Cu(asp)₂
6.0 ± 0.0
12.0 ± 0.3
6.0 ± 0.2
12.0 ± 0.7
12.0 ± 0.0
16.0 ± 0.5
6.0 ± 0.3

Cd(asp)₂
8.0 ± 0.2
8.0 ± 0.0
6.0 ± 0.6
11.0 ± 0.1
8.0 ± 0.3
11.0 ± 0.0
17.0 ± 0

Ni(asp)₂
6.0 ± 0.5
6.0 ± 0.1
6.0 ± 0.7
6.0 ± 1.0
6.0 ± 0.9
6.0 ± 0.2
6.0 ± 0.2

Co(asp)₂
6.0 ± 0.6
6.0 ± 0.1
6.0 ± 0.1
6.0 ± 0.0
6.0 ± 0.0
6.0 ± 0.8
6.0 ± 0.6

Mn(asp)₂
8.0 ± 0.5
8.0 ± 0.8
8.0 ± 0.3
14.0 ± 0.2
20.0 ± 0.5
10.0 ± 0.3
6.0 ± 0.4

Na₂[Cu(asp)₂]
9.0 ± 1.0
6.0 ± 0.3
10.0 ± 0.7
36.0 ± 0.8
16.0 ± 0.3
23.0 ± 0.8
16.0 ± 0.9

Na₂[Cd(asp)₂]
6.0 ± 0.0
11.0 ± 0.4
6.0 ± 1.0
10.0 ± 0.5
6.0 ± 0.6
6.0 ± 0.3
37.0 ± 0.1

Na₂[Ni(asp)₂]
8.0 ± 0.7
6.0 ± 0.8
6.0 ± 0.4
11.0 ± 0.9
13.0 ± 0.4
18.0 ± 0.3
15.0 ± 0.9

Na₂[Co(asp)₂]
14.0 ± 0.3
6.0 ± 0.5
6.0 ± 1.1
6.0 ± 0.2
10.0 ± 0.2
18.0 ± 0.1
17.0 ± 0.0

Na₂[Mn(asp)₂]
6.0 ± 0.7
6.0 ± 0.9
13.0 ± 0.0
6.0 ± 0.2
6.0 ± 0.7
13.0 ± 0.3
6.0 ± 0.1

C
20.0 ± 0.4
6.0 ± 0.0
15.0 ± 0.6
20.0 ± 0.2
6.0 ± 0.9
6.0 ± 0.7
19.0 ± 0.1

C: Acriflavine.

+: Gram-positive bacteria.

−: Gram-negative bacteria.

4. Conclusion

In this study coordination compounds of aspartic acid were synthesized in both acidic and basic media. It was concluded that the geometry assumed by the synthesized compounds was a function of available donor atoms of the ligand and this is dependent on the relevant pH in which the reaction was carried out. The complexes exhibited a broad spectrum of activity. In some cases complexes synthesized in basic medium exhibited better activity compared to their counterpart complexes obtained in acidic medium. This was attributed to their enhanced lipophilicity as a result of the increased number of chelate rings.

Competing Interests

The authors declare that they have no competing interests.

Acknowledgments

T. O. Aiyelabola is grateful to NWU for a postdoctoral fellowship and the Sasol Inzalo, NRF fellowship.

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