Diazoxide and its Tautomers - A DFT Treatment
Abstract
Diazoxide have several potential effectors that may potentially contribute to cardio protection. It is used to manage symptoms of hypoglycemia that is caused by pancreas cancer, surgery, or other conditions. It also acts as a non-diuretic antihypertensive agent. Diazoxide possessing various tautomeric forms should display variable biological properties depending on its tautomer content. It may exhibit 1,3- and 1,5-type proton tautomerism. Presently, all those possible tautomeric forms are considered. All the calculations have been performed within the realm of density functional theory with the constraints of B3LYP/6-311++G(d,p) level. All the tautomers are electronically stable and thermo chemically favorable formation values at the standard conditions. Some quantum chemical and spectral properties of those tautomeric systems as well as nucleus-independent chemical shift (NICS) values have been obtained and discussed.
References
Benowitz, N.L., & Bourne, H.R. (1984). Antihypertensive agents. In Basic and clinical pharmacology. (Katzung, B.G. Ed.). Los Altros, California: Lange Medical Pub.
Orita, Y., Ando, A., Takamitsu, Y., Shirai, D., & Urakabe, S. (1972). Studies on Hückel’s molecular orbital calculation (3d-2p) of the sulfamyl part of thiazide diuretics. Jpn. Circ. J., 36(2), 187-190. https://doi.org/10.1253/jcj.36.187
Diazoxide, https://pubchem.ncbi.nlm.nih.gov
Wohl, A.J., Hausler, L.M., & Roth, F.E. (1967). Studies on the mechanism of antihypertensive action of diazoxide: ın vıtro vascular pharmacodynamıcs. Journal of Pharmacology and Experimental Therapeutics, 158(3), 531-539.
Staquet, M., Yabo, R., & Wolff, J.F. (1965). An adrenergic mechanism for hyperglycemia induced by diazoxide, Methabolism (Clinical and Experimental), 14(9), 1000-1009. https://doi.org/10.1016/0026-0495(65)90116-2
Timlin, M., Black, A.B., Delaney, H.M., Matos, R.I., & Percival, C.S. (2017). Development of pulmonary hypertension during treatment with diazoxide: a case series and literature review. Pediatr. Cardiol., 38, 1247-1250. https://doi.org/10.1007/s00246-017-1652-3
Anastacio, M.M., Kanter, E.M., Makepeace, C., Keith, A.D., Zhang, H., Schuessler, R.B., Nichols, C.G., & Lawton, J.S. (2013). Cardioprotective mechanism of diazoxide involves the inhibition of succinate dehydrogenase. The Annals of Thoracic Surgery, 95(6), 2042-2050. https://doi.org/10.1016/j.athoracsur.2013.03.035
Schäfer, G., Portenhauser, R., & Trolp, R. (1971). Inhibition of mitochondrial metabolism by the diabetogenic thiadiazine diazoxide—I: Action on succinate dehydrogenase and tca-cycle oxidations. Biochemical Pharmacology, 20(6), 1271-1280. https://doi.org/10.1016/0006-2952(71)90358-3
Sellitto, A.D., Maffit, S.K., Al-Dadah, A.S., Zhang, H., Schuessler, R.B., Nichols, C.G., & Lawton, J.S. (2010). Diazoxide maintenance of myocyte volume and contractility during stress: evidence for a non-sarcolemmal KATP channel location. J. Thorac. Cardiovasc. Surg., 140(5), 11531159. https://doi.org/10.1016/j.jtcvs.2010.07.047
Mizutani, S., Al-Dadah, A.S., Bloch, J.B., Prasad, S.M., Diodato, M.D., Schuessler. R.B., Damiano, R.J., Jr., & Lawton, J.S. (2006). Hyperkalemic cardioplegia-induced myocyte swelling and contractile dysfunction: prevention by diazoxide. Ann. Thorac. Surg., 81(1), 154-9. https://doi.org/10.1016/j.athoracsur.2005.06.057
Al-Dadah, A.S., Voeller, R.K., Schuessler, R.B., Damiano, R.J. Jr., & Lawton, J.S. (2007). Maintenance of myocyte volume homeostasis during stress by diazoxide is cardioprotective. Ann. Thorac. Surg., 84(3), 857-62. https://doi.org/10.1016/j.athoracsur.2007.04.103
Maffit, S.K., Sellitto, A.D., Al-Dadah, A.S., Schuessler, R.B., Damiano, R.J. Jr., & Lawton, J.S. (2012). Diazoxide maintains human myocyte volume homeostasis during stress. J. Am. Heart Assoc., 1(2), e000778. https://doi.org/10.1161/jaha.112.000778
