Abstract
Two meta-xylyl linked tetrakis-benzimidazolium salts (L1-L2) as multidentate ligands and two respective silver complexes (C1 and C2) were synthesized. A multistep reaction was done at room temperature, starting with simple benzimidazole and alkyl halides, going through precursors and salt formation by reflux and finally in situ deprotonation of tetrabenzimidazolium salts with Ag2O to yield respective tetra-nuclear Ag(I)-N-heterocyclic Carbene (NHC) complexes. Propyl and butyl groups were bonded at the terminal positions of tetra-azolium open chain salts. Characterization of compounds was done by analytical and spectroscopic techniques. On the basis of spectroscopic data, a chemical structure with open chains having four Ag(I) ions sandwiched between NHC layers was established. Potential of synthesized complexes (C1 & C2) for wound contraction was evaluated and compared with standard wound contraction gel. Percentage wound contraction of both complexes was found very close to that of standard drug used in parallel.
Funding source: Higher Education Commision, Pakistan
Award Identifier / Grant number: NRPU-8396
Acknowledgment
First author is thankful to Higher Education Commission (HEC) of Pakistan, for awarding scholarships under projects “Indigenous PhD fellowship for 5000 scholars” Phase-II, Batch-I, 2012 wide No: 17-5(2Ps1-016/HEC/IS-2/2013 and “International Research Support Initiative Program (2017)” wide No: 1-8/HEC/HRD/2017/6925. Dr. M.A. Iqbal is thankful to Higher Education Commission of Pakistan (HEC-Pak) for awarding research grant NRPU-8396.
Author contribution: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: NRPU-8396.
Employment or leadership: None declared.
Honorarium: None declared.
Conflict of Interest: The authors declare no conflict of interest.
References
1. Hahn, FE. Heterocyclic carbenes. Angew Chem Int Ed 2006;45(9):1348–52. https://doi.org/10.1002/anie.200503858.Search in Google Scholar PubMed
2. Arduengo, AJ, Harlow, RL, Kline, M. A stable crystalline carbene. J Am Chem Soc 1991;113(1):361–3. https://doi.org/10.1021/ja00001a054.Search in Google Scholar
3. Wanzlick, H. Aspects of nucleophilic carbene chemistry. Angew Chem Int Ed 1962;1(2):75–80. https://doi.org/10.1002/anie.196200751.Search in Google Scholar
4. Wanzlick, HW, Esser, F, Kleiner, HJ. Nucleophile Carben-Chemie, III. Neue Verbindungen vom Typ des Bis-[1.3-diphenyl-imidazolidinylidens-(2)]. Chem Ber 1963;96(5):1208–12. https://doi.org/10.1002/cber.19630960505.Search in Google Scholar
5. ArduengoIIIAJ, Dias, HR, Calabrese, JC, Davidson, F. Homoleptic carbene-silver (I) and carbene-copper (I) complexes. Organometallics 1993;12(9):3405–9. https://doi.org/10.1021/om00033a009.Search in Google Scholar
6. Budagumpi, S, Haque, RA, Endud, S, Rehman, GU, Salman, AW. Biologically relevant silver (I)–N-heterocyclic carbene complexes: synthesis, structure, intramolecular interactions, and applications. Eur J Inorg Chem 2013;2013(25):4367–88. https://doi.org/10.1002/ejic.201300483.Search in Google Scholar
7. Haque, RA, Zulikha, HZ, Ghdhayeb, MZ, Budagumpi, S, Salman, AW. Cationic nitrile-functionalized Ag (I)- and Hg (II)-N-heterocyclic carbene complexes of CCC, CNC, and NCN pincer-type carbene ligands: Synthesis, crystal structures, and characterization. Heteroat Chem 2012;23(5):486–97. https://doi.org/10.1002/hc.21041.Search in Google Scholar
