An Adduct of Magnesium Sulfate with a Member of the Quinolone Family (Ciprofloxacin)

Abstract

In the title compound, 4-(3-carboxy-l-cyclopropyl-6 -fluoro-1,4-dihydro -4-oxo-7 -quinolinyl ) -1 -piperazinium-magnesium hexahydrate-sulfate-water(1/0.5/1/3), (Ci7H19FN303)[Mg(H20)6]0.5SOa.3H20, the Mg 2+ ion lies on a twofold axis and adopts a nearly regular octahedral geometry. The quinolone is protonated at the terminal N atom of the piperazine residue. The H atom of the carboxylic acid group is hydrogen bonded to the carbonyl O atom, thus preventing the bonding of the metal to this part of the molecule. CommentThe title quinolone, ciprofloxacin [cf; 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-( 1 -piperazinyl)-3-quinolinecarboxylic acid] is a fluoroquinolone antibacterial agent with a wide spectrum of activity. It is known that the absorption of all quinolones appears to be significantly reduced by magnesium and aluminium antacids. Several other cations interact in a similar manner and the cause is probably chelation between the quinolone and the metal ion (Polk, 1989;Kara, Hasinoff, McKay & Campbell, 1991). Only a few crystal structures between quinolones and different metal ions (Ag +, Co 2+, Cu 2+) have been published

Compounds of Antibacterial Agent Ciprofloxacin and Magnesium – Crystal Structures and Molecular Modeling Calculations

“…In 3, quinolone is protonated and is not able to coordinate to magnesium. [18] Six aqua ligands are coordinated to the metal which is quite common for magnesium ions. [32] Under hydrothermal conditions in basic medium a polymeric complex 4 forms.…”

“…Formula of cfH (a) and its various forms present in crystal structures. Protonated form cfH 2 + (b), showing also the intramolecular hydrogen bond (present for example in ciprofloxacin hydrochloride [35] and 3 [18] ). Anionic form (c) (present for example in 4 [13] ).…”

“…[18,35,36] Typical examples containing the protonated ligand are 3 and (cfH 2 )(cfH 3 )[CuCl 4 ]-Cl·H 2 O (5). [36] The charge of quinolone in 3 is 1+ since the terminal nitrogen atom of the piperazine ring is protonated but also hydrogen is bonded to the oxygen atom of the carboxylic group (see Scheme 3, b).…”

Effect of metal ions on the in vitro availability of enoxacin, its in vivo implications, kinetic and antibacterial studies

“…15,16 Here in we also propose that ionic interaction existed between the drug and metal ion in acidic medium. At low pH, the ring carbonyl oxygen of enoxacin is protonated 17 or the hydrogen atom of the carboxylic group is hydrogen bonded to the carbonyl oxygen atom, 18 giving it a partial positive charge. As the carboxylic group is not deprotonated, the consequence is that this part of the molecule is unable to bind to the metal (no significant shift of the absorption peak of Chromophore II).…”

Synthesis, characterization and DNA binding of magnesium–ciprofloxacin (cfH) complex [Mg(cf)2]·2.5H2O

“…Up to now only few magnesium-quinolone crystal structures have appeared in the literature though it is well known that magnesium ions are important for the activity of these drugs [13][14][15]. The exact role of magnesium ions in the interaction between quinolone, DNA and DNA-gyrase is also not known yet and several models were proposed to explain the mechanism of action [16][17][18][19].…”