Binding of ciprofloxacin by humic substances: A molecular dynamics study

Abstract

A comprehensive assessment of the potential impacts of antimicrobials released into the environment requires an understanding of their sequestration by natural particles. Of particular interest are the strong interactions of antimicrobials with natural organic matter (NOM), which are believed to reduce their bioavailability, retard their abiotic and biotic degradation, and facilitate their persistence in soils and aquatic sediments. Molecular dynamics (MD) relaxation studies of a widely used fluoroquinolone antibiotic, ciprofloxacin (Cipro), interacting with a model humic substance (HS) in a hydrated environment, were performed to elucidate the mechanisms of these interactions. Specifically, a zwitterionic Cipro molecule, the predominant species at circumneutral pH, was reacted either with protonated HS or deprotonated HS bearing Ca, Mg, or Fe(II) cations. The HS underwent conformational changes through rearrangements of its hydrophobic and hydrophilic regions and disruption of its intramolecular H-bonds to facilitate favorable intermolecular H-bonding interactions with Cipro. Complexation of the metal cations with HS carboxylates appeared to impede binding of the positively charged amino group of Cipro with these negatively charged HS complexation sites. On the other hand, an outer-sphere complex between Cipro and the HS-bound cation led to ternary Cipro-metal-HS complexes in the case of Mg-HS and Fe(II)-HS, but no such bridging interaction occurred with Ca-HS. The results suggested that the ionic potential (valence/ionic radius) of the divalent cation may be a determining factor in the formation of the ternary complex, with high ionic potential favoring the bridging interaction. Environ. Toxicol. Chem. 2010;29:90-98. (c) 2009 SETAC.

Molecular modeling of soil organic matter: Squaring the circle?

“…Interestingly, the hydrophilic character, porosity and surface area of a DOM molecule was increased upon insertion of fully hydrated cations such as Na + and Ca 2+ , indicating a structure relaxation upon deprotonation (Sutton et al, 2005). Complexation of metal cations appeared to impede binding of xenobiotic anions but enabled outersphere ternary xenobiotic-metal-HS complexes (Aristilde and Sposito, 2010). Molecular mechanics calculation of organo-mineral associations revealed that hydrogen-bonding of humic substances to the mineral sites is subordinate, while metal-cation-bridges (Fe 3+ , Al 3+ ) dominated (Schulten and Schnitzer, 1997).…”

“…Alternatively, this technical problem is overcome selecting an alternative force field. Recently model calculations were done using semiempirical quantum mechanics calculations by the complete neglect of differential overlap (CNDO) method (Pople and Beveridge, 1970) or employing molecular dynamics with the COMPASS force field, thus widening the applicability of the large humic-molecules to dynamic studies including ionic species (Aristilde and Sposito, 2010;Schulten and Leinweber, 2000;Sutton et al, 2005). 4.…”

Occurrence and fate of eleven classes of antibiotics in two typical wastewater treatment plants in South China

“…The high mass load of the fluoroquinolones in the dewatered sludge resulted from the long-term cycling and accumulation of the fluoroquinolones during activated sludge treatment, due to the strong adsorption of fluoroquinolones. The solubilities of fluoroquinolones are low (Table S1) and they can interact strongly with clay, nature organic matter and metal oxides (Aristilde and Sposito, 2010;Pei et al, 2010) (Table S1). It is obvious that adsorption onto sludge is an important aqueous phase removal mechanism for the fluoroquinolones in a WWTP.…”

Sorption of Enrofloxacin and Ciprofloxacin in Agricultural Soils: Effect of Organic Matter

“…), much weaker polar interactions between the uncharged regions of the FQs and HA can also take place, such as H bonding (e.g. between the FQ-dissociated carboxyl and a HA-protonated amino group) or Van der Waals (Aristilde and Sposito 2010;Pignatello 2011).…”