Environmental Science and Pollution Research

, Volume 25, Issue 5, pp 4279–4288 | Cite as

Cu(II)-catalyzed degradation of ampicillin: effect of pH and dissolved oxygen

  • Yiming Guo
  • Daniel C. W. Tsang
  • Xinran ZhangEmail author
  • Xin YangEmail author
Research Article


Cu(II)-catalyzed hydrolysis of β-lactam antibiotics has been well-identified and recognized as the key mechanism of antibiotic degradation. However, the overlooked Cu(II) oxidation susceptibly also plays an important role comparably with hydrolysis. This study evaluated the roles of hydrolysis and oxidation in Cu(II)-catalyzed degraded ampicillin (AMP), as a typical β-lactam antibiotic, under relevant environmental conditions (pH 5.0, 7.0, and 9.0; oxygen 0.2 and 6.2 mg/L). Under AMP and Cu(II) molar ratio of 1:1, AMP degradation was the fastest at pH 9.0, followed by pH 5.0 and pH 7.0. The facilitation of oxygen on AMP degradation was notable at pH 5.0 and 7.0 rather than pH 9.0. AMP degradation rate increased from 21.8% in 0.2 mg/L O2 solution to 85.9% in 6.2 mg/L O2 solution at pH 7.0 after 4-h reaction. AMP oxidation was attributed to both oxygen-derived Cu(I)/Cu(II) cycle and intermediate reactive oxygen species (HO. and O2 .−). Several intermediate and final products in AMP degradation were firstly identified by LC-quadrupole time-of-flight-MS analysis. Phenylglycine primary amine on the AMP structure was the essential complexation site to proceed with the oxidation reaction. The oxidation of AMP preferentially occurred on the β-lactam structure. The inherent mechanisms related to pH and oxygen conditions were firstly investigated, which could enhance the understanding of both oxidation and hydrolysis mechanisms in AMP degradation. This study not only has an important implication in predicting β-lactam antibiotic transformation and fate in natural environment but also benefits the developing of strategies of antibiotic control to reduce the environmental risk.


β-Lactam antibiotics Ampicillin Copper redox Complexation Oxidation Hydrolysis 


Funding information

We thank the National Basic Research Program of China (grant 2015CB459000), National Science Foundation of China (grants 21577178 and 21622706), Guangdong’s Natural Science Funds for Distinguished Young Scholars (grant 2015A030306017), and Fundamental Research Funds for the Central Universities (grant 17lgpy93) for their financial support of this study.

Supplementary material

11356_2017_524_MOESM1_ESM.docx (1.5 mb)
ESM 1 (DOCX 1553 kb)


