title: Metal complexes of quinolone antibiotics and their applications: an update.
abstract: Quinolones are synthetic broad-spectrum antibiotics with good oral absorption and excellent bioavailability. Due to the chemical functions found on their nucleus (a carboxylic acid function at the 3-position, and in most cases a basic piperazinyl ring (or another N-heterocycle) at the 7-position, and a carbonyl oxygen atom at the 4-position) quinolones bind metal ions forming complexes in which they can act as bidentate, as unidentate and as bridging ligand, respectively. In the polymeric complexes in solid state, multiple modes of coordination are simultaneously possible. In strongly acidic conditions, quinolone molecules possessing a basic side nucleus are protonated and appear as cations in the ionic complexes. Interaction with metal ions has some important consequences for the solubility, pharmacokinetics and bioavailability of quinolones, and is also involved in the mechanism of action of these bactericidal agents. Many metal complexes with equal or enhanced antimicrobial activity compared to the parent quinolones were obtained. New strategies in the design of metal complexes of quinolones have led to compounds with anticancer activity. Analytical applications of complexation with metal ions were oriented toward two main directions: determination of quinolones based on complexation with metal ions or, reversely, determination of metal ions based on complexation with quinolones.
authors.affiliation: Department of General and Inorganic Chemistry, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia St, Bucharest 020956, Romania. uivarosi.valentina@umf.ro
authors.forename: Valentina
authors.initials: V
authors.lastname: Uivarosi
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D015363:Quinolones / Q000737:chemistry* / Q000494:pharmacology; D012995:Solubility
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D015363:Quinolones
references.citation: Nat Struct Mol Biol. 2010 Sep;17(9):1152-3
references.pmid: 20802486
references.citation: Bioinorg Chem Appl. 2009;:914105
references.pmid: 19657456
references.citation: Bioorg Med Chem Lett. 2007 Mar 1;17(5):1238-42
references.pmid: 17196389
references.citation: J Inorg Biochem. 2011 Jan;105(1):63-74
references.pmid: 21134604
references.citation: Clin Infect Dis. 2000 Aug;31 Suppl 2:S24-8
references.pmid: 10984324
references.citation: Pharmacotherapy. 1989;9(6):377-80
references.pmid: 2616352
references.citation: J Fluoresc. 2005 Sep;15(5):673-8
references.pmid: 16341784
references.citation: Spectrochim Acta A Mol Biomol Spectrosc. 2012 Oct;96:790-5
references.pmid: 22925903
references.citation: Microbiol Mol Biol Rev. 1997 Sep;61(3):377-92
references.pmid: 9293187
references.citation: Science. 1980 Feb 29;207(4434):953-60
references.pmid: 6243420
references.citation: Eur J Clin Microbiol. 1985 Jun;4(3):345
references.pmid: 3160584
references.citation: J Inorg Biochem. 2010 Aug;104(8):843-50
references.pmid: 20444502
references.citation: Int J Antimicrob Agents. 2000 Sep;16(1):5-15
references.pmid: 11185413
references.citation: Eur J Pharm Biopharm. 2005 Sep;61(1-2):87-93
references.pmid: 16005199
references.citation: J Pharm Sci. 1996 Aug;85(8):803-9
references.pmid: 8863267
references.citation: J Inorg Biochem. 2010 Apr;104(4):455-66
references.pmid: 20106531
references.citation: J Chemother. 2005 Apr;17(2):169-73
references.pmid: 15920901
references.citation: Acta Pharm. 2009 Sep;59(3):259-71
references.pmid: 19819823
references.citation: Antimicrob Agents Chemother. 2011 Dec;55(12):5421-9
references.pmid: 21876059
references.citation: J Inorg Biochem. 2007 May;101(5):831-40
references.pmid: 17383004
references.citation: Am Fam Physician. 2002 Feb 1;65(3):455-64
references.pmid: 11858629
references.citation: J Pharm Biomed Anal. 1996 Mar;14(5):561-9
references.pmid: 8738185
references.citation: Nucleic Acids Res. 2009 Feb;37(3):702-11
references.pmid: 19188255
references.citation: J Antimicrob Chemother. 2010 Aug;65(8):1551-61
references.pmid: 20542907
references.citation: Can J Infect Dis. 1999 May;10(3):207-38
references.pmid: 22346384
references.citation: J Inorg Biochem. 1997 Jun;66(4):241-5
references.pmid: 9161011
references.citation: J Pharm Anal. 2011 Feb;1(1):46-50
