Skip to main content

Advertisement

SpringerLink
Log in

Solid-state synthesis of isostructural tetrachlorometallate salts of amodiaquine: crystal structure of [CdCl4][C20H24ClN3O]

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

Tetrachlorometallate salts [AMDH2+][CoCl4]2− 1a and [AMDH2+][CdCl4]2− 2a (AMDH2+ = amodiaquine dication) were obtained by ball milling of amodiaquine with inorganic salts CoCl2·6H2O and CdCl2·6H2O, respectively, in the absence of solvent. Solution-based synthesis of [AMDH2+][CoCl4]2− 1b and [AMDH2+][CdCl4]2− 2b were also carried out by reaction of amodiaquine with the corresponding metal salts under reflux in methanol for 1 h. The analytical and spectroscopic data (IR, UV–Vis and NMR spectra) obtained for the compounds prepared via the two different routes are identical. The XPRD pattern of 1a closely matched the simulated pattern obtained from its reported single-crystal data. Single crystals of 2b suitable for X-ray structural analysis were obtained. The X-ray structure of 2b revealed an ionic compound with formula unit comprising of one protonated dicationic amodiaquine molecule and a tetrachlorocadmate(II) anion. The crystals are triclinic with space group P-1 and unit dimensions a = 9.3272(8) Å, b = 11.1418(9) Å, c = 12.482(10) Å, V = 1191.89 Å3, and Z = 2. The amodiaquine molecule is protonated both at the quinoline and quinuclidine nitrogen atom. Antimalarial efficacy of 1a on Plasmodium berghei-infected mice were investigated, and the results revealed an enhanced activity of the compound by significantly (p < 0.05) improving the suppression of parasitemia in established infection when compared with the controls.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Scheme 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Adams CJ, Haddow MF, Hughes RJ, Kurawa MA, Orphen AG (2010) Coordination chemistry of platinum and palladium in solid-state: synthesis of imidazole and pyrazole complexes. Dalton Trans 39:3714–3724

    Article  CAS  PubMed  Google Scholar 

  • Ajibade PA, Kolawole GA (2008) Synthesis, characterization and in vitro antiprotozoal studies of iron(III) complexes of some antimalarial drugs. J Coord Chem 61:3367–3374

    Article  CAS  Google Scholar 

  • Amin M, Iqbal MS, Hughes RW, Khan SA, Reynolds PA, Enne VI, Sajjad-ur-Rahman Mirza AS (2010) Mechanochemical synthesis and in vitro anti-Helicobacter pylori and uresase inhibitory activities of novel zinc(II)–famotidine complex. J Enzym Inhib Med Chem 25:383–390

    Article  CAS  Google Scholar 

  • Arancibia R, Dubar F, Pradines B, Forfar I, Dive D, Klahn AH, Biot C (2010) Synthesis and antimalarial activities of rhenium bioorganometallics based on the 4-aminoquinoline structure. Bioorg Med Chem 18:8085–8091

    Article  CAS  PubMed  Google Scholar 

  • Azumi R, Honda K, Goto M, Akimoto J, Oosawa Y, Tachibana H, Nakamura T, Tanaka M, Matsumoto M (1995) Bis(4-nitroanilinium) tetrachorocadmate. Acta Cryst C 51:2534–2537

    Article  Google Scholar 

  • Biot C, Delhaes L, Maciejewski LA, Mortuaire M, Camus D, Dive D, Brocard JS (2000) Synthesis of ferrocene mefloquine and quinine analog as potential antimalarial agents. Eur J Med Chem 35:707–714

    Article  CAS  PubMed  Google Scholar 

  • Biot C, Castro W, Botté CY, Navarro M (2012) The therapeutic potential of metal-based antimalarial agents: implications for the mechanism of action. Dalton Trans 41:6335–6349

    Article  CAS  PubMed  Google Scholar 

  • Braga D, Grepioni F, Maini L, Brescello R, Cotarca L (2008) Simple and qualitative mechanochemical preparation of the first zinc and copper complexes of the neuroleptic drug gabapentin. CrystEngComm 10:469–471

