Ionic Liquid-Like Pharmaceutical Ingredients and Applications of Ionic Liquids in Medicinal Chemistry: Development, Status and Prospects

Jie       Tang; Hang       Song; Xueting       Feng; Alula       Yohannes; Shun       Yao
doi:10.2174/0929867325666180605123436
Abstract

Background: As a new kind of green media and bioactive compounds with special structure, Ionic Liquids (ILs) are attracting much attention and applied widely in many fields. However, their roles and potential have not been fully recognized by many researchers of medicinal chemistry. Because of obvious differences from other traditional drugs and reagents, their uses and performance together with advantages and disadvantages need to be explored and reviewed in detail.
Methods: For a systematic and explicit description of the relationship between ILs and medicinal chemistry, all of the contents were elucidated and summarized in a series of independent parts. In each part, it started from the research background or a conceptual framework and then specific examples were introduced to illustrate the theme. Finally, the important conclusions were drawn and its future was outlooked after the discussion about related key problems appearing in each mentioned research. Meanwhile, methodologies such as empirical analysis, comparison and induction were applied in different sections to exposit our subject.
Results: The whole review was composed of five parts, and 148 papers were cited in total. Related basic information of ionic liquids was provided on the basis of representative references, including their concepts and important characters. Then 82 papers outlined ionic liquid-like active pharmaceutical ingredients, which unfolded with their major biological activities (antimicrobial activity, antibiofilm activity, antitumor activity, anticholinesterase activity and so on). Applications of ionic liquids in the synthesis of drugs and pharmaceutical intermediates were elaborated in 92 papers to illustrate the important roles of ILs and their extraordinary properties in this field. Moreover, new technologies (such as immobilization of IL, microwave reaction, solventfree synthesis, microreactor, etc) were introduced for further innovation. Finally, 26 papers were included to expound the status of the IL-assisted derivatization of various natural lead compounds.
Conclusion: This review placed emphasis on chemical structures of ILs and their structureactivity relationships in a specific manner, leading to meaningful and valuable related information to some related fields and thus promotes further development and application of various ILs for medicinal chemistry. The deep exploration for key scientific problems is the driving force to propel their theoretical breakthrough and industrial production.
Keywords: Ionic liquids, medicinal chemistry, pharmaceutical ingredients, activities, synthesis, green media, industrial production.
« Previous Next »
[1] 
Wilkes, J.S. A short history of ionic liquids–From molten salts to neoteric. Green Chem.,  2002, 4, 73-80.
[http://dx.doi.org/10.1039/b110838g] 
[2] 
Weingärtner, H. Understanding ionic liquids at the molecular level: facts, problems, and controversies. Angew. Chem. Int. Ed. Engl.,  2008, 47(4), 654-670.
[http://dx.doi.org/10.1002/anie.200604951] [PMID:  17994652] 
[3] 
Seddon, K.R. Ionic liquids: a taste of the future. Nat. Mater.,  2003, 2(6), 363-365.
[http://dx.doi.org/10.1038/nmat907] [PMID:  12776100] 
[4] 
Dupont, J.; de Souza, R.F.; Suarez, P.A. Ionic liquid (molten salt) phase organometallic catalysis. Chem. Rev.,  2002, 102(10), 3667-3692.
[http://dx.doi.org/10.1021/cr010338r] [PMID:  12371898] 
[5] 
Rogers, R.D.; Seddon, K.R. Chemistry. Ionic liquids--solvents of the future? Science,  2003, 302(5646), 792-793.
[http://dx.doi.org/10.1126/science.1090313] [PMID:  14593156] 
[6] 
Welton, T. Room-temperature ionic liquids: solvents for synthesis and catalysis. Chem. Rev.,  1999, 99(8), 2071-2084.
[http://dx.doi.org/10.1021/cr980032t] [PMID:  11849019] 
[7] 
Hiroyuki, O. Functional design of ionic liquids. Chem. Soc. Jpn.,  2006, 79, 1665-1680.
[http://dx.doi.org/10.1246/bcsj.79.1665] 
[8] 
Angell, C.A.; Ansari, Y.; Zhao, Z. Ionic liquids: past, present and future. Faraday Discuss.,  2012, 154, 9-27.
[http://dx.doi.org/10.1039/C1FD00112D] [PMID:  22455011] 
[9] 
Sekhon, B.S. Ionic liquids: pharmaceutical and biotechnological applications. Asian J. Pharm. Biol. Res.,  2011, 1, 395-411.
[10] 
Smiglak, M.; Pringle, J.M.; Lu, X.; Han, L.; Zhang, S.; Gao, H.; MacFarlane, D.R.; Rogers, R.D. Ionic liquids for energy, materials, and medicine. Chem. Commun. (Camb.),  2014, 50(66), 9228-9250.
[http://dx.doi.org/10.1039/C4CC02021A] [PMID:  24830849] 
[11] 
Syguda, A.; Marcinkowska, K.; Materna, K. Pyrrolidinium herbicidal ionic liquids. Rsc Adv.,  2016, 6, 63136-63142.
[http://dx.doi.org/10.1039/C6RA12157H] 
[12] 
Simmons, K.J.; Chopra, I.; Fishwick, C.W. Structure-based discovery of antibacterial drugs. Nat. Rev. Microbiol.,  2010, 8(7), 501-510.
[http://dx.doi.org/10.1038/nrmicro2349] [PMID:  20551974] 
[13] 
Mital, A. Synthetic nitroimidazoles: Biological activities and mutagenicity relationships. Sci. Pharm.,  2009, 77, 497-520.
[http://dx.doi.org/10.3797/scipharm.0907-14] 
[14] 
Liu, L.X.; Weller, P.F. Antiparasitic drugs. N. Engl. J. Med.,  1996, 334(18), 1178-1184.
[http://dx.doi.org/10.1056/NEJM199605023341808] [PMID:  8602186] 
[15] 
Kulik, A.; Białecka, W.; Podolska, M.; Kwiatkowska-Puchniarz, B.; Mazurek, A. HPLC method for identification and quantification of benzimidazole derivatives in antiparasitic drugs. Acta Pol. Pharm.,  2011, 68(6), 823-829.
[PMID:  22125945] 
[16] 
Davis, J.H.; Kerri, J.F.; Travis, M. Novel organic ionic liquids (OILs) incorporating cations derived from the antifungal drug miconazole. Tetrahedron Lett.,  1998, 39, 8955-8958.
