The amidine formed by tacrine and saccharin revisited: An ab initio Investigation of Structural, Electronic and Spectroscopic Properties

Abstract

Computational study of tacrine and saccharin and their amidine complex (TacSac) was peformed by ab initio calculations including electron correlation. Structure, UV-Vis spectra and charge distribution of the amidine (TacSac) were investigated using ground state geometries optimized at MP2/6-311++G(d,p) level. The effects of solvent was investigated using polarizable continuum model (PCM) in conjunction with the solvation model based on density (SMD) approach. TacSac geometry remained same in gas phase and in H₂O both with PCM and SMD models in contrast to former DFT results. The amidine is calculated to be stable indicating that former DFT calculations underestimated the stability of the investigated amidine. UV-Vis spectra and electronic transitions were calculated at CIS/6-311++G(d,p), B3LYP/6-311++G(d,p) and CAM-B3LYP/6-311++G(d,p) levels of theory and B3LYP gave the best results. TacSac has a peak at a higher wavelength enabling S₀→S₁ transition with a lower energy. S₀→S₁ transition corresponds to full charge transfer between HOMO and LUMO orbitals of TacSac in H₂O. The ab initio results indicate that the TacSac system can be synthesized with an easy condensation reaction, and that the amidine product is a potential candidate for photochemical charge-transfer systems.

Keywords

• Amidine,Møller-Plesset,Density Functional Theory,Tacrine,Saccharin

References

1. [1] S. E. Freeman, R. M. Dawson, Tacrine: a pharmacological review, Prog Neurobiol 36 (1991) 257–277.
2. [2] V. Tumiatti, A. Minarini, M. L. Bolognesi, A. Milelli, M. Rosini, C. Melchiorre, Tacrine derivatives and Alzheimer’s disease. Curr Med Chem 17 (2010) 1825–1838. [3] A. Alberti, The chemical and biological properties of acridines. Sci Prog 37 (1949) 418–434.
3. [4] F. H. Shaw, G. A. Bentley, The pharmacology of some new anticholinesterases, Aust J Exp Biol Med Sci 31 (1953) 573–576.
4. [5] P. N. Kaul, Enzyme inhibiting action of tetrahydroaminoacridine and its structural fragments, J Pharm Pharmacol 14 (1962) 243–248.
5. [6] W. K. Summers, L. V. Majovski, G. M. Marsh, K. Tachiki, A. Kling, Oral tetrahydroaminoacridine in long-term treatment of senile dementia, Alzheimer type, N Engl J Med 315 (1986) 1241–1245.
6. [7] W. K. Summers, Tacrine, and Alzheimer's treatments, J Alzheimers Dis 9 (2006) 439–445.
7. [8] M. Harel, I. Schalk, L. Ehret-Sabatier, F. Bouet, M. Goeldner, C. Hirth, P. H. Axelsen, I. Silman, J. L. Sussman, Quaternary ligand binding to aromatic residues in the active-site gorge of acetylcholinesterase, Proceedings of the National Academy of Sciences USA 90 (1993) 9031–9035.
8. [9] L. Pishkar, P. R. Jamaat, S. Makarem, Theoretical study of structure spectral properties of tacrine as Alzheimer drug, J Phys Theor Chem IAU Iran 12(1) (2015) 69–75