    Article  CAS  Google Scholar 

  • Casabianca LB, de Dios AC (2004) 13C NMR study of the self-association of chloroquine, amodiaquine, and quinine. J Phys Chem A 108:8505–8513

    Article  CAS  Google Scholar 

  • Chaabane I, Hlel F, Guidara K (2008) Synthesis, Infra-red, Raman, NMR and structural characterization by X-ray diffraction of [C12H17N2]2CdCl4 and [C6H10N2]CdCl3Cl10 compounds. PMC Phys B 11:1–19

    Google Scholar 

  • Dormale O, Blampain G, Agnaniet H, Nzadiyabi T, Lebibi J, Brocard J, Maciejewski L, Biot C, Georges AJ, Millet P (1998) In vitro antimalarial activity of a new organometallic analogue, Ferrocene-Chloroquine. Antimicrob Agent Chemother 42:540–544

    Google Scholar 

  • Hubel R, Polborn K, Beck W (1999) Metal complexes of biologically important ligands: Cinchona alkaloids as versatile ambivalent ligands-coordination of transition metals to the four potential donor sites of quinine. Eur J Inorg Chem 1999:471–482

    Article  Google Scholar 

  • Laurent F, Saivin S, Chretien P, Magnaval JF, Peyron F, Sqalli A, Tufenkji AE, Coulais Y, Baba H, Campistron G (1993) Pharmacokinetic and pharmacodynamic study of amodiaquine and its two metabolites after a single oral dose in human volunteers. Arzneim Forsch 43:612–616

    CAS  Google Scholar 

  • Naisbitt DJ, Ruscoe JE, Williams D, O’Neil PM, Pirmohamed M, Park BK (1997) Disposition of amodiaquine and related antimalarial agents in human neutrophils: implications for drug design. J Pharmacol Exp Ther 280:884–893

    CAS  PubMed  Google Scholar 

  • Navarro M, Castro W, Biot C (2012) Bioorganometallic compounds with antimalarial targets: inhibiting hemozoin formation. Organometallics 31:5715–5727

    Article  CAS  Google Scholar 

  • Neftek KA, Woodtly W, Schmid M (1986) Amodiaquine induced agranulocytosis and liver damage. Br Med J 292:721–723

    Article  Google Scholar 

  • Neve F, Francescangeli O, Crispini A (2002) Crystal architecture and mesophase structure of long-chain N-alkylpyridinium tetrachlorometallates. Inorg Chim Acta 338:51–58

    Article  CAS  Google Scholar 

  • Obaleye JA, Caira MR, Tella AC (2007) Synthesis and characterization of some zinc(II) polymeric complexes using quinine. J Chem Cryst 25:19–28

    Google Scholar 

  • Obaleye JA, Caira MR, Tella AC (2009) Synthesis, characterization and crystal structures of the tetrachlorocuprate and tetrabromocadmate salts of the antimalarial mefloquine. Struct Chem 20:859–868

    Article  CAS  Google Scholar 

  • Ogunlana OO, Ogunlana OE, Ademowo OG (2012) Antiplasmodial activity of quinine-zinc complex and chloroquine: a comparative in vitro assessment. Afr J Pharm Pharmacol 6:516–519

    Article  CAS  Google Scholar 

  • Oleksyn BJ, Stadnicka KM, Hodorowicz SA (1978) The crystal structure and absolute configuration of cinchoninium tetrachlorocadmate(II) dihydrate. Acta Cryst B 34:811–816

    Article  Google Scholar 

  • Pichon A, Lazuen-Garay A, James SL (2006) Solvent-free synthesis of microporous metal-organic framework. CrystEngComm 8:211–214

    Article  CAS  Google Scholar 

  • Sanchez-Delgado RA, Navarro M, Perez H, Urbina JA (1996) Toward a novel metal-based chemotherapy against tropical diseases.2. Synthesis and antimalarial activity in vitro and in vivo of new ruthenium- and rhodium-chloroquine complexes. J Med Chem 39:1095–1099