[http://dx.doi.org/10.1016/S0040-4039(98)02070-X] 
[17] 
Hough, W.L.; Rogers, R.D. Ionic liquids then and now: from solvents to materials to active pharmaceutical ingredients. Chem. Soc. Jpn.,  2007, 80, 2262-2269.
[http://dx.doi.org/10.1246/bcsj.80.2262] 
[18] 
Ranke, J.; Stolte, S.; Störmann, R.; Arning, J.; Jastorff, B. Design of sustainable chemical products--the example of ionic liquids. Chem. Rev.,  2007, 107(6), 2183-2206.
[http://dx.doi.org/10.1021/cr050942s] [PMID:  17564479] 
[19] 
Messali, M. Eco-friendly synthesis of a new class of pyridinium-based ionic liquids with attractive antimicrobial activity. Molecules,  2015, 20(8), 14936-14949.
[http://dx.doi.org/10.3390/molecules200814936] [PMID:  26287148] 
[20] 
Docherty, K.M. Toxicity and antimicrobial activity of imidazolium and pyridinium ionic liquids. Green Chem.,  2005, 7, 185-189.
[http://dx.doi.org/10.1039/b419172b] 
[21] 
Foksowicz-Flaczyk, J.; Walentowska, J. Antifungal activity of ionic liquid applied to linen fabric. Int. Biodeter. Biodegr.,  2013, 84, 412-415.
[http://dx.doi.org/10.1016/j.ibiod.2012.05.025] 
[22] 
Garcia, M.T.; Ribosa, I.; Perez, L.; Manresa, A.; Comelles, F. Aggregation behavior and antimicrobial activity of ester-functionalized imidazolium- and pyridinium-based ionic liquids in aqueous solution. Langmuir,  2013, 29(8), 2536-2545.
[http://dx.doi.org/10.1021/la304752e] [PMID:  23360222] 
[23] 
Foksowicz-Flaczyk, J.; Walentowska, J. Eco-friendly antimicrobial finishing of natural fibres. Mol. Cryst. Liq. Crys.,  2008, 484, 573-578.
[http://dx.doi.org/10.1080/15421400801904526] 
[24] 
Carson, L.; Chau, P.K.W.; Earle, M.J.; Gilea, M.A.; Gilmore, B.F.; Gorman, S.P.; McCann, M.T.; Seddon, K.R. Antibiofilm activities of 1-alkyl-3-methylimidazolium chloride ionic liquids. Green Chem.,  2009, 11, 492-497.
[http://dx.doi.org/10.1039/b821842k] 
[25] 
Łuczak, J.; Jungnickel, C.; Łacka, I.; Stolte, S.; Hupka, J. Antimicrobial and surface activity of 1-alkyl-3-methylimidazolium derivatives. Green Chem.,  2010, 12, 593-601.
[http://dx.doi.org/10.1039/b921805j] 
[26] 
Pernak, J.; Sobaszkiewicz, K.; Mirska, I. Anti-microbial activities of ionic liquids. Green Chem.,  2003, 5, 52-56.
[http://dx.doi.org/10.1039/b207543c] 
[27] 
Paweł, B.; Małgorzata, M.K.; Dominika, B.; Monika, W.; Jan, P. Synthesis and antimicrobial activity of imidazolium and triazolium chiral ionic liquids. Eur. J. Org. Chem.,  2013, 4, 712-720.
[28] 
Iwai, N.; Nakayama, K.; Kitazume, T. Antibacterial activities of imidazolium, pyrrolidinium and piperidinium salts. Bioorg. Med. Chem. Lett.,  2011, 21(6), 1728-1730.
[http://dx.doi.org/10.1016/j.bmcl.2011.01.081] [PMID:  21324694] 
[29] 
Cornellas, A.; Perez, L.; Comelles, F.; Ribosa, I.; Manresa, A.; Garcia, M.T. Self-aggregation and antimicrobial activity of imidazolium and pyridinium based ionic liquids in aqueous solution. J. Colloid Interface Sci.,  2011, 355(1), 164-171.
[http://dx.doi.org/10.1016/j.jcis.2010.11.063] [PMID:  21186035] 
[30] 
Alberto, E.E.; Rossato, L.L.; Alves, S.H.; Alves, D.; Braga, A.L. Imidazolium ionic liquids containing selenium: synthesis and antimicrobial activity. Org. Biomol. Chem.,  2011, 9(4), 1001-1003.
[http://dx.doi.org/10.1039/C0OB01010C] [PMID:  21157603] 
[31] 
Brendan, F.G.; Gavin, P.A.; Gabor, B.; Martyn, J.E.; Manuela, A.G.; Sean, P.G.; Andrew, F.L.; Martin, M.; Kenneth, R.S. Enhanced antimicrobial activities of 1-alkyl-3-methyl imidazolium ionic liquids based on silver or copper containing anions. New J. Chem.,  2013, 37, 873-876.
[http://dx.doi.org/10.1039/c3nj40759d] 
[32] 
Joanna, F.K.; Tomczuk, K. The effect of the cationic structures of chiral ionic liquids on their antimicrobial activities. Tetrahedron,  2013, 69, 4190-4198.
[http://dx.doi.org/10.1016/j.tet.2013.03.107] 
[33] 
Walkiewicz, F.; Materna, K.; Kropacz, A.; Michalczyk, A.; Gwiazdowski, R.; Praczykd, T.; Pernak, J. Multifunctional long-alkyl-chain quaternary ammonium azolate based ionic liquids. New J. Chem.,  2010, 34, 2281-2289.
[http://dx.doi.org/10.1039/c0nj00228c] 
[34] 
Łukasz, C. Synthesis of benzoazole ionic liquids and evaluation of their antimicrobial activity. Biomed Biopharm Re.,  2014, 11, 227-235.
[35] 
Cybulski, J.; Wiśniewska, A.; Kulig-Adamiak, A.; Dabrowski, Z.; Praczyk, T.; Michalczyk, A.; Walkiewicz, F.; Materna, K.; Pernak, J. Mandelate and prolinate ionic liquids: synthesis, characterization, catalytic and biological activity. Tetrahedron,  2011, 52, 1325-1328.
