КООРДИНАЦИОННАЯ ХИМИЯ, 2010, том 36, № 2, с. 130-137
УДК 541.49
ANTIMICROBIAL ACTIVITY AND DENSITY FUNCTIONAL CALCULATIONS OF A SUPRAMOLECULAR MANGANESE COMPLEX
© 2010 C. Y. Shao1, L. R. Yang1*, S. Song, C. F. Bi2, S. W. Xia2, H. T. Lu3, Z. W. Bu1,
T. G. Ren1, and R. J. Tao1
1Institute of Molecule and Crystal Engineering, College of Chemistry and Chemical Engineering, Henan University, Kaifeng city, P.R. China 2 College of Chemistry and Chemical Engineering, Ocean University of China, Qingdao city, P.R. China 3The Second Middle School of Xihe County, Gansu, P.R. China *E-mail: lirongyang_2005@yahoo.com.cn Received April 4, 2009
The density functional theory calculations on the manganese complex ([Mn(8-OHQ)3] • CH3OH, 8-OHQ = 8-hydroxyquinoline) is made and its stabilization, molecular orbital composition, orbital energies, and NBO charge distribution have been investigated. The crystal structure of the complex closely resembles the optimized structure. In vittv activities against some antimicrobials (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Bacillus subtilis) are determined. The antimicrobial activities present a positive correlation between the concentrations and bioactivities of the complex. The relationship between bioactivities and molecular orbitals (HOMO and LUMO orbitals) of the complex is also discussed.
INTRODUCTION
Being required as a cofactor for a large number of enzymes and manganese-containing proteins, manganese is an essential element in the metabolic processes of organisms as a micronutrient. It also affects the central nervous system and causes the disordering manganism [1]. Evidences support that two manganese atoms (an efficient donor to photosystem II (PSII) locate in each reaction center of PSII to act on its mutant [2, 3]. The manganese cation in its complex disrupts membrane dynamics along the secretory pathway [4]. Complex [Mn2(II,II)(Bpmp)-(^-OAc)2] • ClO4 (Bpmp = 2,6-bis,[bis,(2-pyridylmethyl) aminomethyl]-4-methyl-phenol) exhibits a new model in the natural photosystem of Tyrz and His190. The higher oxidation state of manganese(III) plays an important role in the oxidative process [5].
Studies on the biological activities of manganese complexes against fungi and bacteria are appealing. It was reported by Singh that the complex [Mn(HSTB)3] (HSTB = salicylaldehyde thiobenzhydrazone) strongly inhibits the growth of Staphylococcus (S.) aureus, Staphy-ococcus (S.) epidermidis, and Pseudomonas (P.) aeruginosa [6]. Some other antibacterial screening data showed that manganese metallacrown ethers are more active than the simple, manganese-based herbicide or carboxy-late complexes [7]. Manganese complexes were assayed in vitro for their ability to inhibit the growth of representative gram-positive (S. aureus and Bacillus (B.) poly-myxa) and gram-negative (Escherichia (E.) coli) bacteria and the fungus Candida (C.) albicans, and some certain strains of bacteria and fungus are susceptible to the manganese complexes discussed [8].
In our work, we synthesized, and characterized the manganese complex [Mn(8-OHQ)3] • CH3OH (I) (8-OHQ = 8-hydroxyquinoline). Based on experimental results, we have chosen density functional theory (DFT) calculations on the proposed complex and discussed the stabilization, molecular orbital composition, orbital energies, and natural bond orbital (NBO) charge distribution and compared the theoretical calculation values with experimental data. Subsequently, we tested the antimicrobial activities of the complex and studied the relationship between the structure and bioactivities.
EXPERIMENTAL
For characterization, physical measurements, synthesis of the complex, X-ray crystallographic determination, and thermal decomposition kinetics studies using the Achar differential method and the Coats-Redfern integral method [9], were carried out.
Qualitative antimicrobial assay. Four target pathogenic microorganisms were used to test the biological potential of the complex. Microbials to be tested were E. coli, S. aureus, P. aeruginosa, and B. subtilis. All thalli were from the National Institute for control ofPharmaceutical and Biological Products.
S. aureus, E. coli, P. aeruginosa, and B. subtilis were cultured by inoculating in beef broth (which were sterilized by autoclaving at 121°C for 20 min) and incubating at 37°C for 24 h. Agar culture medium was prepared by dissolving peptone, beef broth, agara, and sodium chloride in distilled water and adjusted to pH 7.2—7.4, which were sterilized by autoclaving at 121°C for 20 min. Cultured E. coli, S. aureus, P. aeruginosa, and B. subtilis were
added to the warm nutrient agar, which were poured into a plate, and allowed to set in the refrigerator for at least 6 h. Filter paper discs of 6-mm diameter were impregnated with a stock solution of the complex (under a series of concentrations) and dried under sterile conditions, which were then placed on the previously inoculated agar surface.
