Physico-chemical, Biological properties, and Applications of Quinone, its Derivatives – A review

 

Shrikaant Kulkarni

Vishwakarma Institute of Technology, Pune, India

*Corresponding Author E-mail: srkulkarni21@gmail.com

Quinones are found to be a class of cyclic organic compounds containing a six-membered unsaturated ring to which two oxygen atoms are bonded as keto (carnonyl) groups. In nature, quinone plays a very vital role in many electrochemical reactions in energy transduction and storage applications. These processes involve respiration and photosynthesis. For example, fast electron transfer accompanied by proton-coupling between primary and secondary quinones in green plants induces the rapid charge separation of chlorophyll molecules, achieving photosynthesis with close to unity quantum yield. In addition, quinone-rich polymers such as eumelanin and polydopamine exhibit distinct optical and electrical properties attributed to their chemically disordered structures. Understanding the unique features of quinone and its derivatives can provide solutions to the design and development of bio-directed systems in the frontier areas like energy harvesting and conversion. This paper reviews quinone and its derivatives physic-chemical and biological properties like redox, electrical, optical, and metal chelating/reducing, medicinal, microbicidal, anticancer etc. to determine these materials' applications in energy-harvesting and -storage systems, such as artificial photosynthetic platforms, rechargeable batteries, pseudocapacitors, phototransistors, plasmonic light harvesting platforms, and dye-sensitized solar cells, sensors, drug delivery etc.

 

 

 

INTRODUCTION:

It is very well known that o-quinones complexed with transition and metals other than transition can exist in the form of either or neutral, radical anion (o-semiquinone) or dianion (catecholate) ligands^1,2,3. Unique properties of such complex compounds to bring about intramolecular redox transformations (tautomerism) and presence in the semi-quinolates unpaired electrons, which allow EPR spectroscopy and magnetic measurements to be used for their thorough study, make these candidates unique for investigation of the nature of metal ligand interaction^4.5.6.

 

The complexes with o-iminoquinones, which are closest electron analogues to o-quinones, are comparatively studied to a lesser degree although these ligands ligate as neutral, radical anion (iminosemiquinolate) or dianion (amidophenolate) O,N-chelate ligands. Comprehensive literature review devoted to 4,6-di-tertbutyl-N-aryl(alkyl)-o-iminobenzoquinonato complexes with transition metals has been reported in the recent study⁷. In this review and some other research papers one can see the synthesis and characterization of homoleptic and heterolepticiminobenzoquinolates of Zr, V, Cr, Mn⁸, Re⁹, Fe, Ru¹⁰, Os, Co, Ir, Ni, Pd, Pt, Cu, Ga, Tl, Ge and Sn. Phenanthreno-iminoquinone complex is meant for Ni in preference¹¹. Oxidation states of metal and ligand in these compounds depend on ionization energy of the metal and the nature of ligands in particular in heteroleptic complexes. A solitary example of rare earth metal iminoquinolates is the complexes of Sc(OTf)₃(TTQ)where TTQ (tryptophan tryptophylquinone derivatives) are cofactor of quinoprotein methylamine and aromatic amine¹². The complexes concerned have not been separated from the reaction mixtures but were characterized with the help of analytical tools like spectroscopy and used in situ as catalysts for oxidation of benzylamine to N-benzylidenebenzylamine. At the same time, the o-iminoquinolate complexes of 3 group metals and especially their phenanthren-o-iminoquinone analogues, which is known so far only for Ni¹¹, are of special interest as potential materials for optoelectronic devices. Similarity of N,O-Ln chelate fragments and conjugated p-electron system in the phenanthreno-iminoquinolates to those in the known lanthanide based electroluminophores¹³ forms the background to use these compounds as excellent luminescent materials.

 

Properties:

The paper presented here give us hope for the exploration of this field of chemistry of quinones and their derivatives in the future. E.g. 8- hydroyquinoline (HQ) proved to be a valuable scaffold for many biologically active compounds and several marketed drugs. The search of new 8-hydroyquinoline derivatives or delivery systems, to overcome the toxicity of HQs, keeping their pharmacological properties intact is underway. The presence of metal binding ability of the synthesized ligands seems to be essential to exhibit vital biological properties such as antibacterial, antioxidant and antiaggregant. The introduction of other groups such as NO₂ or COOH bestows the ability to interact with  selective enzymes whereas the conjugation with bioactive molecules or the building of hybrid systems makes these systems suitable for multifactorial diseases. The initial results of these studies are encouraging, indicating the great potential of HQs, HQ-like compounds and HQ-loaded systems in disease challenge^14,15,16.