[http://dx.doi.org/10.1016/j.tetlet.2011.01.069] 
[36] 
Busetti, A.; Crawford, D.E.; Earle, M.J.; Gilea, M.A.; Gilmore, B.F. Antimicrobial and antibiofilm activities of 1-alkylquinolinium bromide ionic liquids. Green Chem.,  2010, 12, 420-425.
[http://dx.doi.org/10.1039/b919872e] 
[37] 
Siopa, F.; Figueiredo, T.; Frade, R.F.M.; Neto, I.; Meirinhos, A.; Reis, C.P.; Sobral, R.G.; Afonso, C.A.M.; Rijo, P. Choline-based ionic liquids: improvement of antimicrobial activity. ChemistrySelect,  2016, 1, 5909-5916.
[http://dx.doi.org/10.1002/slct.201600864] 
[38] 
Yu, J.; Zhang, S.; Dai, Y.; Lu, X.; Lei, Q.; Fang, W. Antimicrobial activity and cytotoxicity of piperazinium- and guanidinium-based ionic liquids. J. Hazard. Mater.,  2016, 307, 73-81.
[http://dx.doi.org/10.1016/j.jhazmat.2015.12.028] [PMID:  26775108] 
[39] 
Zabielska-Matejuk, J. Stangierska, A. Kot, M. New ammonium- and 1,2,4-triazolium-based ionic liquids for wood preservation. J. Wood Chem. Technol.,  2015, 35, 178-192.
[http://dx.doi.org/10.1080/02773813.2014.909852] 
[40] 
Kubo, A.L.; Kremer, L.; Herrmann, S.; Mitchell, S.G.; Bondarenko, O.M.; Kahru, A.; Streb, C. Antimicrobial activity of polyoxometalate ionic liquids (POM-ILs) against clinically relevant pathogens. ChemPlusChem,  2017, 82, 867-871.
[http://dx.doi.org/10.1002/cplu.201700251] 
[41] 
Ceri, H.; Olson, M.E.; Stremick, C.; Read, R.R.; Morck, D.; Buret, A. The Calgary Biofilm Device: new technology for rapid determination of antibiotic susceptibilities of bacterial biofilms. J. Clin. Microbiol.,  1999, 37(6), 1771-1776.
[PMID:  10325322] 
[42] 
Venkata Nancharaiah, Y.; Reddy, G.K.; Lalithamanasa, P.; Venugopalan, V.P. The ionic liquid 1-alkyl-3-methylimidazolium demonstrates comparable antimicrobial and antibiofilm behavior to a cationic surfactant. Biofouling,  2012, 28(10), 1141-1149.
[http://dx.doi.org/10.1080/08927014.2012.736966] [PMID:  23092364] 
[43] 
Bergamo, V.Z.; Donato, R.K.; Dalla Lana, D.F.; Donato, K.J.Z.; Ortega, G.G.; Schrekker, H.S.; Fuentefria, A.M. Imidazolium salts as antifungal agents: strong antibiofilm activity against multidrug-resistant Candida tropicalis isolates. Lett. Appl. Microbiol.,  2015, 60(1), 66-71.
[http://dx.doi.org/10.1111/lam.12338] [PMID:  25294047] 
[44] 
Reddy, G.K.K.; Nancharaiah, Y.V.; Venugopalan, V.P. Long alkyl-chain imidazolium ionic liquids: antibiofilm activity against phototrophic biofilms. Colloids Surf. B Biointerfaces,  2017, 155, 487-496.
[http://dx.doi.org/10.1016/j.colsurfb.2017.04.040] [PMID:  28475985] 
[45] 
Navale, G.R.; Dharne, M.S.; Shinde, S.S. Antibiofilm activity of tert-BuOH functionalized ionic liquids with methylsulfonate counteranions. RSC Advances,  2015, 5, 68136-68142.
[http://dx.doi.org/10.1039/C5RA12854D] 
[46] 
Jha, G.; Sahu, P.K.; Panda, S.; Singh, D.V.; Patole, S.; Mohapatra, H.; Sarkar, M. Synthesis, photophysical studies on some anthracene-based ionic liquids and their application as biofilm formation inhibitor. ChemistrySelect,  2017, 2, 2426-2432.
[http://dx.doi.org/10.1002/slct.201601964] 
[47] 
Kumar, V.; Malhotra, S.V. Study on the potential anti-cancer activity of phosphonium and ammonium-based ionic liquids. Bioorg. Med. Chem. Lett.,  2009, 19(16), 4643-4646.
[http://dx.doi.org/10.1016/j.bmcl.2009.06.086] [PMID:  19615902] 
[48] 
Kumar, V.; Malhotra, S.V. Antitumor Activity of Ionic
Liquids on Human Tumor Cell Lines In: Ionic Liquid Applications:
Pharmaceuticals, Therapeutics, and Biotechnology; Sanjay, V. Malhotra, Ed.; ACS Symposium Series,, 2010; Vol. 1038, pp. 91-102.
[http://dx.doi.org/10.1021/bk-2010-1038.ch008] 
[49] 
Malhotra, S.V.; Kumar, V.; Velez, C.; Zayas, B. Imidazolium-derived ionic salts induce inhibition of cancerous cell growth through apoptosis. MedChemComm,  2014, 5, 1404-1409.
[http://dx.doi.org/10.1039/C4MD00161C] 
[50] 
Malhotra, S.V.; Kumar, V. A profile of the in vitro anti-tumor activity of imidazolium-based ionic liquids. Bioorg. Med. Chem. Lett.,  2010, 20(2), 581-585.
[http://dx.doi.org/10.1016/j.bmcl.2009.11.085] [PMID:  20006501] 
[51] 
Kaushik, N.K.; Attri, P.; Kaushik, N.; Choi, E.H. Synthesis and antiproliferative activity of ammonium and imidazolium ionic liquids against T98G brain cancer cells. Molecules,  2012, 17(12), 13727-13739.
[http://dx.doi.org/10.3390/molecules171213727] [PMID:  23174892] 
[52] 
Zhang, Z.B.; Fu, S.B.; Duan, H.F.; Lin, Y.J.; Yang, Y. Brand-new function of well-designed ionic liquid: inhibitor of tumor cell growth. Chem. Res. Chin. Univ.,  2010, 26, 757-760.