9. [10] K. Y. Wong, A. G. Mercader, L. M. Saavedra, B. Honarparvar, G. P. Romanelli, P. R. Duchowicz, QSAR analysis on tacrine-related acetylcholinesterase inhibitors, Journal of Biomedical Science 21 (2014) 84.
10. [11] É. C. M. Nascimento, J. B. L. Martins, M. L. dos Santos, R. Gargano, Theoretical study of classical acetylcholinesterase inhibitors, Chemical Physics Letters 458 (2008) 285–289.
11. [12] M. A. R. Matos, M. S. Miranda, V. M. F. Morais, J. F. Liebman, Saccharin: a combined experimental and computational thermochemical investigation of a sweetener and sulfonamide, Molecular Physics 103(2–3) (2005) 221–228.
12. [13] R. Kant, Sweet proteins-potential replacement for artificial low calorie sweeteners, Nutrition Journal 4 (2004) 5.
13. [14] M. R. Weihrauch, V. Diehl, H. Bohlen, Artificial sweeteners-are they potentially carcinogenic?, Med Klin (Munich) 96 (2002) 670–675.
14. [15] R. B. Kanarek, Does sucrose or aspartame cause hyperactivity in children?, Nutr Rev 52 (1994) 173–175.
15. [16] S. Cohen, What's the truth about the health risks of sugar substitutes such as saccharin and aspartame?, Health News 7(1) (2001) 10.
16. [17] L. O. Nabors, Saccharin and aspartame: are they safe to consume during pregnancy?, The Journal of Reproductive Medicine 33 (1988) 102.
17. [18] A. Hagiwara, S. Fukushima, M. Kitaori, M. Shibata, N. Ito, Effects of three sweeteners on rat urinary bladder carcinogenesis initiated by N-butyl-N-(4-hydroxybutyl)-nitrosamine, Gann 75 (1984) 763–768.
18. [19] A. Brizuela, E. Romano, A. Yurquina, S. Locatelli, S. A. Brandan, Experimental and theoretical vibrational investigation on the saccharinate ion in aqueous solution, Spectrochimica Acta A 95 (2012) 399–406.
19. [20] V. D. Filimonov, E. A. Krasnokutskay, O. K. Poleshchuk, Yu A. Lesina, V. K. Chaikovskii, Electronic structures and reactivities of iodinating agents in the gas phase and in solutions: a density functional study, Russ Chem B+ 55(8) (2006) 1328–1336.
20. [21] M. M. Branda, N. J. Castellani, S. H. Tarulli, O. V. Quinzani, E. J. Baran, R. H. Contreras, DFTstudy of electronic structure of saccharin, thiosaccharin, and their respective ıons: effects of metal coordination on thiosaccharinate electronic structure. International Journal of Quantum Chemistry 89 (2002) 525–534.
21. [22] M. Remko, Theoretical study of molecular structure and gas phase acidity of some biologically active sulfonamides, The Journal of Physical Chemistry A 107 (2003) 720–725.
22. [23] J. Y. Quek, T. P. Davis, A. B. Lowe, Amidine functionality as a stimulus-responsive building block, Chemical Society Reviews 42 (2013) 7326-7334.
23. [24] T. Ishikawa, in Superbases for Organic Synthesis: Guanidines, Amidines, Phosphazenes and Related Organocatalysts, ed. T. Ishikawa, John Wiley & Sons, Ltd, 2009, pp. 1–6.
24. [25] T. I. a. T. Kumamoto, in Superbases for Organic Synthesis: Guanidines, Amidines, Phosphazenes and Related Organocatalysts, ed. T. Ishikawa, JohnWiley & Sons, Ltd, 2009, pp. 49–86.
25. [26] A. A. Aly, A. M. Nour-El-Din, Functionality of amidines and amidrazones, ARKIVOC I (2008) 153–194.
26. [27] S. Maddaford, S. C. Annedi, J. Ramnauth, S. Rakhit, Advancements in the development of nitric oxide synthase inhibitors, Annu. Rep. Med. Chem. 44 (2009) 27-50.
27. [28] C. Maccallini, M. Fantacuzzi, R. Amoroso, Amidine-Based Bioactive Compounds for the Regulation of Arginine Metabolism, Mini Reviews in Medicinal Chemistry 13 (2013) 1305-1310.
28. [29] R. L. Shriner, F. W. Neumann, The chemistry of the amidines, Chemical Reviews 35 (1944) 351–425.
29. [30] E. D. Raczyńska, M. Makowski, M. Hallmann, B. Kamińska, Geometric and energetic consequences of prototropy for adenine and its structural model-a review, RSC Advances 5 (2015) 36587–36604.
30. [31] P. S. Lobanov, D. V. Dar'in, Acetamidines and acetamidoximes containing an electron-withdrawing group at the α-carbon atom: their use in the synthesis of nitrogen heterocycles, Chem Heterocycl Compd 49(4) (2013) 507–528.