references.pmid: 29403681
references.citation: Bioorg Med Chem Lett. 2011 Mar 15;21(6):1802-6
references.pmid: 21316236
references.citation: J Pharm Biomed Anal. 1998 Dec;18(4-5):565-71
references.pmid: 9919956
references.citation: Acta Pharm Hung. 1993 May;63(3):105-14
references.pmid: 8362651
references.citation: Br J Cancer. 2002 Feb 1;86(3):443-8
references.pmid: 11875713
references.citation: In Vivo. 2005 Jan-Feb;19(1):269-76
references.pmid: 15796186
references.citation: Chem Rev. 2005 Feb;105(2):559-92
references.pmid: 15700957
references.citation: Analyst. 1992 Sep;117(9):1523-6
references.pmid: 1443643
references.citation: Eur J Med Chem. 2012 Sep;55:67-73
references.pmid: 22835721
references.citation: Eur J Med Chem. 2012 Apr;50:149-53
references.pmid: 22330206
references.citation: Pharm Acta Helv. 2000 Apr;74(4):371-7
references.pmid: 10812936
references.citation: J Pharm Pharm Sci. 2012;15(1):52-72
references.pmid: 22365088
references.citation: Spectrochim Acta A Mol Biomol Spectrosc. 2011 Nov;82(1):8-19
references.pmid: 21855402
references.citation: J Fluoresc. 2004 Nov;14(6):705-10
references.pmid: 15649022
references.citation: J Antimicrob Chemother. 1997 May;39(5):639-41
references.pmid: 9184364
references.citation: Analyst. 1989 May;114(5):627-30
references.pmid: 2757232
references.citation: Int J Pharm. 2007 Mar 6;332(1-2):24-30
references.pmid: 17174046
references.citation: J Pharm Sci. 1990 Nov;79(11):1023-8
references.pmid: 1963448
references.citation: J Inorg Biochem. 2010 Jul;104(7):740-9
references.pmid: 20403640
references.citation: J Inorg Biochem. 2008 Sep;102(9):1798-811
references.pmid: 18621421
references.citation: J Inorg Biochem. 2002 Sep 30;92(1):65-74
references.pmid: 12230989
references.citation: J Antimicrob Chemother. 1992 Oct;30(4):409-14
references.pmid: 1337067
references.citation: J Clin Biochem Nutr. 2009 Mar;44(2):119-24
references.pmid: 19308265
references.citation: Pharmazie. 1999 Jan;54(1):73-4
references.pmid: 9987802
references.citation: Antimicrob Agents Chemother. 1989 Nov;33(11):1841-4
references.pmid: 2610494
references.citation: Analyst. 1997 Jul;122(7):705-8
references.pmid: 9330040
references.citation: Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9671-5
references.pmid: 1409681
references.citation: Br J Clin Pharmacol. 1991 Mar;31(3):257-61
references.pmid: 2054264
references.citation: Environ Pollut. 2012 Dec;171:168-73
references.pmid: 22922456
references.citation: Bioorg Med Chem Lett. 2006 Jul 15;16(14):3864-7
references.pmid: 16697195
references.citation: J Inorg Biochem. 2006 Oct;100(10):1705-13
references.pmid: 16876251
references.citation: J Inorg Biochem. 2012 Aug;113:55-65
references.pmid: 22694822
references.citation: J Inorg Biochem. 2006 Nov;100(11):1755-63
references.pmid: 16934331
references.citation: J Fluoresc. 2006 Nov;16(6):831-7
references.pmid: 16983510
references.citation: Spectrochim Acta A Mol Biomol Spectrosc. 2008 Apr;69(4):1130-5
references.pmid: 17660000
references.citation: Talanta. 2007 Feb 15;71(2):816-21
references.pmid: 19071379
references.citation: J Inorg Biochem. 1998 Mar;69(4):231-9
references.pmid: 9654749
references.citation: Nucleic Acids Res. 2013 Apr;41(8):4628-39
references.pmid: 23460203
references.citation: Organometallics. 2011 May 9;30(9):2506-2512
references.pmid: 21552495
references.citation: Anal Sci. 2009 Jan;25(1):125-8
references.pmid: 19139586
references.citation: Met Based Drugs. 2000;7(2):101-4
references.pmid: 18475931
references.citation: Therap Adv Gastroenterol. 2011 Mar;4(2):103-14
references.pmid: 21694812
references.citation: Antimicrob Agents Chemother. 1994 Dec;38(12):2810-6
references.pmid: 7695267
references.citation: J Inorg Biochem. 2003 Jun 1;95(2-3):199-207
references.pmid: 12763665
references.citation: J Pharm Biomed Anal. 2012 Jul;66:50-7
references.pmid: 22464555
references.citation: J Inorg Biochem. 2010 Feb;104(2):161-70
references.pmid: 19939458
references.citation: Rev Infect Dis. 1989 Jul-Aug;11 Suppl 5:S1083-90
references.pmid: 2570456
references.citation: Spectrochim Acta A Mol Biomol Spectrosc. 2011 Dec 15;84(1):99-110
references.pmid: 21968206
references.citation: J Inorg Biochem. 2012 Dec;117:35-47
references.pmid: 23078773
references.citation: Chem Rev. 1998 Feb 5;98(1):327-358
references.pmid: 11851509