[53] 
Ferraz, R.; Costa-Rodrigues, J.; Fernandes, M.H.; Santos, M.M.; Marrucho, I.M.; Rebelo, L.P.; Prudêncio, C.; Noronha, J.P.; Petrovski, Ž.; Branco, L.C. PrudÞncio, C.; Noronha, J.P.; Petrovski, Z.; Branco, L.C. Antitumor activity of ionic liquids based on ampicillin. ChemMedChem,  2015, 10(9), 1480-1483.
[http://dx.doi.org/10.1002/cmdc.201500142] [PMID:  26190053] 
[54] 
Ferraz, R.; Costa-Rodrigues, J.; Fernandes, M H.; Santos, M.M.; Marrucho, I.M.; PrudÞncio, C.; Noronha,, J.P.; Petrovski, Z. Synthesis, char-acterization and antiproliferative activity on cancer cell lines of new ionic liquids from ampicillin. Iberic Meeting on Medicinal Chemistry, 2011.http://hdl.handle.net/10400.22/2004
[55] 
Stepnowski, P.; Składanowski, A.C.; Ludwiczak, A.; Laczyńska, E. Evaluating the cytotoxicity of ionic liquids using human cell line HeLa. Hum. Exp. Toxicol.,  2004, 23(11), 513-517.
[http://dx.doi.org/10.1191/0960327104ht480oa] [PMID:  15625776] 
[56] 
Egorova, K.S.; Gordeev, E.G.; Ananikov, V.P. Biological activity of ionic liquids and their application in pharmaceutics and medicine. Chem. Rev.,  2017, 117(10), 7132-7189.
[http://dx.doi.org/10.1021/acs.chemrev.6b00562] [PMID:  28125212] 
[57] 
Arning, J.; Stolte, S.; Böschen, A.; Stock, F.; Pitner, W.R.; Welz-Biermann, U.; Jastorffa, B.; Ranke, J. Qualitative and quantitative structure activity relationships for the inhibitory effects of cationic head groups, functionalised side chains and anions of ionic liquids on acetylcholinesterase. Green Chem.,  2008, 10, 47-58.
[http://dx.doi.org/10.1039/B712109A] 
[58] 
Składanowski, A.C.; Stepnowski, P.; Kleszczyński, K.; Dmochowska, B. AMP deaminase in vitro inhibition by xenobiotics A potential molecular method for risk assessment of synthetic nitro- and polycyclic musks, imidazolium ionic liquids and N-glucopyranosyl ammonium salts. Environ. Toxicol. Pharmacol.,  2005, 19(2), 291-296.
[PMID:  21783488] 
[59] 
Frade, R.F.; Afonso, C.A. Impact of ionic liquids in environment and humans: an overview. Hum. Exp. Toxicol.,  2010, 29(12), 1038-1054.
[http://dx.doi.org/10.1177/0960327110371259] [PMID:  20511289] 
[60] 
Luo, Y.R.; Wang, S.H.; Yun, M.X.; Li, X.Y.; Wang, J.J.; Sun, Z.J. The toxic effects of ionic liquids on the activities of acetylcholinesterase and cellulase in earthworms. Chemosphere,  2009, 77(3), 313-318.
[http://dx.doi.org/10.1016/j.chemosphere.2009.07.026] [PMID:  19682724] 
[61] 
Charana, K.T.P.; Ranjan, P.; Manojkumar, K.; Pothanagandhi, N.; Jha, P.C.; Khedkar, V.M.; Sivaramakrishnaa, A.; Vijayakrishna, K. Evaluation of imidazolium-based ionic liquids towards vermicidal activity: in vitro & in silico studies. RSC Advances,  2015, 5, 75415-75424.
[http://dx.doi.org/10.1039/C5RA13469B] 
[62] 
Charan, K.T.; Pothanagandhi, N.; Manojkumar, K.; Ranjan, P.; Vijayakrishna, K. Notable anti-vermicidal activity of polymeric ionic liquids against Pheretima posthuma. J. Indian Chem. Soc.,  2015, 92, 573-576.
[63] 
Hough-Troutman, W.L.; Smiglak, M.; Griffin, S.; Reichert, W.M.; Mirska, I.; Jodynis-Liebert, J.; Adamska, T.; Nawrot, J.; Stasiewicz, M.; Rogers, R.D.; Pernak, J. Ionic liquids with dual biological function: sweet and anti-microbial, hydrophobic quaternary ammonium-based salts. New J. Chem.,  2009, 33, 26-33.
[http://dx.doi.org/10.1039/B813213P] 
[64] 
Brari, J.; Thakur, D.R. Insecticidal potential properties of citronellol derived ionic liquid against two major stored grain insect pests. J. Entomol. Zool. Stud.,  2016, 4, 365-370.
[65] 
Verma, S.; Kasana, V. Development of novel herbicidal ionic liquids. Int. Res. J. Pure Appl. Chem.,  2017, 15, 1-8.
[http://dx.doi.org/10.9734/IRJPAC/2017/36792] 
[66] 
Pernak, J.; Syguda, A.; Janiszewska, D.; Materna, K.; Praczyk, T. Ionic liquids with herbicidal anions. Tetrahedron,  2011, 67, 4838-4844.
[http://dx.doi.org/10.1016/j.tet.2011.05.016] 
[67] 
Pernak, J.; Syguda, A.; Materna, K.; Janus, E.; Kardasz, P.; Praczyk, T. 2,4-D based herbicidal ionic liquids. Tetrahedron,  2012, 68, 4267-4273.
[http://dx.doi.org/10.1016/j.tet.2012.03.065] 
[68] 
Pernak, J.; Niemczak, M.; Materna, K.; Zelechowski, K.; Marcinkowska, K.; Praczyk, T. Synthesis, properties and evaluation of biological activity of herbicidal ionic liquids with 4-(4-chloro-2-methylphenoxy) butanoate anion. Rsc Adv.,  2016, 6, 7330-7338.
[http://dx.doi.org/10.1039/C5RA23997D] 
[69] 
Pernak, J.; Niemczak, M.; Giszter, R.; Shamshina, J.L.; Gurau, G.; Cojocaru, O.A.; Praczyk, T.; Marcinkowska, K.; Rogers, R.D. Glyphosate-based herbicidal ionic liquids with increased efficacy. ACS Sustain. Chem.& Eng.,  2014, 2, 2845-2851.
[http://dx.doi.org/10.1021/sc500612y] 
[70] 
Cojocaru, O.A.; Shamshina, J.; Gurau, G.; Syguda, A.; Praczyk, T.; Pernak, J.; Rogers, R.D. Ionic liquid forms of the herbicide dicamba with increased efficacy and reduced volatility. Green Chem.,  2013, 15, 2110-2120.