8. Cheng, C-H, Chen, D-F, Song, H-B, Tang, L-F. Synthesis and catalytic activity of N-heterocyclic carbene silver complexes derived from 1-[2-(pyrazol-1-yl)phenyl]imidazole. J Organomet Chem 2013;726:1–8. https://doi.org/10.1016/j.jorganchem.2012.12.008.Search in Google Scholar
9. Wang, Z, Wen, J, Bi, Q-W, Xu, X-Q, Shen, Z-Q, Li, X-X, Chen, Z. Oxirane synthesis from diazocarbonyl compounds via NHC-Ag+ catalysis. Tetrahedron Lett 2014;55(18):2969–72. https://doi.org/10.1016/j.tetlet.2014.03.105.Search in Google Scholar
10. Haque, RA, Salman, AW, Budagumpi, S, Abdullah, AA-A, Majid, AMSA. Sterically tuned Ag(i)- and Pd(ii)-N-heterocyclic carbene complexes of imidazol-2-ylidenes: synthesis, crystal structures, and in vitro antibacterial and anticancer studies. Metallomics 2013;5(6):760–9. https://doi.org/10.1039/c3mt00051f.Search in Google Scholar PubMed
11. Haque, RA, Haziz, UFM, Amirul, AA, Shaheeda, N, Razali, MR. Synthesis of a palladium(II) complex of a N-heterocylic carbene via transmetalation: crystal structure and antibacterial studies. Transit Met Chem 2016;41(7):775–81. https://doi.org/10.1007/s11243-016-0078-8.Search in Google Scholar
12. Park, KH, Ku, I, Kim, HJ, Son, SU. NHC-Based Submicroplatforms for Anchoring Transition Metals. Chem Mater 2008;20(5):1673–5. https://doi.org/10.1021/cm702776r.Search in Google Scholar
13. Huda Noor, u, Islam, S, Zia, M, William, K, Abbas, FI, Umar, MI., et al. Anticancer, antimicrobial and antioxidant potential of sterically tuned bis-N-heterocyclic salts. Zeitschrift für Naturforschung C 2018;74(1-2):17–23. https://doi.org/10.1515/znc-2018-0095.Search in Google Scholar PubMed
14. Iqbal, MA, Umar, MI, Haque, RA, Khadeer Ahamed, MB, Asmawi, MZB., Majid, AMSA. Macrophage and colon tumor cells as targets for a binuclear silver(I) N-heterocyclic carbene complex, an anti-inflammatory and apoptosis mediator. J Inorg Biochem 2015;146:1–13. https://doi.org/10.1016/j.jinorgbio.2015.02.001.Search in Google Scholar PubMed
15. Garrison, JC, Tessier, CA, Youngs, WJ. Synthesis and crystallographic characterization of multi-donor N-heterocyclic carbene chelating ligands and their silver complexes: potential use in pharmaceuticals. J Organomet Chem 2005;690(24):6008–20. https://doi.org/10.1016/j.jorganchem.2005.07.102.Search in Google Scholar
16. Sakamoto, R, Morozumi, S, Yanagawa, Y, Toyama, M, Takayama, A, Kasuga, NC, et al. Synthesis, characterization, and structure–activity relationship of the antimicrobial activities of dinuclear N-heterocyclic carbene (NHC)-silver(I) complexes. J Inorg Biochem 2016;163:110–7. https://doi.org/10.1016/j.jinorgbio.2016.06.031.Search in Google Scholar PubMed
17. Habib, A, Iqbal, MA, Bhatti, HN. Polynuclear Ag(I)-N-heterocyclic carbene complexes: synthesis, electrochemical and in vitro anticancer study against human breast cancer and colon cancer. J Coord Chem 2019;72(12):2065–79. https://doi.org/10.1080/00958972.2019.1632837.Search in Google Scholar
18. Kamal, A, Nazari, V M, Yaseen, M, Iqbal, MA, Ahamed, MBK, Majid, ASA, et al. Green synthesis of selenium-N-heterocyclic carbene compounds: Evaluation of antimicrobial and anticancer potential. Bioorg Chem 2019;90:103042. https://doi.org/10.1016/j.bioorg.2019.103042.Search in Google Scholar PubMed
