Stability constants of ternary complexes β-lactam antibiotic drugs with bivalent transition metal(II) ions in the presence of aliphatic amino acids

Abstract

Metal complex structures are important in many biological processes where coordination can occur between various metal ions and a wide variety of ligands. Here we compared bivalent transition metal(II) ions- ternary complexes with penicillin class amoxicillin and cephalosporin class cefaclor actives in the presence of aliphatic amino acids. The complex formation conditions and compositions of the complexes formed by the classical, economical and reproducible Irving-Rossotti method were investigated. Therefore, the formation conditions and compositions of binary and ternary complexes were investigated by the Irving Rossotti procedure. Ternary complexes are prepared by mixing metal(II) with active ingredients and the appropriate amount of primary ligand or L-asparagine (ASP) or L-glutamic acid (Glut). In the ternary systems, ASP and Glut are primary ligands (L) whereas amoxicillin (Amox) and cefaclor (Cefa) behave as a secondary ligand (Y). From the calculated formation constants of the complexes formed by the selected blactam antibiotics and amino acids with Cu(II) and Zn(II) metals, it was determined that the metal-ligand mole ratios were 1:1:1 (M:L:Y). At room temperature, the formation constants of the complexes were found by adjusting the ionic strength to 0.11 mol dm-3 with NaCIO4: logb(Cu(II)-ASP-Amox)=15.83±0.01; logb (Cu(II)-Glut-Amox)=20.76±0.01; logb(Cu(II)-ASPCefa)= 16.59±0.01; logb(Cu(II)-Glut-Cefa)=5.72±0.01; logb(Zn(II)-ASP-Amox)=5.32±0.01; logb(Zn(II)-Glut-Amox)=4.62±0.01; logb(Zn(II)-ASPCefa)= 5.46±0.01; logb(Zn(II)-Glut-Cefa)=4.52±0.01 respectively. The relative stabilities of the ternary complexes (ΔlogK) were interpreted by comparison with the stabilities of the corresponding binary complexes, with negative ΔlogK values observed for all complexes.

Keywords

• Amoxicillin
• Cefaclor
• L-asparagine
• L-glutamic acid
• Ternary complex

References

1. [1] Sorenson JRJ. Copper complexes offer a physiological approach to treatment of chronic diseases. Prog Med Chem. 1989; 26: 437–568. https://doi.org/10.1016/s0079-6468(08)70246-7.
2. [2] Chohan ZH, Supuran CT, Scozzafava A. Metalloantibiotics: synthesis and antibacterial activity of cobalt(II), copper(II), nickel(II) and zinc(II) complexes of kefzol. J Enzyme Inhib Med Chem. 2004;19(1):79-84. https://doi.org/10.1080/14756360310001624939.
3. [3] Dimitrovska A, Andonovski B, Stojanoski K. Spectrophotometric study of copper(II) ion complexes with cefaclor. Int J Pharm. 1996; 134; 213-221.
4. [4] Noor N, Humayoun S, Zafar H, Lakhnana NK, Bukhari KT. Meta-analysis to assess role of systemic antibiotics in root canal treatment. J Pharm Biol Sci 2017; 38-46. https://doi.org/10.20510/ukjpb/5/i4/166543.
5. [5] Hansmann Y. Treatment and prevention of Lyme disease. Curr Probl Dermatol. 2009;37:111-129. https://doi.org/10.1159/000213071.
6. [6] Kuriyama T, Williams DW, Yanagisawa M, Iwahara K, Shimizu C, Nakagawa K, Yamamoto E, Karasawa T. Antimicrobial susceptibility of 800 anaerobic isolates from patients with dentoalveolar infection to 13 oral antibiotics. Oral Microbiol Immunol. 2007; 22(4): 285-288. https://doi.org/10.1111/j.1399-302X.2007.00365.x
7. [7] Drissi M, Ahmed ZB, Dehecq B, Bakour R, Plesiat P, Hocquet D. Antibiotic susceptibility and mechanisms of β lactam resistance among clinical strains of Pseudomonas aeruginosa: First report in Algeria. Med Mal Infect. 2008; 38(4): 187-191. https://doi.org/10.1016/j.medmal.2008.01.009.
8. [8] Handal T, Olsen I, Walker CB, Caugant DA. Detection and characterization of β-lactamase genes in subgingival bacteria from patients with refractory periodontitis. FEMS Microbiol Lett. 2005; 242(2): 319-324. https://doi.org/10.1016/j.femsle.2004.11.023.