31. [32] J. Nowicki, M. Muszyński, J-P. Mikkola, Ionic liquids derived from organosuperbases: en route to superionic liquids, RSC Advances 6 (2016) 9194–9208.
32. [33] M. N. C. Soeiro, K. Werbovetz, D. W. Boykin, W. D. Wilson, M. Z. Wang, A. Hemphill, Novel amidines and analogues as promising agents against intracellular parasites: a systematic review, Parasitology 140 (2013) 929–951.
33. [34] R. A. Michelin, P. Sgarbossa, S. Mazzega Sbovata, V. Gandin, C. Marzano, R. Bertani, Chemistry and biological activity of platinum amidine complexes, ChemMedChem 6 (2011) 1172–1183.
34. [35] V. T. Mathad, P. V. Solanki, V. Pavankumar, S. B. Uppelli, G. G. Sarode, A process for preparation of dabigatran etexilate mesylate and intermediates thereof,PCT Int. Appl. (2015), WO 2015128875 A2 Sep 03, 2015.
35. [36] J. E. Taylor, S. D. Bull, J. M. J. Williams, Amidines, isothioureas, and guanidines as nucleophilic catalysts, Chemical Society Reviews 41 (2012) 2109–2121.
36. [37] J. W. Liebeschuetz, R. B. Katz, A. D. Duriatti, M. L. Arnold, Rationally designed guanidine and amidine fungicides, Pestic Sci 50 (1997) 258–274.
37. [38] G. Wulff, R. Schönfeld, Polymerizable amidines—adhesion mediators and binding sites for molecular imprinting, Adv Mater 10(12) (1998) 957–959.
38. [39] G. Kantin, M. Krasavin, N-arylation of amidines and guanidines: an update, Current Organic Chemistry 20(13) (2016) 1370-1388.
39. [40] N. Acar, C. Selçuki, E. Coşkun, DFT and TDDFT investigation of the Schiff base formed by tacrine and saccharin, Journal of Molecular Modeling 23 (2017) 17.
40. [41] R. D. Dennington II, T. A. Keith, J. M. Millam, GaussView 5.0.9, Wallingford, CT, (2009)
41. [42] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, J. A. Montgomery Jr., J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Kobayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D. Daniels, Ö. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski, D. J. Fox, Gaussian 09, Revision C.01, Gaussian, Inc., Wallingford CT (2009).
42. [43] M. J. Frisch, M. Head-Gordon, J. A. Pople, A direct MP2 gradient method, Chemical Physics Letters 166 (1990) 275-280.
43. [44] M. Head-Gordon, J. A. Pople, M. J. Frisch, MP2 energy evaluation by direct methods, Chemical Physics Letters 153 (1988) 503-506.
44. [45] W. J. Hehre, L. Radom, P. V. Schleyer, J. A. Pople, Ab Initio Molecular Orbital Theory, John Wiley & Sons, New York, USA, 1986, 576.
45. [46] J. B. Foresman, M. Head-Gordon, J. A. Pople, and M. J. Frisch, Toward a Systematic Molecular Orbital Theory for Excited States, The Journal of Physical Chemistry 96 (1992) 135-149.
46. [47] A. D. Becke, Density‐functional thermochemistry. III. The role of exact exchange, The Journal of Chemical Physics 98 (1993) 5648-5652.
47. [48] C. Lee, W. Yang, R. G. Parr, Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density, Physical Review B 37 (1988) 785-789.
48. [49] T. Yanai, D. Tew, N. Handy, A new hybrid exchange-correlation functional using the Coulomb-attenuating method (CAM-B3LYP), Chemical Physics Letters 393 (2004) 51–57.
49. [50] J. Tomasi, B. Mennucci, E. Cancès, The IEF version of the PCM solvation method: an overview of a new method addressed to study molecular solutes at the QM ab initio level, Journal of Molecular Structure THEOCHEM 464 (1999) 211–226.
50. [51] J. Tomasi, B. Mennucci, R. Cammi, Quantum mechanical continuum solvation models, Chemical Reviews 105 (2005) 2999–3093.
51. [52] A. V. Marenich, C. J. Cramer, D. G. Truhlar, Universal solvation model based on solute electron density and on a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions, The Journal of Physical Chemistry B 113 (2009) 6378–6396.
52. [53] J. Cioslowski, A new population analysis based on atomic polar tensors, Journal of American Chemical Society 111(22) (1989) 8333–8336.