[http://dx.doi.org/10.1039/c3gc37143c] 
[71] 
Pernak, J.; Giszter, R.; Biedziak, A.; Niemczak, M.; Olszewski, R.; Marcinkowska, K.; Praczyk, T. Alkyl(C16, C18, C22)trimethylammonium-based herbicidal ionic liquids. J. Agric. Food Chem.,  2017, 65(2), 260-269.
[http://dx.doi.org/10.1021/acs.jafc.6b04528] [PMID:  27997185] 
[72] 
Hanatani, A.; Washiro, S. Preparation for external use
comprising an ionic liquid  EP1795188.  2006.
[73] 
Julia, L.S.; Steven, P.K.; Gabriela, G.; Robin, D.R. Chemistry: develop ionic liquid drugs. Nature,  2015, 528(7581), 188-189.
[74] 
Karpinski, P.H. Polymorphism of active pharmaceutical ingredients. Chem. Eng. Technol.,  2006, 29, 233-237.
[http://dx.doi.org/10.1002/ceat.200500397] 
[75] 
Ferraz, R.; Branco, L.C.; Prudêncio, C.; Noronha, J.P.; Petrovski, Z. Ionic liquids as active pharmaceutical ingredients. ChemMedChem,  2011, 6(6), 975-985.
[http://dx.doi.org/10.1002/cmdc.201100082] [PMID:  21557480] 
[76] 
Balk, A.; Holzgrabe, U.; Meinel, L. ‘Pro et contra’ ionic liquid drugs - Challenges and opportunities for pharmaceutical translation. Eur. J. Pharm. Biopharm.,  2015, 94, 291-304.
[http://dx.doi.org/10.1016/j.ejpb.2015.05.027] [PMID:  26070389] 
[77] 
Whitney, L.H.; Marcin, S.; Hector, R.; Richard, P.S.; Scott, K.S.; Daniel, T.D.; Juliusz, P.; Judith, E.G. The third evolution of ionic liquids: active pharmaceutical ingredients. New J. Chem.,  2007, 31, 1429-1436.
[http://dx.doi.org/10.1039/b706677p] 
[78] 
Marsha, R.C.; Min, L.; Bilal, E.Z.; Marlene, E.J.; Daniel, H.; Isiah, M.W. Design, synthesis, and biological evaluation of β-lactam antibiotic-based imidazolium-and pyridinium-type ionic liquids. Chem. Biol. Drug Des.,  2011, 78(1), 33-41.
[http://dx.doi.org/10.1111/j.1747-0285.2011.01114.x] [PMID:  21443681] 
[79] 
Ferraz, R.; Teixeira, V.; Rodrigues, D. Antibacterial activity of Ionic Liquids based on ampicillin against resistant bacteria. Rsc Adv.,  2013, 4, 4301-4307.
[http://dx.doi.org/10.1039/C3RA44286A] 
[80] 
Balk, A.; Wiest, J.; Widmer, T.; Galli, B.; Holzgrabe, U.; Meinel, L. Transformation of acidic poorly water soluble drugs into ionic liquids. Eur. J. Pharm. Biopharm.,  2015, 94, 73-82.
[http://dx.doi.org/10.1016/j.ejpb.2015.04.034] [PMID:  25976317] 
[81] 
Shadid, M.; Gurau, G.; Shamshina, J.L.; Chuang, B.C.; Hailu, S.; Guan, E.; Chowdhury, S.; Wu, J.T.; Rizvi, S.A.A.; Griffin, R.J.; Rogers, R.D. Sulfasalazine in ionic liquid form with improved solubility and exposure. MedChemComm,  2013, 6, 1837-1841.
[http://dx.doi.org/10.1039/C5MD00290G] 
[82] 
Bica, K.; Shamshina, J.; Hough, W.L.; MacFarlane, D.R.; Rogers, R.D. Liquid forms of pharmaceutical co-crystals: exploring the boundaries of salt formation. Chem. Commun. (Camb.),  2011, 47(8), 2267-2269.
[http://dx.doi.org/10.1039/C0CC04485G] [PMID:  21161097] 
[83] 
Whitney, L.H.; Robin, D.R. Ionic liquids then and now: from solvents to materials to active pharmaceutical ingredients. Bull. Chem. Soc. Jpn.,  2007, 80, 2262-2269.
[http://dx.doi.org/10.1246/bcsj.80.2262] 
[84] 
Stoimenovski, J.; MacFarlane, D.R.; Bica, K.; Rogers, R.D. Crystalline vs. ionic liquid salt forms of active pharmaceutical ingredients: a position paper. Pharm. Res.,  2010, 27(4), 521-526.
[http://dx.doi.org/10.1007/s11095-009-0030-0] [PMID:  20143257] 
[85] 
Jason, P.H.; Tom, W. Room-temperature Ionic Liquids: solvents for synthesis and catalysis. 2. Chem. Rev.,  2011, 111(5), 3508-3576.
[http://dx.doi.org/10.1021/cr1003248] [PMID:  21469639] 
[86] 
Cinzia, C.; Daniela, P. Ionic liquids: solvent properties and organic reactivity. J. Phys. Org. Chem.,  2005, 18, 275-297.
[http://dx.doi.org/10.1002/poc.863] 
[87] 
Sheldon, R. Catalytic reactions in ionic liquids. Chem. Commun. (Camb.),  2001, 23(23), 2399-2407.
[http://dx.doi.org/10.1039/b107270f] [PMID:  12239988] 
[88] 
Colin, D.H.; Peter, I.; Rudi, V.E. Understanding chemical reaction mechanisms in ionic liquids: successes and challenges. Chem. Soc. Rev.,  2011, 40(1), 272-290.
[http://dx.doi.org/10.1039/C0CS00043D] [PMID:  21079861] 
[89] 
Katharina, B.; Peter, G. Applications of chiral ionic liquids. Eur. J. Org. Chem.,  2008, 3235-3250.
[90] 
Liu, Y.; Meyer, A.S.; Nie, Y.; Zhang, S.; Thomsen, K. Low energy recycling of ionic liquids via freeze crystallization during cellulose spinning. Green Chem.,  2017, 20, 493-501.