references.citation: Spectrochim Acta A Mol Biomol Spectrosc. 2008 Apr;69(4):1188-94
references.pmid: 17689288
references.citation: Met Based Drugs. 2000;7(6):301-11
references.pmid: 18475962
references.citation: Clin Infect Dis. 2001 Sep 15;33 Suppl 3:S180-6
references.pmid: 11524717
references.citation: Acta Crystallogr Sect E Struct Rep Online. 2008 Jan 09;64(Pt 2):m302
references.pmid: 21201277
references.citation: J Inorg Biochem. 2009 Jun;103(6):898-905
references.pmid: 19395041
references.citation: Dalton Trans. 2011 Oct 7;40(37):9461-73
references.pmid: 21853189
references.citation: J Fluoresc. 2011 Jan;21(1):113-8
references.pmid: 20602253
references.citation: Surv Ophthalmol. 2004 Mar;49 Suppl 2:S73-8
references.pmid: 15028482
references.citation: Bioorg Med Chem. 1998 Sep;6(9):1555-61
references.pmid: 9801827
references.citation: Spectrochim Acta A Mol Biomol Spectrosc. 2008 Jul;70(2):332-6
references.pmid: 17954035
references.citation: J Inorg Biochem. 1996 Apr;62(1):1-16
references.pmid: 8936419
references.citation: J Inorg Biochem. 1995 Sep;59(4):801-10
references.pmid: 7595467
references.citation: Int J Antimicrob Agents. 2003 May;21(5):446-51
references.pmid: 12727078
references.citation: J Fluoresc. 2011 Sep;21(5):1933-40
references.pmid: 21573968
references.citation: Int J Pharm. 2009 Apr 17;371(1-2):106-13
references.pmid: 19150493
references.citation: Curr Med Chem Anticancer Agents. 2003 Nov;3(6):439-50
references.pmid: 14529452
references.citation: Respir Med. 2009 Dec;103(12):1777-90
references.pmid: 19660927
references.citation: J AOAC Int. 2001 Mar-Apr;84(2):368-75
references.pmid: 11324600
references.citation: J Inorg Biochem. 2007 Apr;101(4):644-8
references.pmid: 17275912
references.citation: Bioorg Med Chem Lett. 2008 Jul 15;18(14):4033-7
references.pmid: 18579377
references.citation: Eur J Med Chem. 2009 Oct;44(10):4107-11
references.pmid: 19482387
references.citation: J Inorg Biochem. 1995 Oct;60(1):61-7
references.pmid: 7595471
references.citation: Spectrochim Acta A Mol Biomol Spectrosc. 2007 Dec 31;68(5):1393-405
references.pmid: 17467332
references.citation: J Inorg Biochem. 2006 Aug;100(8):1378-88
references.pmid: 16740311
references.citation: J Inorg Biochem. 2005 Mar;99(3):677-89
references.pmid: 15708788
references.citation: Lancet. 2011 Mar 12;377(9769):905-13
references.pmid: 21345487
references.citation: J Pharm Biomed Anal. 1998 Aug;17(4-5):829-40
references.pmid: 9682168
references.citation: Talanta. 1996 Apr;43(4):559-68
references.pmid: 18966519
references.citation: J Inorg Biochem. 2001 Apr;84(3-4):163-70
references.pmid: 11374578
references.citation: Talanta. 2010 Oct 15;82(5):1858-63
references.pmid: 20875588
references.citation: J Fluoresc. 2008 May-Jul;18(3-4):701-6
references.pmid: 18293067
references.citation: Biochim Biophys Acta. 1998 Oct 1;1400(1-3):45-61
references.pmid: 9748496
references.citation: Pharm Res. 1997 Mar;14(3):366-70
references.pmid: 9098883
references.citation: Pharmazie. 1988 Jun;43(6):444-7
references.pmid: 2850589
references.citation: J Inorg Biochem. 2003 Aug 1;96(2-3):407-15
references.pmid: 12888277
references.citation: J Inorg Biochem. 2006 Nov;100(11):1764-73
references.pmid: 16904184
references.citation: Dalton Trans. 2013 May 14;42(18):6252-76
references.pmid: 23529676
references.citation: Clin Res Hepatol Gastroenterol. 2013 Nov;37(5):527-9
references.pmid: 23312494
references.citation: J Pharm Biomed Anal. 2010 Nov 2;53(3):655-9
references.pmid: 20643295
references.citation: J Inorg Biochem. 1998 Aug;71(1-2):53-60
references.pmid: 9755492
references.citation: J Inorg Biochem. 1997 May 1;66(2):77-82
references.pmid: 9112758
references.citation: J Inorg Biochem. 2005 Feb;99(2):432-42
references.pmid: 15621275
references.citation: J Pharm Biomed Anal. 2005 Jul 1;38(3):528-31
references.pmid: 15925255
references.citation: Am Fam Physician. 2000 May 1;61(9):2741-8
references.pmid: 10821154
references.citation: Spectrochim Acta A Mol Biomol Spectrosc. 2010 Feb;75(2):520-4
references.pmid: 20022801
references.citation: Inorg Chem. 2010 Dec 6;49(23):10750-2
references.pmid: 20973588
references.citation: J Mol Biol. 2005 Nov 11;353(5):1152-60
references.pmid: 16223508
references.citation: J Pharm Sci. 2002 Nov;91(11):2416-23
references.pmid: 12379927