    Article  CAS  PubMed  Google Scholar 

  • Semeniuk A, Niedospial A, Kalinowska-Tluscik J, Nitek W, Oleksyn BJ (2008) Molecular geometry of antimalarial amodiaquine in different crystalline environments. J Mol Struct 875:32–41

    Article  CAS  Google Scholar 

  • Tacke R, Kornek T, Heinrich T, Burschka C, Penka M, Pülm M, Keim C, Mutschler E, Lambrecht G (2001) Syntheses and pharmacological characterization of achiral and chiral enantiopure C/Si/Ge-analogous derivatives of the muscarinic antagonist cycrimine: a study on C/Si/Ge bioisosterism. J Organomet Chem 640:140–165

    Article  CAS  Google Scholar 

  • Tella AC, Obaleye JA (2010) Synthesis of some 3d metal complexes of quinine and their toxicological studies. J Nepal Chem Soc 25:19–28

    Article  CAS  Google Scholar 

  • Tella AC, Eke UB, Isaac AY, Ojekanmi AO (2011) Mechanically-induced solvent-less synthesis of cobalt and nickel complexes of cimetidine drug. Orbital Electron J Chem 3:94–103

    CAS  Google Scholar 

  • Tella AC, Isaac AY, Adeniran RA (2012) Mechanochemical synthesis of 2,4-dinitrophenylhydrazine metal complexes. Int J Appl Chem 8:25–32

    Google Scholar 

  • Tella AC, Obaleye JA, Eke UB, Isaac AY, Ameen OM (2014) Solvent-free synthesis, X-ray studies and in vitro inhibitory activities of copper(II) complexes of non-steroidal anti-inflammatory drugs. Res Chem Intermed 40:1441–1457

    Article  CAS  Google Scholar 

  • Wasi N, Singh HB, Gajanana A, Raichowdhar AN (1987) Synthesis of metal complexes of antimalaria drugs and in vitro evaluation of their activity against plasmodium falcipraum. Inorg Chim Acta 135:133–137

    Article  CAS  Google Scholar 

  • Watkins WM, Sixsmith DG, Spencer HG, Boriga DA, Karjuki DM, Kipingor T, Koech DK (1984) Effectiveness of amodiaquine as a treatment for chloroquine resistant Plasmodium falciparum. Lancet 1:357–359

    Article  CAS  PubMed  Google Scholar 

  • Weselucha-Birczynska A, Dyek M, Paluszkiewicz C (1990) FT-IR spectra of water in cinchoninium tetrachlorocadmate(II) dihydrate and cinchoninium tetrachlorozincate(II) dihydrate complexes. J Mol Struct 219:73–76

    Article  CAS  Google Scholar 

  • WHO (2001) Antimalarial drug combination therapy. Report of a technical consultation Geneva Switzerland WHO/CDS/RBM 35

Download references

Acknowledgments

ACT is grateful to the Association of African Universities for the award of 2011 AAU–Staff Exchange Fellowship at University of Cape Town, South Africa. The authors are also grateful to Dr. Michael Worle from ETH, Zurich, for help with structure determination during the 2013 Zurich School of Crystallography, Institute of Organic Chemistry, University of Zurich.

Author information

Authors and Affiliations

  1. Department of Chemistry, University of Ilorin, P.M.B 1515, Ilorin, Nigeria

    Adedibu C. Tella & Samson O. Owalude

  2. Department of Chemistry, University of Uyo, Uyo, Nigeria

    Nzikahyel Simon

  3. Department of Biochemistry, University of Ilorin, P.M.B 1515, Ilorin, Nigeria

    Rotimi O. Arise

Authors
  1. Adedibu C. Tella
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Samson O. Owalude
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nzikahyel Simon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rotimi O. Arise
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Adedibu C. Tella.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 305 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tella, A.C., Owalude, S.O., Simon, N. et al. Solid-state synthesis of isostructural tetrachlorometallate salts of amodiaquine: crystal structure of [CdCl4][C20H24ClN3O]. Med Chem Res 24, 3949–3957 (2015). https://doi.org/10.1007/s00044-015-1435-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-015-1435-4

Keywords

Search

Navigation