[http://dx.doi.org/10.1039/C7GC02880F] 
[91] 
Haerens, K.; Deuren, S.V.; Matthijs, E.; Bruggen, B.V. Challenges for recycling ionic liquids by using pressure driven membrane processes. Green Chem.,  2010, 12, 2182-2188.
[http://dx.doi.org/10.1039/c0gc00406e] 
[92] 
Lu, J.; He, A.; Li, S.Y.; Nie, L.R.; Zhang, W.; Yao, S. Synthesis, purification and recycling of ionic liquid: a review. Mini Rev. Org. Chem.,  2015, 12, 435-448.
[http://dx.doi.org/10.2174/1570193X13666151125230810] 
[93] 
Shallu.; Sharma, M.L.; Singh, J. First total synthesis of a guanidine alkaloid nitensidine D using immobilized ionic liquid, microwaves and formamidinesulfinic acid. J. Chem. Sci.,  2014, 126, 1869-1874.
[http://dx.doi.org/10.1007/s12039-014-0723-8] 
[94] 
Martins, P.L.G.; Braga, A.R.; Rosso, V.V.D. Can ionic liquid solvents be applied in the food industry? Trends Food Sci. Technol.,  2017, 66, 117-124.
[http://dx.doi.org/10.1016/j.tifs.2017.06.002] 
[95] 
Chand, M.M.; Shukla, A.K. Novel synthesis of bicalutamide drug substance and their impurities using imidazolium type of ionic liquid. Soc. Sci. Electron. Pub.,  2012, 12, 4142-4151.
[96] 
Kameshwara, V.; Bhupender, S.C.; Rakesh, T.; Amir, N.S.; Keykavous, P.; Anil, K. One-pot regioselective synthesis of tetrahydroindazolones and evaluation of their antiproliferative and Src kinase inhibitory activities. Bioorg. Med. Chem. Lett.,  2012, 22(11), 410-414.
[http://dx.doi.org/10.1016/j.bmcl.2011.10.124] [PMID:  22119472] 
[97] 
Vineet, K.; Sanjay, V. M. Synthesis of nucleoside-based antiviral drugs in ionic liquids. Bioorg. Med. Chem. Lett.,  2008, 18(), 5640-5642.
[http://dx.doi.org/10.1016/j.bmcl.2008.08.090] [PMID:  18796352] 
[98] 
Alireza, B.; Vikneswaran, M.; Hasnah, O.; Raju, S.K.; Yalda, K.; Khalijah, B.A.; Mohamed, A.A. An expedient, ionic liquid mediated multi-component synthesis of novel piperidone grafted cholinesterase enzymes inhibitors and their molecular modeling study. Eur. J. Med. Chem.,  2013, 67, 221-229.
[http://dx.doi.org/10.1016/j.ejmech.2013.06.054] [PMID:  23871902] 
[99] 
Monika, G. Efficient synthesis of antifungal active 9-substituted-3-aryl-5H, 13aH-quinolino[3,2-f][1,2,4]triazolo[4,3-b][1,2,4]triazepines in ionic liquids. Bioorg. Med. Chem. Lett.,  2011, 21(16), 4919-4923.
[http://dx.doi.org/10.1016/j.bmcl.2011.06.007] [PMID:  21763133] 
[100] 
Trissa, J.; Suman, S. Bronsted acidic ionic liquids: A green, efficient and reusable catalyst system and reaction medium for Fischer esterification. J. Mol. Catal. Chem.,  2005, 234, 107-110.
[http://dx.doi.org/10.1016/j.molcata.2005.03.005] 
[101] 
Pralhad, A.G.; Gigi, G.; Jagannath, D. Brønsted acidic ionic liquids derived from alkylamines as catalysts and mediums for Fischer esterification: Study of structure–activity relationship. J. Mol. Catal. Chem.,  2008, 279, 182-186.
[http://dx.doi.org/10.1016/j.molcata.2007.06.025] 
[102] 
Jasvinder, S.; Neeraj, G.; Goverdhan, L.K. Efficient role of ionic liquid (bmim)HSO4 as novel catalyst for monotetrahydropyranylation of diols and tetrahydropyranylation of alcohols. Synth. Commun.,  2006, 36, 2893-2900.
[http://dx.doi.org/10.1080/00397910600770839] 
[103] 
Yanlong, G.; Feng, S.; Youquan, D. Esterification of aliphatic acids with olefin promoted by Brønsted acidic ionic liquids. J. Mol. Catal. Chem.,  2004, 212, 71-75.
[http://dx.doi.org/10.1016/j.molcata.2003.10.039] 
[104] 
Song, Y.L.; Wu, F.; Zhang, C.C.; Liang, G.C.; Zhou, G.; Yu, J.J. Ionic liquid catalyzed synthesis of 2-(indole-3-yl)-thiochroman-4-ones and their novel antifungal activities. Bioorg. Med. Chem. Lett.,  2015, 25(2), 259-261.
[http://dx.doi.org/10.1016/j.bmcl.2014.11.056] [PMID:  25499881] 
[105] 
Dake, S.A.; Raut, D.S.; Kharat, K.R.; Mhaske, R.S.; Deshmukh, S.U.; Pawar, R.P. Ionic liquid promoted synthesis, antibacterial and in vitro antiproliferative activity of novel α-aminophosphonate derivatives. Bioorg. Med. Chem. Lett.,  2011, 21(8), 2527-2532.
[http://dx.doi.org/10.1016/j.bmcl.2011.02.039] [PMID:  21398120] 
[106] 
Suresh; Jagir, S.S. Ultrasound-assisted synthesis of 2,4-thiazolidinedione and rhodanine derivatives catalyzed by task-specific ionic liquid.[TMG][Lac]. Org. Med. Chem. Lett.,  2013, 3, 2.
[http://dx.doi.org/10.1186/2191-2858-3-2] [PMID:  23458122] 
[107] 
Wang, Z.T.; Wang, S.C.; Xu, L.W. Polymer‐Supported ionic liquid catalyzed synthesis of 1,2,3,4‐tetrahydro‐2‐oxopyrimidine‐5‐carboxylates via biginelli reaction. ChemInform,  2005, 36, 986-989.
[http://dx.doi.org/10.1002/chin.200541157] 
[108] 
Hagiwara, H.; Nakamura, T.; Okunaka, N.; Hoshi, T.; Suzuki, T. Catalytic performance of ruthenium-supported ionic-liquid catalysts in sustainable synthesis of macrocyclic lactones. ChemInform,  2010, 93, 175-182.