19. Habib, A, Mansoureh NazariV, Iqbal, MA, Bhatti, HN, Ahmed, MBK, Majid, AMSA. Unsymmetrically substituted benzimidazolium based Silver(I)-N-heterocyclic carbene complexes: synthesis, characterization and in vitro anticancer study against human breast cancer and colon cancer. J Saudi Chem Soc 2019; 23(7): 795–808. https://doi.org/10.1016/j.jscs.2019.03.002.Search in Google Scholar
20. Habib, A, Iqbal, MA, Bhatti, HN, Shahid, M. Effect of ring substitution on synthesis of benzimidazolium salts and their silver(I) complexes: characterization, electrochemical studies and evaluation of anticancer potential. Transit Met Chem 2019;44(5):431–43. https://doi.org/10.1007/s11243-019-00321-7.Search in Google Scholar
21. Iqbal, MA, Haque, RA, Ahamed, MBK, Majid, AMSA, Al-Rawi, SS. Synthesis and anticancer activity of para-xylyl linked bis-benzimidazolium salts and respective Ag(I) N-heterocyclic carbene complexes. Med Chem Res 2013;22(5):2455–66. https://doi.org/10.1007/s00044-012-0240-6.Search in Google Scholar
22. Haque, RA, Iqbal, MA, Khadeer Ahamed, MB, Majid, AA, Abdul Hameed, ZA. Design, synthesis and structural studies of meta-xylyl linked bis-benzimidazolium salts: potential anticancer agents against ‘human colon cancer’. Chem Cent J 2012;6(1):68. https://doi.org/10.1186/1752-153x-6-68.Search in Google Scholar PubMed PubMed Central
23. Kascatan-Nebioglu, A, Panzner, MJ, Tessier, CA, Cannon, CL, Youngs, WJ. N-Heterocyclic carbene–silver complexes: a new class of antibiotics. Coord Chem Rev 2007;251(5-6):884–95. https://doi.org/10.1016/j.ccr.2006.08.019.Search in Google Scholar
24. Fatima, T, Haque, RA, Razali, MR, Ahmad, A, Iqbal, MA, Asif, M, et al. Synthesis, crystal structure, in vitro anticancer and in vivo acute oral toxicity studies of tetramethylene linked bis-benzimidazolium salts and their respective dinuclear Ag(I)–NHC complexes. J Coord Chem 2016;69(22):3367–83. https://doi.org/10.1080/00958972.2016.1230670.Search in Google Scholar
25. Melaiye, A, Simons, RS, Milsted, A, Pingitore, F, Wesdemiotis, C, Tessier, CA, et al. Formation of water-soluble pincer silver(I)−carbene complexes: a novel antimicrobial agent. J Med Chem 2004;47(4):973–7. https://doi.org/10.1021/jm030262m.Search in Google Scholar PubMed
26. Fatima, T, Haque, RA, Iqbal, MA, Ahmad, A, Hassan, LEA., Taleb-Agha, M, et al. Tetra N-heterocyclic carbene dinuclear silver(I) complexes as potential anticancer agents: Synthesis and in vitro anticancer studies. J Organomet Chem 2017;853:122–35. https://doi.org/10.1016/j.jorganchem.2017.10.045.Search in Google Scholar
27. Fatima, T, Haque, RA, Razali, MR. A new strategy towards tridentate N-heterocyclic carbene ligands derived from benzimidazolium and mixed-azolium salt. J Mol Struct 2017;1141:346–50. https://doi.org/10.1016/j.molstruc.2017.03.097.Search in Google Scholar
28. Selvarajoo, PD, Haque, RA, Haziz, UFM, Avicor, SW, Wajidi, MFF, Razali, MR. Dinuclear silver(I)-N-heterocyclic carbene complexes: Synthesis, characterization and larvicidal activity of bis-imidazolium dinuclear silver(I)-N-heterocyclic carbene complexes. J Inorg Biochem 2017;175:232–8. https://doi.org/10.1016/j.jinorgbio.2017.07.030.Search in Google Scholar PubMed
29. Hu, X, Tang, Y, Gantzel, P, Meyer, K. Silver complexes of a novel tripodal N-heterocyclic carbene ligand: evidence for significant metal−carbene π-interaction. Organometallics 2003;22(4):612–4. https://doi.org/10.1021/om020935j.Search in Google Scholar