Garlid, K.D., Paucek, P., Yarov-Yarovoy, V., Murray, H.N., Darbenzio, R.B., D’Alonzo, A.J., Lodge, N.J., Smith, M.A., & Grover, G.J. (1997). Cardioprotective effect of diazoxide and its interaction with mitochondrial ATP-sensitive K+ channels. Possible mechanism of cardioprotection. Circ. Res., 81(6), 1072-82. https://doi.org/10.1161/01.res.81.6.1072
Das, M., Parker, J.E., & Halestrap, A.P. (2003). Matrix volume measurements challenge the existence of diazoxide/glibenclamide-sensitive KATP channels in rat mitochondria. J. Physiol., 547(3), 893-902. https://doi.org/10.1113/jphysiol.2002.035006
D’hahan, N., Moreau, C., Prost, A.L., Jacquet, H., Alekseev, A.E., Terzic, A., & Vivaudou, M. (1999). Pharmacological plasticity of cardiac ATP-sensitive potassium channels toward diazoxide revealed by ADP. Proc. Natl. Acad. Sci., 96(21), 12162- 12167. https://doi.org/10.1073/pnas.96.21.12162
Lim, K.H., Javadov, S.A., Das, M., Clarke, S.J., Suleiman, M., & Halestrap, A.P. (2002). The effects of ischaemic preconditioning, diazoxide and 5-hydroxydecanoate on rat heart mitochondrial volume and respiration. J. Physiol., 545(3), 961-974. https://doi.org/10.1113/jphysiol.2002.031484
Graber, A.L., Porte, D. Jr., & Williams, R.H. (1966). Clinical use of diazoxide and mechanism for its hyperglycemic effects. Diabetes, 15(3), 143-148. https://doi.org/10.2337/diab.15.3.143
Coetzee, W.A. (2013). Multiplicity of effectors of the cardioprotective agent, diazoxide. Pharmacol. Ther., 140(2), 167-175. https://doi.org/10.1016/j.pharmthera.2013.06.007
Reutov, O. (1970). Theoretical principles of organic chemistry, Moscow: Mir Pub.
Anslyn, E.V., & Dougherty, D.A. (2006). Modern physical organic chemistry, Sausalito, California: University Science Books.
Dupont, L., Pirotte, B., de Tullio, P., Masereel, B., & Delarge, J. (1995). Les activateurs de canaux potassiques: étude structurale comparative du pinacidil, du diazoxide et du cromakalim [Potassium channel activators: comparative structural study of pinacidil, diazoxide and cromakalim]. Ann Pharm Fr., 53(5), 201-8. https://doi.org/10.1107/s0108767378095744
Bandoli, G., & Nicolini, M. (1977). Crystal and molecular structure of diazoxide, an antihypertensive agent. Journal of Crystal and Molecular Structure, 7, 229-240. https://doi.org/10.1007/BF01218380
Kamal, A., Khan, M.N.A., Reddy, K.S., Rohini, K., Sastry, G.N., Sateesh, B., & Sridhar, B. (2007). Synthesis, structure analysis, and antibacterial activity of some novel 10- substituted 2-(4-piperidyl/phenyl)-5,5-dioxo[1,2,4]triazolo[1,5-b][1,2,4]benzothiadiazine derivatives. Bioorganic & Medicinal Chemistry Letters, 17(19), 5400-5405. https://doi.org/10.1016/j.bmcl.2007.07.043
Stewart, J.J.P. (1989). Optimization of parameters for semi empirical methods I. J. Comput. Chem., 10, 209-220. https://doi.org/10.1002/jcc.540100208
Stewart, J.J.P. (1989). Optimization of parameters for semi empirical methods II. J. Comput. Chem., 10, 221-264. https://doi.org/10.1002/jcc.540100209
Leach, A.R. (1997). Molecular modeling. Essex: Longman.
Kohn, W., & Sham, L.J. (1965). Self-consistent equations including exchange and correlation effects. Phys. Rev., 140, 1133-1138. https://doi.org/10.1103/PhysRev.140.A1133
Parr, R.G., & Yang, W. (1989). Density functional theory of atoms and molecules. London: Oxford University Press.
Becke, A.D. (1988). Density-functional exchange-energy approximation with correct asymptotic behavior. Phys. Rev. A, 38, 3098-3100. https://doi.org/10.1103/PhysRevA.38.3098
Vosko, S.H., Wilk, L., & Nusair, M. (1980). Accurate spin-dependent electron liquid correlation energies for local spin density calculations: a critical analysis. Can. J. Phys., 58, 1200-1211. https://doi.org/10.1139/p80-159
Lee, C., Yang, W., & Parr, R.G. (1988). Development of the Colle-Salvetti correlation energy formula into a functional of the electron density. Phys. Rev. B, 37, 785-789. https://doi.org/10.1103/PhysRevB. 37.785
SPARTAN 06 (2006). Wavefunction Inc. Irvine CA, USA.