The agar plates were incubated at 37°C overnight allowing the microorganisms to grow where possible. Digital calipers were used to measure the diameter of the area of inhibition around the filter paper discs [10].
Computational methods. All calculations were performed with the Gaussian 03 software package on a Pentium 2.6 computer using the default convergence criteria. We applied the DFT method of B3LYP, 6-31G(d), and 6-31G(d,^) basis sets for C, H, O, N, and effective core potential (ECP) and LANL2DZ for the electrons of manganese atom to optimized the geometry of the proposed structures of [Mn(8-OHQ)3] • CH3OH. Furthermore, NBO analyses were performed on the optimized structure. Atom coordinates for calculations were adopted from crystal structure data. Fifty two atoms, 520 atomic basic functions, and 1049 initial Gaussian functions were involved in the calculations.
RESULTS AND DISCUSSION
The reaction of 8-OHQ with manganese acetate in refluxing methanol gave a deep brown crystalline complex, whose physicochemical properties were determined by some physical measurements, and they supported the formulations of complex I. It forms a three-dimensional supramolecular structure. The complex is mildly soluble in most organic solvents but diffluent in donor solvents, such as DMSO, DMF, and water. It also appears stable in air.
Antimicrobial activities. The manganese complex has been assayed against selected pathogens to evaluate its antimicrobial properties. The data collected in Table 1 indicate that the complex is incoordinately active toward all most of the microorganisms chosen. The values for S. au-reus are more higher than those for the other three microorganisms, suggesting that the complex is observably active against S. aureus, so much as the complex being moderately active at diluent concentrations (e.g., 0.001 mg/ml and 0.0001 mg/ml). We can also conclude that the complex I shows moderately antimicrobial activities against E. coli, and B. subtilis and weak activity toward P. aeruginosa. It appears in Table 1 that a positive correlation is observed between the concentrations and bioactivities of the complex I, such as with the decreasement of the concentrations, its antimicrobial activities diminishes gradually. As a result, the title complex I is an efficient and selective inhibitor against S. aureus. Control experiments have been made using the ligand against the four microorganisms under the same conditions. The antimicrobial activities of the complex I are remarkably efficient than those of its ligand, which proves that metal ions bear indispensably function, to some extent, suggesting that the
Table 1. In vitro qualitative antimicrobial assay results of complex I
Concentration, mg/ml Diameter of zone, mm*
S. aureus E. coli P. aeruginosa B. subtilis
10 19.4 ± 0.2 16.1 ± 0.4 11.4 ± 0.2 14.5 ± 0.2
1 18.7 ± 0.1 15.3 ± 0.2 10.0 ± 0.3 13.2 ± 0.2
0.1 18.2 ± 0.1 13.9 ± 0.5 11.6 ± 0.2
0.01 16.1 ± 0.2 11.3 ± 0.3 10.1 ± 0.4
0.001 14.3 ± 0.5 10.2 ± 0.2
0.0001 10.9 ± 0.4
0.00001
* Diameter of the filter paper discs (R, mm) is <10, inactive; 11 < R < 16 (10 < R < 15), moderately active; R > 16, highly active.
central manganese ion promotes the bioactivity of the complex. The result is in agreement with respective literature [11].
The heteroatom-containing ligand, such as 8-OHQ, exhibits planar conjugation configuration, which may improve the matching performance of the complex with the active sites on the acceptor in the microorganisms at the aspects of steric and electronic effects ascribing to its lipophilicity and permeation ability through cell envelope. Herewith, acting as a certain kind of carrier, the ligand carries an effective dose ofmanganese atoms to the target sites to combine with, which may interfere the natural biological functions of the microorganisms.
Equilibrium geometry structure. Comparison between the main geometry parameters (bond lengths, bond orders, bond angles, and dihedral angles) in the optimized structure I and experimental data are listed in Table 2, suggesting that they are accurately approximate. The optimized structure and the experimental structure of complex I, with the atom numbering is shown in Fig. 1. Figure 2 shows a perspective view of the crystal packing in the unit cell of complex I. Some selected single-crystal X-ray diffraction data together with the optimized geometrical parameters at the B3LYP/6-31G* level are listed in Table 3.
The optimized structure indicates that each molecule of 8-OHQ coordinates to the manganese atom with the N atom and O atom (deprotoned) to form a distorted octahedron geometry. Data of the bond orders elucidate that the lower bond orders of Mn—O and Mn—N have formed in the complex (average bond orders: Mn—O 0.3921 and Mn-N 0.2682). The decrease ofbond orders of O(2)-C(13), O(3)-C(22), and O(4)-C(31) (0.9498, 0.9680, and 0.9790, respectively) implies that C-O in the quinoline ring weakened after the formati
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