30. Rit, A, Pape, T, Hahn, FE. Self-assembly of molecular cylinders from polycarbene ligands and AgI or AuI. J Am Chem Soc 2010;132(13):4572–3. https://doi.org/10.1021/ja101490d.Search in Google Scholar PubMed
31. Hahn, FE, Radloff, C, Pape, T, Hepp, A. Synthesis of silver (I) and gold (I) complexes with cyclic tetra- and hexacarbene ligands. Chem Eur J 2008;14(35):10900–4. https://doi.org/10.1002/chem.200801877.Search in Google Scholar PubMed
32. Altmann, PJ, Weiss, DT, Jandl, C, Kühn, FE. Exploring coordination modes: late transition metal complexes with a methylene-bridged macrocyclic tetra-NHC ligand. Chem Asian J 2016;11(10):1597–1605. https://doi.org/10.1002/asia.201600198.Search in Google Scholar PubMed
33. Weiss, DT, Haslinger, S, Jandl, C, Pöthig, A, Cokoja, M, Kühn, FE. Application of Open Chain Tetraimidazolium Salts as Precursors for the Synthesis of Silver Tetra(NHC) Complexes. Inorg Chem 2015;54(2):415–7. https://doi.org/10.1021/ic502838x.Search in Google Scholar PubMed
34. Fatima, T, Haque, RA, Iqbal, MA, Razali, MR. A new approach for the synthesis of tetrabenzimidazolium salt as a precursor for the tetra-N-heterocyclic carbene dinuclear silver(I) complex. J Organomet Chem 2017;831:50–4. https://doi.org/10.1016/j.jorganchem.2016.12.028.Search in Google Scholar
35. Habib, A, Iqbal, MA, Bhatti, HN, Kamal, A, Kamal, S. Synthesis of alkyl/aryl linked binuclear silver(I)-N-Heterocyclic carbene complexes and evaluation of their antimicrobial, hemolytic and thrombolytic potential. Inorg Chem Commun 2020;111:107670. https://doi.org/10.1016/j.inoche.2019.107670.Search in Google Scholar
36. Yaqoob, M, Gul, S, Zubair, NF, Iqbal, J, Iqbal, MA. Theoretical calculation of selenium N-heterocyclic carbene compounds through DFT studies: Synthesis, characterization and biological potential. J Mol Struct 2020;1204:127462. https://doi.org/10.1016/j.molstruc.2019.127462.Search in Google Scholar
37. Habib, A, Iqbal, MA, Bhatti, HN. Polynuclear Ag(I)-N-heterocyclic carbene complexes: synthesis, electrochemical and in vitro anticancer study against human breast cancer and colon cancer. J Coord Chem 2019;72(12):2065–2079. https://doi.org/10.1080/00958972.2019.1632837.Search in Google Scholar
38. Citadelle, CA, Le Nouy, E, Bisaro, F, Slawin, AMZ, Cazin, CSJ. Simple and versatile synthesis of copper and silver N-heterocyclic carbene complexes in water or organic solvents. Dalton Trans 2010;39(19):4489–91. https://doi.org/10.1039/c0dt00128g.Search in Google Scholar PubMed
39. Wheatley, JE, Ohlin, CA, Chaplin, AB. Solvent promoted reversible cyclometalation in a tethered NHC iridium complex. Chem Comm 2014;50(6):685–7. https://doi.org/10.1039/c3cc48015a.Search in Google Scholar PubMed
40. Aresta, M, Quaranta, E. Role of the macrocyclic polyether in the synthesis of N-alkylcarbamate esters from primary amines, CO2 and alkyl halides in the presence of crown-ethers. Tetrahedron 1992;48(8):1515–30. https://doi.org/10.1016/s0040-4020(01)92239-2.Search in Google Scholar
41. Haque, RA, Iqbal, MA, Mohamad, F, Razali, MR. Antibacterial and DNA cleavage activity of carbonyl functionalized N-heterocyclic carbene-silver(I) and selenium Compounds. J Mole Struct 2018;1155:362–70. https://doi.org/10.1016/j.molstruc.2017.10.092.Search in Google Scholar