[109] 
Singer, R.D.; Scammells, P.J. Alternative methods for the MnO2 oxidation of codeine methyl ether to thebaine utilizing ionic liquids. Tetrahedron Lett.,  2001, 42, 6831-6833.
[http://dx.doi.org/10.1016/S0040-4039(01)01383-1] 
[110] 
Kort, M.D.; Tuin, A.W.; Kuiper, S.; Overkleeft, H.S.; Marel, G.A.; Buijsman, R.C. Development of a novel ionic support and its application in the ionic liquid phase assisted synthesis of a potent antithrombotic. Tetrahedron Lett.,  2004, 45, 2171-2175.
[http://dx.doi.org/10.1016/j.tetlet.2004.01.032] 
[111] 
MA.Wang, J.J.; Zang, C.; Zhou, X.H.; Wang, X.; Gao, Z.; Cui, Y.J.; Wu, P.L.; Song, Q.H.; J, S. Synthesis of 5-arylidenebarbituric acid derivatives promoted by room temperature ionic liquid. Youji Huaxue,  2006, 26, 723-726.
[112] 
Liu, H.X.; Qun, X.U. Ionic liquids used as microwave absorbent to promote the konoevenagel condensation reaction of benzaldehyde and barbituric acid. Chemical Res Appl.,  2007, 19, 608-610.
[113] 
Webb, P.B.; Sellin, M.F.; Kunene, T.E.; Williamson, S.; Slawin, A.M.; Cole-Hamilton, D.J. Continuous flow hydroformylation of alkenes in supercritical fluid-ionic liquid biphasic systems. J. Am. Chem. Soc.,  2003, 125(50), 15577-15588.
[http://dx.doi.org/10.1021/ja035967s] [PMID:  14664605] 
[114] 
Zhao, Y.; Yao, C.; Chen, G.; Yuan, Q. Highly efficient synthesis of cyclic carbonate with CO2 catalyzed by ionic liquid in a microreactor. Green Chem.,  2013, 15, 446-452.
[http://dx.doi.org/10.1039/C2GC36612F] 
[115] 
Chen, A.Y.; Chen, Y.C. A review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention. Food Chem.,  2013, 138(4), 2099-2107.
[http://dx.doi.org/10.1016/j.foodchem.2012.11.139] [PMID:  23497863] 
[116] 
Plochmann, K.; Korte, G.; Koutsilieri, E.; Richling, E.; Riederer, P.; Rethwilm, A.; Schreier, P.; Scheller, C. Structure-activity relationships of flavonoid-induced cytotoxicity on human leukemia cells. Arch. Biochem. Biophys.,  2007, 460(1), 1-9.
[http://dx.doi.org/10.1016/j.abb.2007.02.003] [PMID:  17353006] 
[117] 
Cai, Y.Z.; Mei, Sun; Jie, Xing.; Luo, Q.; Corke, H. Structure-radical scavenging activity relationships of phenolic compounds from traditional Chinese medicinal plants. Life Sci.,  2006, 78(25), 2872-2888.
[http://dx.doi.org/10.1016/j.lfs.2005.11.004] [PMID:  16325868] 
[118] 
Amaral, S.; Mira, L.; Nogueira, J.M.; da Silva, A.P.; Helena Florêncio, M. Plant extracts with anti-inflammatory properties--a new approach for characterization of their bioactive compounds and establishment of structure-antioxidant activity relationships. Bioorg. Med. Chem.,  2009, 17(5), 1876-1883.
[http://dx.doi.org/10.1016/j.bmc.2009.01.045] [PMID:  19201196] 
[119] 
Brunskole, M.; Zorko, K.; Kerbler, V.; Martens, S.; Stojan, J.; Gobec, S.; Lanisnik Rizner, T. Trihydroxynaphthalene reductase of Curvularia lunata--a target for flavonoid action? Chem. Biol. Interact.,  2009, 178(1-3), 259-267.
[http://dx.doi.org/10.1016/j.cbi.2008.10.023] [PMID:  19010313] 
[120] 
Wang, J.; Gong, A.; Yang, C.F.; Bao, Q.; Shi, X.Y.; Han, B.B.; Wu, X.Y.; Wu, F.A. An effective biphase system accelerates hesperidinase-catalyzed conversion of rutin to isoquercitrin. Sci. Rep.,  2015, 5, 8682.
[http://dx.doi.org/10.1038/srep08682] [PMID:  25731802] 
[121] 
Katsoura, M.H.; Polydera, A.C.; Tsironis, L.; Tselepis, A.D.; Stamatis, H. Use of ionic liquids as media for the biocatalytic preparation of flavonoid derivatives with antioxidant potency. J. Biotechnol.,  2006, 123(4), 491-503.
[http://dx.doi.org/10.1016/j.jbiotec.2005.12.022] [PMID:  16457903] 
[122] 
Lue, B.M.; Guo, Z.; Xu, X. Effect of room temperature ionic liquid structure on the enzymatic acylation of flavonoids. Process Biochem.,  2010, 45, 1375-1382.
[http://dx.doi.org/10.1016/j.procbio.2010.05.024] 
[123] 
Bukhari, S.N.; Jasamai, M.; Jantan, I. Synthesis and biological evaluation of chalcone derivatives (mini review). Mini Rev. Med. Chem.,  2012, 12(13), 1394-1403.
[PMID:  22876958] 
[124] 
Ahmad, W.; Jantan, I.; Jasamai, M.; Bukhari, S.N. Review of methods and various catalysts used for chalcone synthesis. Org. Chem.,  2013, 10, 73-83.
[125] 
Shen, J.; Wang, H.; Liu, H.; Sun, Y.; Liu, Z. Brønsted acidic ionic liquids as dual catalyst and solvent for environmentally friendly synthesis of chalcone. J. Mol. Catal. Chem.,  2008, 280, 24-28.
[http://dx.doi.org/10.1016/j.molcata.2007.10.021] 
[126] 
Megan, T.T.; Luke, C.H.; Nolene, B.; Frederick, M.P. Accessing highly-halogenated flavanones using protic ionic liquids and microwave irradiation. Curr. Org. Chem.,  2012, 16, 121-126.