9. [9] Mandsberg LF, Ciofu O, Kirkby N, Christiansen LE, Poulsen HE, Høiby N. Antibiotic resistance in Pseudomonas aeruginosa strains with increased mutation frequency due to inactivation of the DNA oxidative repair system. Antimicrob Agents Chemother. 2009; 53(6): 2483-2491. https://doi.org/10.1128/AAC.00428-08.
10. [10] Bisson-Boutelliez C, Fontanay S, Finance C, Kedzierewicz F. Preparation and physicochemical characterization of amoxicillin β-cyclodextrin complexes. AAPS PharmSciTech. 2010; 11: 574-581. https://doi.org/ 10.1208/s12249 010-9412-1.
11. [11] Voha C, Docquier JD, Rossolini GM, Fosse T. Genetic and biochemical characterization of FUS-1 (OXA-85), a narrow-spectrum class D β-lactamase from Fusobacterium nucleatum subsp. polymorphum. Antimicrob Agents Chemother. 2006; 50(8): 2673-2679. https://doi.org/10.1128/AAC.00058-06.
12. [12] Marukhlenko AV, Morozova MA, Mbarga A, Antipova, NV, Syroeshkin AV, Podoprigor IV, Maksimova TV. Chelation of zinc with biogenic amino acids: Description of properties using balaban index, assessment of biological activity on spirostomum ambiguum cellular biosensor, influence on biofilms and direct antibacterial action. Pharmaceuticals. 2022; 15(8): 979. https://doi.org/10.3390/ph15080979.
13. [13] Kurpad AV. The requirements of protein & amino acid during acute & chronic infections. Indian J Med Res. 2006; 124(2): 129-148.
14. [14] Darwin KH. Mycobacterium tuberculosis and copper: a newly appreciated defense against an old foe? J Biol Chem. 2015; 290(31): 18962-18966. https://doi.org/10.1074/jbc.R115.640193.
15. [15] Lapshin SV, Alekseev VG. Copper (II) complexation with ampicillin, amoxicillin, and cephalexin. Russ J Inorg Chem. 2009; 54: 1066–1069. https://doi.org/10.1134/S0036023609070122.
16. [16] Cardiano P, Crea F, Foti C, Giuffrè O, Sammartano S. Potentiometric, UV and 1H NMR study on the interaction of Cu2+ with ampicillin and amoxicillin in aqueous solution. Biophys Chem. 2017; 224: 59-66. https://doi.org/ 10.1016/j.bpc.2017.04.001.
17. [17] Shoukry MM. Potentiometric studies of binary and ternary complexes of amoxicillin. Talanta. 1992; 39(12): 1625 1628. https://doi.org/10.1016/0039-9140(92)80194-I.
18. [18] Mwene-Mbeja TM. Chemical Stability of Pharmaceutical Organic Compounds. Am J Biomed Sci Res. 2019; 6(1): 14 22. https://doi.org/10.34297/AJBSR.2019.06.000984.
19. [19] Imran M, Iqbal J, Mehmood T, Latif S. Synthesis, characterization and in vitro screening of amoxicillin and its complexes with Ag(I), Cu(II), Co(II), Zn(II) and Ni(II). J Biol Sci. 2006; 6: 946 949. https://doi.org/10.3923/jbs.2006.946.949
20. [20] Butler JN. Ionic Equilibrium a Mathematical Approach. Addison‐Wesley Publishing Company Inc., London, 1964. https://doi.org/10.1002/bbpc.19640680523.
21. [21] Martell AE, Hancock RD. Metal Complexes in Aqueous Solutions. Springer New York NY, 1996. https://doi.org/10.1007/978-1-4899-1486-6.
22. [22] Tran-Ho LC, May PM, Hefter GT. Complexation of Copper(I) by Thioamino acids. Implications for copper speciation in blood plasma. J Inorg Biochem. 1997; 68(3): 225-231. https://doi.org/10.1016/S0162-0134(97)00097-4.
23. [23] Dogan A, Köseoglu F, Kiliç E. The stability constants of copper (II) complexes with some alpha-amino acids in dioxane–water mixtures. Anal Biochem. 2001; 295(2): 237-239. https://doi.org/10.1006/abio.2001.5205.
24. [24] Iqbal MS, Bukhari IH, Arif M. Preparation, characterization and biological evaluation of copper (II) and zinc (II) complexes with Schiff bases derived from amoxicillin and cephalexin. Appl Organomet Chem. 2005; 19(7): 864-869. https://doi.org/10.1002/aoc.918