Gaussian 03, Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Montgomery, Jr., J.A., Vreven, T., Kudin, K.N., Burant, J.C., Millam, J.M., Iyengar, S.S., Tomasi, J., Barone, V., Mennucci, B., Cossi, M., Scalmani, G., Rega, N., Petersson, G.A., Nakatsuji, H., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Klene, M., Li, X., Knox, J.E., Hratchian, H.P., Cross, J.B., Bakken, V., Adamo, C., Jaramillo, J., Gomperts, R., Stratmann, R.E., Yazyev, O., Austin, A.J., Cammi, R., Pomelli, C., Ochterski, J.W., Ayala, P.Y., Morokuma, K., Voth, G.A., Salvador, P., Dannenberg, J.J., Zakrzewski, V.G., Dapprich, S., Daniels, A.D., Strain, M.C., Farkas, O., Malick, D.K., Rabuck, A.D., Raghavachari, K., Foresman, J.B., Ortiz, J.V., Cui, Q., Baboul, A.G., Clifford, S., Cioslowski, J., Stefanov, B.B., Liu, G., Liashenko, A., Piskorz, P., Komaromi, I., Martin, R.L., Fox, D.J., Keith, T., Al-Laham, M.A., Peng, C.Y., Nanayakkara, A., Challacombe, M., Gill, P.M.W., Johnson, B., Chen, W., Wong, M.W., Gonzalez, C., & Pople, J.A., Gaussian, Inc., Wallingford CT, 2004.
Bouider, N., Fhayli, W., Ghandour, Z., Boyer, M., Harrouche, K., Florence, X., Pirotte, B., Lebrun, P., Faury, G., & Khelili, S. (2015). Design and synthesis of new potassium channel activators derived from the ring opening of diazoxide: Study of their vasodilatory effect, stimulation of elastin synthesis and inhibitory effect on insulin release. Bioorganic and Medicinal Chemistry, 23, 1735-1746. http://doi.org/10.1016/j.bmc.2015.02.043
Minkin, V.I., Glukhovtsev, M.N., & Simkin, B.Y. (1994). Aromaticity and antiaromaticity: Electronic and structural aspects. New York: Wiley.
Schleyer, P.R., & Jiao, H. (1996). What is aromaticity?. Pure Appl. Chem., 68, 209-218. https://doi.org/10.1351/pac199668020209
Glukhovtsev, M.N. (1997). Aromaticity today: energetic and structural criteria. J. Chem. Educ., 74, 132-136. https://doi.org/10.1021/ed074p132
Krygowski, T.M., Cyranski, M.K., Czarnocki, Z., Hafelinger, G., & Katritzky, A.R. (2000). Aromaticity: a theoretical concept of immense practical importance. Tetrahedron, 56, 1783-1796. https://doi.org/10.1016/S0040-4020(99)00979-5
Schleyer, P.R. (2001). Introduction: aromaticity. Chem. Rev., 101, 1115-1118. https://doi.org/10.1021/cr0103221
Cyranski, M.K., Krygowski, T.M., Katritzky, A.R., & Schleyer, P.R. (2002). To what extent can aromaticity be defined uniquely?. J. Org. Chem., 67, 1333-1338. https://doi.org/10.1021/jo016255s
Chen, Z., Wannere, C.S., Corminboeuf, C., Puchta, R., & Schleyer, P. von R. (2005). Nucleus independent chemical shifts (NICS) as an aromaticity criterion. Chem. Rev., 105(10), 3842-3888. https://doi.org/10.1021/cr030088
Gershoni-Poranne, R., & Stanger, A. (2015). Magnetic criteria of aromaticity. Chem. Soc. Rev., 44(18), 6597-6615. https://doi.org/10.1039/C5CS00114E
Dickens, T.K., & Mallion, R.B. (2016). Topological ring-currents in conjugated systems. MATCH Commun. Math. Comput. Chem., 76, 297-356.
Stanger, A. (2010). Obtaining relative induced ring currents quantitatively from NICS. J. Org. Chem., 75(7), 2281-2288. https://doi.org/10.1021/jo1000753
Monajjemi, M., & Mohammadian, N.T. (2015). S-NICS: An aromaticity criterion for nano molecules. J. Comput. Theor. Nanosci., 12(11), 4895-4914. https://doi.org/10.1166/jctn.2015.4458
Schleyer, P.R., Maerker, C., Dransfeld, A., Jiao, H., & Hommes, N.J.R.E. (1996). Nucleus independent chemical shifts: a simple and efficient aromaticity probe. J. Am. Chem. Soc., 118, 6317-6318. https://doi.org/10.1021/ja960582d
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