42. Haque, RA, Hasanudin, N, Hussein, MA, Ahamed, SA, Iqbal, MA. Bis-N-heterocyclic carbene silver (I) and palladium (II) complexes: efficient antiproliferative agents against breast cancer cells. Inorg Nano-Met Chem 2017;47(1):131–7. https://doi.org/10.1080/15533174.2016.1157816.Search in Google Scholar
43. Kamal, A, Nazari, M, Yaseen, M, Iqbal, MA, Ahamed, MBK, Majid, ASA, et al. Green synthesis of selenium-N-heterocyclic carbene compounds: evaluation of antimicrobial and anticancer potential. Bioorg Chem 2019;90:103042. https://doi.org/10.1016/j.bioorg.2019.103042.Search in Google Scholar PubMed
44. Amanullah, AU, Ali, U, Ans, M, Iqbal, J, Iqbal, MA, Shoaib, M. Benchmark study of benzamide derivatives and four novel theoretically designed (L1, L2, L3, and L4) ligands and evaluation of their biological properties by DFT approaches. J Mol Model 2019;25(8):223. https://doi.org/10.1007/s00894-019-4115-3.Search in Google Scholar PubMed
45. Yaqoob, M, Gul, S, Zubair, NF, Iqbal, J, Iqbal, MA. Theoretical calculation of selenium N-heterocyclic carbene compounds through DFT studies: synthesis, characterization and biological potential. J Mol Struct 2020;1204:127462. https://doi.org/10.1016/j.molstruc.2019.127462.Search in Google Scholar
46. Habib, A, Nazari, M, Iqbal, MA, Bhatti, HN, Ahmed, MBK, Majid, AMSA. Unsymmetrically substituted benzimidazolium based Silver (I)-N-heterocyclic carbene complexes: Synthesis, characterization and in vitro anticancer study against human breast cancer and colon cancer. J Saudi Chem Soc 2019;23(7):795–808. https://doi.org/10.1016/j.jscs.2019.03.002.Search in Google Scholar
47. Asif, M, Iqbal, MA, Hussein, MA, Oon, CE, Haque, RA, Khadeer Ahamed, MB, et al. Human colon cancer targeted pro-apoptotic, anti-metastatic and cytostatic effects of binuclear Silver(I)–N-Heterocyclic carbene (NHC) complexes. Eur J Med Chem 2016;108:177–87. https://doi.org/10.1016/j.ejmech.2015.11.034.Search in Google Scholar PubMed
48. Ali, S, Riaz, A, Majeed, MI, Iqbal, MA, Bhatti, HN, Rashid, N, et al. Raman spectroscopy along with principal component analysis for the confirmation of Silver(I)-N-heterocyclic carbene complex formation. Spectrochim Acta Part A: Mol Biomol Spectrosc 2019;228:117851. https://doi.org/10.1016/j.saa.2019.117851.Search in Google Scholar PubMed
49. Habib, A, Iqbal, MA, Bhatti, HN, Shahid, M. Effect of ring substitution on synthesis of benzimidazolium salts and their silver(I) complexes: characterization, electrochemical studies and evaluation of anticancer potential. Transit Met Chem 2019;44:431–43. https://doi.org/10.1007/s11243-019-00321-7.Search in Google Scholar
50. Goossens, K, Lava, K, Bielawski, CW, Binnemans, K. Ionic liquid crystals: versatile materials. Chem Rev 2016;116(8):4643–807. https://doi.org/10.1021/cr400334b.Search in Google Scholar PubMed
51. Tamri, P, Hemmati, A, Boroujerdnia, MG. Wound healing properties of quince seed mucilage: in vivo evaluation in rabbit full-thickness wound model. Int J Surg 2014;12(8):843–7. https://doi.org/10.1016/j.ijsu.2014.06.016.Search in Google Scholar PubMed
Supplementary material
The online version of this article offers supplementary material https://doi.org/10.1515/ZNC-2020-0069.
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