 

HQ has shown interesting properties as fungicide, bactericide and antiproliferative agent. Naphthoquinones are compounds present in different families of plants; their molecular structures endow them with redox properties, which confer activity in various biological oxidative processes. The microbicidal activity of these naphthoquinones had been previously described by the group of Dr. Gonçalves de Lima in Recife (Pernambuco, Brazil).

 

Applications:

Qunones and their derivatives on complexing with either transition metals or lanthanides find widespread applications in a broad spectrum of applications. e.g.8-hydroxyquinolines (oxines, 8-quinolinols, HQs) and their derivatives which considered as a subclass of quinolines with a large play a variety of biological functions. Since historical times, HQ has been used as a fungicide in agriculture and a preservative in the textile, wood, and paper industries¹⁷. HQ and its derivatives are bidentate (functionality) ligands that bind metal ions through the oxygen and nitrogen atoms in preference to copper(II) and zinc(II) and possess excellent metal recognition properties, as a result, HQs are widely used for analytical, separation purposes and metal chelation^18,19,20.

 

HQ has emerged as a privileged lead candidate for new drug candidates that have been widely ored for their biological functins such as neuroprotection, anticancer, anti-HIV, antifungal effects. HQ has exhibited quite interesting properties as fungicide, bactericide and antiproliferative agent. The mode of action or the mechanism of HQ has been studied extensively by Albert and collaborators who showed that a metal is necessary for anti-bacterial activity^21,22,23. The nature of interaction with metal ions is crucial for its antiproliferative activity. Upon the complexation with copper or iron salts or cellular copper, HQ stifles proliferation of cancer cells in vitro and tumor growth in vivo. Copper/iron binding and transportation into cells are prerequisites for its cancer cell growth-inhibitory activities^21,22. More recently, HQ use has been proposed in conjunction with the incumbent cancer drugs like paclitaxel. As HQ is a cancer stem cell active compound, the combination with paclitaxel betters the therapeutic effect compared to either HQ or paclitaxel in isolation in both MCF7 and MDA-MB-435 xenograft models^23,24. However, so far very little information is available on human safety of HQ.

 

Another example is Ortho-quinone methides which are important synthetic intermediates and widely implicated in biological processes. Additionally, applications of these intermediates as partners in asymmetric synthesis and Pd-catalyzed formation of ortho-quinone methides and the trapping of intermediates with diverse nucleophiles have come to the fore.

 

This paper at first discuss some chemical-physical and biological properties of some representative quinone derivatives and applications on complexing with metals. This review outlines the progress in the field of these complex compounds, Q and HQ-loaded nanoparticle systems, with a specific focus on the biological activity of these systems. These properties are important to rationalize some therapeutic and toxic mechanisms. Quinones and the synthetic alternative routes to heterocycles may be considered promising candidates for medicinal chemistry studies in other fields of antimicrobial chemotherapy^22,23,24.

 

CONCLUSION:

This article reviews traditional medicinal chemistry, medicinal inorganic chemistry and nanomedicine of Qs and HQ-like compounds and the mechanism of their action. Just recently HQ and some derivatives have been proposed as building blocks or better lead compounds to obtain new drugs to treat a broad spectrum of pathologies related to metal dyshomeostasis, oxidative stress, aberrant protein-protein or metal-protein interactions. In this paper we have analyzed HQ, its derivatives and new approaches for the delivery of HQs through nanoparticles. To exploit fully the potential of HQs, it is absolutely essential to understand what happens to the HQ molecule, HQ complex or HQ-loaded nanoparticle system, once it enters the body. The study of pharmacological and toxicological properties of novel Q’s and HQs and thereby its interaction with biological target or essential metal ions is very much.

 

Quinone and their derivatives play an important role as ligands which on complexations will find plethora of applications by virtue of the range of properties possessed by them.

 

REFERENCES:

1.     C.G. Pierpont, Coord. Chem. Rev. 216e217 (2001) 99e125.

2.     C.G. Pierpont, Coord. Chem. Rev. 219e221 (2001) 415e433.

3.     A.S. Attia, B.J. Conklin, C.W. Lange, C.G. Pierpont, Inorg. Chem. 35 (1996) 1033e1038.

4.     D.N. Hendrickson, C.G. Pierpont, Top. Curr. Chem. 234 (2004) 63e95.

5.     O. Sato, J. Tao, Y.-Z. Zhang, Angew. Chem. Int. Ed. 46 (2007) 2152e2187.

6.     E. Evangelio, D. Ruiz-Molina, Eur. J. Inorg. Chem. (2005) 2957e2971.

7.     A.I. Poddel’sky, V.K. Cherkasov, G.A. Abakumov, Coord. Chem. Rev. 253 (2009) 291e324 and references cited therein.