[http://dx.doi.org/10.2174/138527212798993167] 
[127] 
Theodosiou, E.; Katsoura, M.H.; Loutrari, H. Purchartovã¡, H. Enzymatic preparation of acylated derivatives of silybin in organic and ionic liquid media and evaluation of their antitumor proliferative activity. Biocatal. Biotransform.,  2009, 27, 161-169.
[http://dx.doi.org/10.1080/10242420902937777] 
[128] 
Katsoura, M.H.; Polydera, A.C.; Katapodis, P.; Kolisis, F.N.; Stamatis, H. Effect of different reaction parameters on the lipase-catalyzed selective acylation of polyhydroxylated natural compounds in ionic liquids. Process Biochem.,  2007, 42, 1326-1334.
[http://dx.doi.org/10.1016/j.procbio.2007.07.004] 
[129] 
Raab, T.; Chaillot, D.; Hansen, C.E.; Williamson, G.; Bel-Rhlid, R.; Chaillot, D. Enzymatic galloylation of catechins in room temperature ionic liquids. J. Mol. Catal., B Enzym.,  2007, 44, 60-65.
[http://dx.doi.org/10.1016/j.molcatb.2006.09.003] 
[130] 
de Araújo, M.E.; Contesini, F.J.; Franco, Y.E.; Sawaya, A.C.; Alberto, T.G.; Dalfré, N. Carvalho, Pde.O. Optimized enzymatic synthesis of hesperidin fatty acid esters in a two-phase system containing ionic liquid. Molecules,  2011, 16(8), 7171-7182.
[http://dx.doi.org/10.3390/molecules16087171] [PMID:  21862958] 
[131] 
Gu, S.S.; Wang, J.; Wang, X.B.; Chen, H.S.; Wang, X.Y.; Wang, F.A. Enhancement of lipase-catalyzed synthesis of caffeic acid phenethyl ester in ionic liquid with DMSO co-solvent. Chin. J. Chem. Eng.,  2014, 22, 1314-1321.
[http://dx.doi.org/10.1016/j.cjche.2014.09.024] 
[132] 
Na, P.; Gu, S.S.; Wang, J.; Chen, H.S.; Xi, L.; Zhang, X.Y.; Wang, F.A. A novel chemoenzymatic synthesis of propyl caffeate using lipase -catalyzed transesterification in ionic liquid. Bioresour. Technol.,  2013, 139, 337-342.
[http://dx.doi.org/10.1016/j.biortech.2013.04.057] [PMID:  23665696] 
[133] 
Kurata, A.; Takemoto, S.; Fujita, T. Synthesis of 3 -cyclohexylpropyl caffeate from 5 -caffeoy -lquinic acid with consecutive enzymatic conversions in ionic liquid. J. Mol. Catal., B Enzym.,  2011, 69, 161-167.
[http://dx.doi.org/10.1016/j.molcatb.2011.01.012] 
[134] 
Wang, J.; Li, J.; Zhao, L.X.; Wang, F.A. Lipase -catalyzed synthesis of caffeic acid phenethyl ester in ionic liquids: effect of specific ions and reaction parameters. Chin. J. Chem. Eng.,  2013, 21, 1376-1385.
[http://dx.doi.org/10.1016/S1004-9541(13)60563-7] 
[135] 
Kurata, A.; Kitamura, Y.; Irie, S.; Takemoto, S.; Akai, Y.; Hirota, Y.; Fujita, T.; Iwai, K.; Furusawa, M.; Kishimoto, N. Enzymatic synthesis of caffeic acid phenethyl ester analogues in ionic liquid. J. Biotechnol.,  2010, 148(2-3), 133-138.
[http://dx.doi.org/10.1016/j.jbiotec.2010.05.007] [PMID:  20553773] 
[136] 
Ha, S.H.; Anh, T.V.; Lee, S.H.; Koo, Y.M. Effect of ionic liquids on enzymatic synthesis of caffeic acid phenethyl ester. Bioprocess Biosyst. Eng.,  2012, 35(1-2), 235-240.
[http://dx.doi.org/10.1007/s00449-011-0601-4] [PMID:  21909673] 
[137] 
Sun, S.; Yang, G.; Bi, Y.; Xiao, F. Chemoenzymatic synthesis of feruloylated monoacyl- and diacyl-glycerols in ionic liquids. Biotechnol. Lett.,  2009, 31(12), 1885-1889.
[http://dx.doi.org/10.1007/s10529-009-0086-2] [PMID:  19633814] 
[138] 
Sun, S.; Qin, F.; Bi, Y.; Chen, J.; Yang, G.; Liu, W. Enhanced transesterification of ethyl ferulate with glycerol for preparing glyceryl diferulate using a lipase in ionic liquids as reaction medium. Biotechnol. Lett.,  2013, 35(9), 1449-1454.
[http://dx.doi.org/10.1007/s10529-013-1222-6] [PMID:  23690034] 
[139] 
Chen, B.L.; Liu, H.Z.; Guo, Z.; Huang, J.; Wang, M.Z.; Xue, X.B.; Zheng, L.F. Lipase-catalyzed esterification of ferulic acid with oleyl alcohol in ionic liquid/isooctane binary systems. J. Agric. Food Chem.,  2011, 59(4), 1256-1263.
[140] 
Shi, Y.G.; Wu, Y.; Lu, X.Y.; Ren, Y.P.; Wang, Q.; Zhu, C.M.; Yu, D.; Wang, H. Lipase-catalyzed esterification of ferulic acid with lauryl alcohol in ionic liquids and antibacterial properties in vitro against three food-related bacteria. Food Chem.,  2017, 220, 249-256.
[http://dx.doi.org/10.1016/j.foodchem.2016.09.187] [PMID:  27855896] 
[141] 
Wang, J.; Gu, S.S.; Cui, H.S.; Yang, L.Q.; Wu, X.Y. Rapid synthesis of propyl caffeate in ionic liquid using a packed bed enzyme microreactor under continuous-flow conditions. Bioresour. Technol.,  2013, 149, 367-374.
[http://dx.doi.org/10.1016/j.biortech.2013.09.098] [PMID:  24128399] 
Rights & Permissions Print Cite
Article Metrics
44
1
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/0929867325666180605123436	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
Current Medicinal Chemistry

Ionic Liquid-Like Pharmaceutical Ingredients and Applications of Ionic Liquids in Medicinal Chemistry: Development, Status and Prospects

Abstract Play Pause

Related Journals

Related Books

Abstract