25. [25] Hrioua A, Loudiki A, Farahi A, Laghrib F, Bakasse M, Lahrich S, Saqrane S, El Mhammedi MA. Complexation of amoxicillin by transition metals: Physico-chemical and antibacterial activity evaluation. Bioelectrochemistry. 2021; 142: 107936. https://doi.org/10.1016/j.bioelechem.2021.107936
26. [26] Al-Noor TH, Aziz MR, AL-Jeboori AT. Synthesis, characterization and antimicrobial activities of [Fe(II), Co(II), Ni(II),Cu(II) and Zn(II)] mixed ligand complexes schiff base derived from amoxicillin drug and 4 (dimethylamino)benzaldehyde with nicotinamide. J Chem Pharm Res. 2014; 6(4): 1225-1231.
27. [27] Demir HD, Pekin M, Cucu AK, Dolen E, Aboul-Enein HY. Potentiometric studies of mixed complexes of cobalt (II) and copper (II) with l‐Asparagine and adenine. Toxicol Environ Chem. 1999; 71(3-4): 357-367. https://doi.org/10.1080/02772249909358806.
28. [28] Ammar RA, Al-Mutiri EM, Abdalla MA. The determination of the stability constants of mixed ligand complexes of adenine and amino acids with Ni(II) by potentiometric titration method. Fluid Phase Equilib. 2011; 301(1): 51-55. https://doi.org/10.1016/j.fluid.2010.11.014.
29. [29] Al-Mohaimeed AM, Alothman AA. Characterization by potentiometric procedures of the stability constants of the binary and ternary complexes of Cu (II) and duloxetine drug with amino acids. J Chem. 2019; https://doi.org/10.1155/2019/1064942.
30. [30] Abdelkarim AT, Mahmoud WH, El-Sherif AA. Potentiometric, thermodynamics and coordination properties for binary and mixed ligand complexes of copper(II) with cephradine antibiotic and some N- and O-bound amino acids (α-alanine and β-alanine). J Mol Liq. 2021; 328: 115334. https://doi.org/10.1016/j.molliq.2021.115334.
31. [31] Orabi AS, Abbas AM, Abd Elraoof MA, Khairy GM. Modern view for binary and ternary complexes of metal ions with amoxicillin and some amino acids. Adv Environ Life Sci. 2022; 1: 22-39. https://doi.org/10.21608/aels.2021.111628.1002.
32. [32] Karaderi S, Bilgic D. Zinc(II) and Cadmium(II) binary complexes with creatinine and their mixed-ligand complexes with L-Asparagine or L-Glutamic Acid: Potentiometric studies. Main Group Met Chem. 2006; 29(3): 145-156. https://doi.org/10.1515/mgmc.2006.29.3.145.
33. [33] Bartaria D, Chandra P, Krishna V. A study on speciation and coordination tendency of glutamic acid and uracil for ternary complexation towards some toxic metal ions. Chem Sci Revie Lett. 2013; 1201-1208.
34. [34] Irving HM, Rossotti HS.The calculation of formation curves of metal complexes from pH titration curves in mixed solvents. J Chem Soc. (Resumed). 1954; 2904-2910. https://doi.org/10.1039/JR9530003397.
35. [35] Irving HM, Miles MG, Pettit LD. A study of some problems in determining the stoicheiometric proton dissociation constants of complexes by potentiometric titrations using a glass electrode. Anal Chim Acta. 1967; 38: 475-488. https://doi.org/10.1016/S0003-2670(01)80616-4.
36. [36] Alkaya B, Karaderi S, Erdoğan G. Ternary complex formation of isoniazid wıth some transition metals and amino acids. Trakya Univ J Nat Sci. 2013; 14(1): 1-14.
37. [37] Zinnat A, Begum Ismail, MM, Rahman Tsugiko Takase, Hiroshi Hasegawa. Formation and stability of the mixed chelator complexes of Sr2+, Mg2+, Ca2+, Ba2+, and Y3+ in solution with bio-relevant chelators. J Inorg Biochem. 2019; 195: 141-148. https://doi.org/10.1016/j.jinorgbio.2019.03.018.