8.     H. Chun, P. Chaudhuri, T. Weyhermüller, K. Wieghardt, Inorg. Chem. 41 (2002) 790e795.

9.     G.A. Abakumov, A.I. Poddel’sky, M.P. Bubnov, G.K. Fukin, L.G. Abakumova, V.N. Ikorskii, V.K. Cherkasov, Inorg. Chim. Acta 358 (2005) 3829e3840.

10.   S. Bhattacharya, P. Gupta, F. Basuli, C.G. Pierpont, Inorg. Chem. 41 (2002) 5810e5816.

11.   G.A. Abakumov, V.K. Cherkasov, N.O. Druzhkov, Yu. A. Kurskii, G.K. Fukin, L.G. Abakumova, T.N. Kocherova, Synth. Commun. 36 (2006) 3241e3247.

12.   S. Itoh, M. Taniguchi, N. Takada, S. Nagatomo, T. Kitagawa, S. Fukuzumi, J. Am. Chem. Soc. 122 (2000) 12087e12097.

13.   (a) M.A. Katkova, A.G. Vitukhnovskii, M.N. Bochkarev, Russ. Chem. Rev. 74 (2005) 1089e1109; (b) M.N. Bochkarev, M.A. Katkova, Rare earth metals and their complexes in organic light emitting diodes. in: N.P. Chen (Ed.), Handbook of Light Emitting and Schottky Diode Research. Nova Science Publishers, New York, 2009, pp. 1e65.

14.   Shrikaant Kulkarni et al, A Green facile synthesis and characterization of 2,3-dihydroxy-1,4-napthoquinone, Journal of Chemical, Biological and Physical Sciences, August 2015 – October 2015, Vol. 5, No. 4; 3645-3651

15.   Shrikaant Kulkarni et al, Synthesis of Complexes of Lanthanide ions with 2,2’:6’, 2”-terpyridine Ligands for Luminescence Properties, International Journal of Chemistry and Applications, Vol. 9, No.1, pp. 9-14, 2017.

16.   Shrikaant Kulkarni et al, Synthesis, Characterization and Physio-chemical and Antimicrobial Investigation of Selected Lanthanide Ions with Schiff Base, Journal of Chemistry and Chemical Sciences, Vol.7(3), 272-279, March 2017.

17.   S. S. Block, Application and use of fungicides as industrial preservatives in Fungicides: An Advanced Treatise, Academic Press, New York (2012) 379-416.

18.   A. Goswami, A. K. Singh, B. Venkataramani, 8-Hydroxyquinoline anchored to silica gel via new moderate size linker: synthesis and applications as a metal ion collector for their flame atomic absorption spectrometric determination, Talanta 60 (2003) 1141-1154.

19.   A. Albert, S. D. Rubbo, R. J. Goldacre, B. G. Balfour, The influence of chemical constitution on antibacterial activity. Part III: A study of 8-hydroxyquinoline (oxine) and related compounds, Br. J. Exp. Pathol. 28 (1947) 69-87.

20.   A. Albert, M. I. Gibson, S. D. Rubbo, The influence of chemical constitution on anti-bacterial activity. Part VI: the bactericidal action of 8-hydroxyquinoline (oxine), Br. J. Exp. Pathol. 34 (1953) 119-130.

21.   A. Albert, A. Hampton, F. R. Selbie, R. D. Simon, The Influence of Chemical Constitution on Antibacterial Activity. Part VII: the Site of Action of 8-Hydroxy-Quinoline (Oxine), Br. J. Exp. Pathol. 35 (1954) 75-84.

22.   S. Zhai, L. Yang, Q. C. Cui, Y. Sun, Q. P. Dou, B. Yan, Tumor cellular proteasome inhibition and growth suppression by 8-hydroxyquinoline and clioquinol requires their capabilities to bind copper and transport copper into cells, J. Biol. Inorg. Chem. 15 (2010) 259-269.

23.   P. Leanderson, C. Tagesson, Iron bound to the lipophilic iron chelator, 8-hydroxyquinoline, causes DNA strand breakage in cultured lung cells, Carcinogenesis, 17 (1996) 545-550.

24.   Zhou, H. Zhang, P. Gu, J. B. Margolick, D. Yin, Y. Zhang, Cancer stem/progenitor cell active compound 8-quinolinol in combination with paclitaxel achieves an improved cure of breast cancer in the mouse model, Breast Cancer Res. Treat. 115 (2009) 269-277.

 

 

 

Received on 14.10.2017         Modified on 12.12.2017

Accepted on 20.12.2017         © AJRC All right reserved