CHARACTERIZATION OF THE COMPLEXATION OF FLUOROQUINOLONE ANTIMICROBIALS WITH METAL-IONS BY NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY

被引:51
作者
RILEY, CM [1 ]
ROSS, DL [1 ]
VANDERVELDE, D [1 ]
TAKUSAGAWA, F [1 ]
机构
[1] UNIV KANSAS,DEPT CHEM,LAWRENCE,KS 66045
关键词
C-13-NMR; H-1-NMR; X-RAY CRYSTALLOGRAPHY; FLUOROQUINOLONES; ALUMINUM; MAGNESIUM; COMPLEXATION; CRYSTAL STRUCTURE; MOLECULAR MODELING;
D O I
10.1016/0731-7085(93)80148-T
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
The complexation of the fluoroquinolone antimicrobials is important because it has been implicated in reduced oral bioavailability and reduced antimicrobial activity when the drugs are co-administered with antacids or multi-vitamin preparations containing iron. The complexation of two model compounds, lomefloxacin and norflaxacin was studied using NMR. With aluminum ions, exchange between free and bound drug molecules was slow on the NMR timescale. Two complexes, proposed to have stoichiometries of 2:1 and 3:1 (drug:metal) based on peak widths and variable temperature studies, were observed. The crystal structure of lomefloxacin, which shows intermolecular self association previously reported to be crucial to the drug's mode of action, is also reported. Because the metal ion complexes could not be crystallized, the crystal structure of uncomplexed lomefloxacin together with the NMR data on the aluminum complexes were used in the molecular modelling of the lomefloxacin-aluminum complexes.
引用
收藏
页码:49 / 59
页数:11
相关论文
共 41 条
[1]   NALIDIXIC-ACID [J].
ACHARI, A ;
NEIDLE, S .
ACTA CRYSTALLOGRAPHICA SECTION B-STRUCTURAL SCIENCE, 1976, 32 (FEB15) :600-602
[2]  
[Anonymous], 1974, INT TABLES XRAY CRYS, VIV
[3]   THE STRUCTURE OF SILVER PEFLOXACIN, AN ANTIBIOTIC RELATED TO NALIDIXIC-ACID [J].
BAENZIGER, NC ;
FOX, CL ;
MODAK, SL .
ACTA CRYSTALLOGRAPHICA SECTION C-CRYSTAL STRUCTURE COMMUNICATIONS, 1986, 42 :1505-1509
[4]   THE COMPLEXATION OF TRANSITION SERIES METAL-IONS BY NALIDIXIC-ACID AND RELATED METHOXYQUINOLONES - ITS INFLUENCE ON PARTITION-COEFFICIENTS WITH REFERENCE TO ANTIBACTERIAL ACTIVITY [J].
BAILEY, AJG ;
COLE, A ;
GOODFIELD, J ;
MAY, PM ;
DREYFUSS, ME ;
MIDGLEY, JM ;
WILLIAMS, DR .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1984, 22 (2-3) :283-290
[5]   INFLUENCE OF URINARY PH ON THE PHARMACOKINETICS OF CINOXACIN IN HUMANS AND ON ANTIBACTERIAL ACTIVITY INVITRO [J].
BARBHAIYA, RH ;
GERBER, AU ;
CRAIG, WA ;
WELLING, PG .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1982, 21 (03) :472-480
[6]   METAL-COMPLEXES OF THE ANTIBIOTIC NALIDIXIC-ACID [J].
BEHRENS, NB ;
DIAZ, GM ;
GOODGAME, DML .
INORGANICA CHIMICA ACTA-BIOINORGANIC CHEMISTRY, 1986, 125 (01) :21-26
[8]   DECREASED CIPROFLOXACIN ABSORPTION WITH CONCOMITANT ADMINISTRATION OF FERROUS FUMARATE [J].
BROUWERS, JRBJ ;
VANDERKAM, HJ ;
SIJTSMA, J ;
PROOST, JH .
PHARMACEUTISCH WEEKBLAD-SCIENTIFIC EDITION, 1990, 12 (05) :182-183
[9]   THE ACIDITY OF NORFLOXACIN [J].
BUCKINGHAM, DA ;
CLARK, CR ;
NANGIA, A .
AUSTRALIAN JOURNAL OF CHEMISTRY, 1990, 43 (02) :301-309
[10]   NORFLOXACIN INTERACTION WITH ANTACIDS AND MINERALS [J].
CAMPBELL, NRC ;
KARA, M ;
HASINOFF, BB ;
HADDARA, WM ;
MCKAY, DW .
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1992, 33 (01) :115-116