  1. Alekseev VG (2012) Metal complexes of penicillins and cephalosporins (review). Pharm Chem J 45:679–697CrossRefGoogle Scholar
  2. Blaha JM, Knevel AM, Kessler DP, Mincy JW, Hem SL (1976) Kinetic analysis of penicillin degradation in acidic media. J Pharm Sci 65:1165–1170CrossRefGoogle Scholar
  3. Carabineiro SAC, Thavorn-Amornsri T, Pereira MFR, Figueiredo JL (2011) Adsorption of ciprofloxacin on surface-modified carbon materials. Water Res 45:4583–4591CrossRefGoogle Scholar
  4. Carabineiro SAC, Thavorn-Amornsri T, Pereira MFR, Serp P, Figueiredo JL (2012) Comparison between activated carbon, carbon xerogel and carbon nanotubes for the adsorption of the antibiotic ciprofloxacin. Catal Today 186:29–34CrossRefGoogle Scholar
  5. Chen J, Sun P, Zhang Y, Huang CH (2016) Multiple roles of Cu(II) in catalyzing hydrolysis and oxidation of beta-lactam antibiotics. Environ Sci Technol 50:12156–12165CrossRefGoogle Scholar
  6. Chen J, Sun P, Zhou X, Zhang Y, Huang CH (2015) Cu(II)-catalyzed transformation of benzylpenicillin revisited: the overlooked oxidation. Environ Sci Technol 49:4218–4225CrossRefGoogle Scholar
  7. Chen WR, Huang CH (2009) Transformation of Tetracyclines mediated by Mn(II) and Cu(II) ions in the presence of oxygen. Environ Sci Technol 43:401–407CrossRefGoogle Scholar
  8. Clarke EGC, Moffat AC, Jackson JV, Moss MS, Widdop B (1986) Clarke’s isolation and identification of drugs in pharmaceuticals, body fluids, and post-mortem material, 2nd edn. The Pharmaceutical Press, LondonGoogle Scholar
  9. Cressman WA, Sugita ET, Doluisio JT, Niebergall PJ (1969) Cupric ion-catalyzed hydrolysis of penicillins: mechanism and site of complexation. J Pharm Sci 58:1471–1476CrossRefGoogle Scholar
  10. Dimitrovska A, Andonovski B, Stojanoski K (1996) Spectrophotometric study of copper(II) ion complexes with cefaclor. Int J Pharm 134:213–221CrossRefGoogle Scholar
  11. Dodd MC, Shah AD, von Gunten U, Huang CH (2005) Interactions of fluoroquinolone antibacterial agents with aqueous chlorine: reaction kinetics, mechanisms, and transformation pathways. Environ Sci Technol 39:7065–7076CrossRefGoogle Scholar
  12. Fernandez-Gonzalez A, Badia R, Diaz-Garcia ME (2005) Insights into the reaction of beta-lactam antibiotics with copper(II) ions in aqueous and micellar media: kinetic and spectrometric studies. Anal Biochem 341:113–121CrossRefGoogle Scholar
  13. Gensmantel NP, Proctor P, Page MI (1980) Metal-ion catalysed hydrolysis of some β-lactam antibiotics. J Chem Soc Perkin Trans 11:1725–1732CrossRefGoogle Scholar
  14. Gunther G (1950) The disintegration of penicillin in the presence of heavy metals. Die Pharmazie 5:577–582Google Scholar
  15. Hou JP, Poole JW (1971) β-Lactam antibiotics: their physicochemical properties and biological activities in relation to structure. J Pharm Sci 60:503–532CrossRefGoogle Scholar
  16. Huber MM, Canonica S, Gunyoung Park A, von Gunten U (2003) Oxidation of pharmaceuticals during ozonation and advanced oxidation processes. Environ Sci Technol 37:1016–1024CrossRefGoogle Scholar
  17. Lapshin SV, Alekseev VG (2009) Copper(II) complexation with ampicillin, amoxicillin, and cephalexin. Russ J Inorg Chem 54:1066–1069CrossRefGoogle Scholar
  18. Li B, Zhang T (2010) Biodegradation and adsorption of antibiotics in the activated sludge process. Environ Sci Technol 44:3468–3473CrossRefGoogle Scholar
  19. Robinson-Fuentes VA, Jefferies TM, Branch SK (1997) Degradation pathways of ampicillin in alkaline solutions. J Pharm Pharmacol 49:843–851CrossRefGoogle Scholar
  20. Rodriguez-Mozaz S, Chamorro S, Marti E, Huerta B, Gros M, Sanchez-Melsio A, Borrego CM, Barcelo D, Balcazar JL (2015) Occurrence of antibiotics and antibiotic resistance genes in hospital and urban wastewaters and their impact on the receiving river. Water Res 69:234–242CrossRefGoogle Scholar
  21. Sharma VK, Johnson N, Cizmas L, McDonald TJ, Kim H (2016) A review of the influence of treatment strategies on antibiotic resistant bacteria and antibiotic resistance genes. Chemosphere 150:702–714CrossRefGoogle Scholar
  22. Subbiah M, Mitchell SM, Ullman JL, Call DR (2011) Beta-lactams and florfenicol antibiotics remain bioactive in soils while ciprofloxacin, neomycin, and tetracycline are neutralized. Appl Environ Microbiol 77:7255–7260CrossRefGoogle Scholar
  23. Tim ADB, Weber FA, Bergmann A, Hickmann S, Ebert I, Hein A, Kuster A (2016) Pharmaceuticals in the environment-global occurrences and perspectives. Environ Toxicol Chem 35:823–835CrossRefGoogle Scholar
  24. Van Boeckel TP, Gandra S, Ashok A, Caudron Q, Grenfell BT, Levin SA, Laxminarayan R (2014) Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data. Lancet Infect Dis 14:742–750CrossRefGoogle Scholar
  25. Watkinson AJ, Murby EJ, Kolpin DW, Costanzo SD (2009) The occurrence of antibiotics in an urban watershed: from wastewater to drinking water. Sci Total Environ 407:2711–2723CrossRefGoogle Scholar
  26. Yuan X, Pham AN, Xing G (2012) Effects of pH, chloride, and bicarbonate on cu(I) oxidation kinetics at circumneutral pH. Environ Sci Technol 46:1527–1535CrossRefGoogle Scholar
  27. Zhang QQ, Ying GG, Pan CG, Liu YS, Zhao JL (2015) Comprehensive evaluation of antibiotics emission and fate in the river basins of China: source analysis, multimedia modeling, and linkage to bacterial resistance. Environ Sci Technol 49:6772–6782CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.School of Environmental Science and EngineeringSun Yat-sen UniversityGuangzhouChina
  2. 2.Guangdong Provincial Key Laboratory of Environmental Pollution Control and Remediation TechnologyGuangzhouChina
  3. 3.Department of Civil and Environmental EngineeringThe Hong Kong Polytechnic UniversityKowloonHong Kong, China

Personalised recommendations