Synlett 2013; 24(19): 2519-2524
DOI: 10.1055/s-0033-1339545
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© Georg Thieme Verlag Stuttgart · New York

Is the Isodesmic Reaction Approach a Better Model for Accurate Calculation of pK a of Organic Superbases? A Computational Study

Abul Kalam Biswas
a  Computation and Simulation Unit (Analytical Discipline and Centralized Instrument Facility), CSIR-Central Salt & Marine Chemicals Research Institute, Bhavnagar, Gujarat, 364 002, India
b  Academy of Scientific and Innovative Research, CSIR-Central Salt & Marine Chemicals Research Institute, Bhavnagar, Gujarat, 364 002, India   Fax: +91(278)2567562   Email: ganguly@csmcri.org
,
Rabindranath Lo
a  Computation and Simulation Unit (Analytical Discipline and Centralized Instrument Facility), CSIR-Central Salt & Marine Chemicals Research Institute, Bhavnagar, Gujarat, 364 002, India
,
Bishwajit Ganguly*
a  Computation and Simulation Unit (Analytical Discipline and Centralized Instrument Facility), CSIR-Central Salt & Marine Chemicals Research Institute, Bhavnagar, Gujarat, 364 002, India
b  Academy of Scientific and Innovative Research, CSIR-Central Salt & Marine Chemicals Research Institute, Bhavnagar, Gujarat, 364 002, India   Fax: +91(278)2567562   Email: ganguly@csmcri.org
› Author Affiliations
Further Information

Publication History

Received: 16 July 2013

Accepted: 18 July 2013

Publication Date:
27 August 2013 (online)


Abstract

The acid-base dissociation constant (pK a) can be related to the solubility and binding of drugs. However, measuring accurate pK a values is a challenging task. In this study, we have examined the pK a of various organic superbases: naphthalenes, cyclic guanidines, vinamidines, and acyclic guanidines computationally. We have calculated the pK a of such superbases by employing two methods: a conventional thermodynamic cycle and a second method based on an isodesmic reaction. The thermodynamic cycle involves computation of solvation free energy by using gas-phase free energy and the difference in solvation free energies (∆Gsolv) between products and reactants. Calculations performed with the isodesmic reaction approach do not use the free energy of solvation; hence, the accuracy of the approach is less sensitive to solvent molecules and global charges of the calculated species. The root-mean-square errors (RMSE) predict that the pK a of the studied organic superbases are more accurate when calculated with the isodesmic reaction approach.

Supporting Information

 
  • References and Notes

    • 1a Alder RW. Chem. Rev. 1989; 89: 1215
    • 1b Alder RW. Tetrahedron 1990; 46: 683
  • 2 Llamas-Saiz AL, Foces-Foces C, Elguero J. J. Mol. Struct. 1994; 328: 297
  • 3 Staab HA, Saupe T. Angew. Chem., Int. Ed. Engl. 1988; 27: 865
  • 4 Raczyńska ED, Decouzon M, Gal J.-F, Maria P.-C, Gelbard G, Vielfaure-Joly J. J. Phys. Org. Chem. 2001; 14: 25
  • 5 Gal J.-F, Maria P.-C, Raczyńska ED. J. Mass Spectrom. 2001; 36: 699
  • 6 Alcami M, Mó O, Yáñez M. Mass Spectrom. Rev. 2001; 20: 195
  • 7 Alcami M, Mó O, Yáñez M. J. Phys. Org. Chem. 2002; 15: 174
    • 8a Raczyńska ED, Maria P.-C, Gal J.-F, Decouzon M. J. Phys. Org. Chem. 1994; 7: 725
    • 8b Howard ST, Platts JA, Coogan MP. J. Chem. Soc., Perkin Trans. 2 2002; 899
    • 9a Singh A, Chakraborty S, Ganguly B. Eur. J. Org. Chem. 2006; 4938
    • 9b Singh A, Ganguly B. Eur. J. Org. Chem. 2007; 420
    • 9c Singh A, Ganguly B. J. Phys. Chem. A 2007; 111: 6468
    • 9d Singh A, Ganguly B. New J. Chem. 2008; 32: 210
    • 10a Maksić ZB, Kovačević B. J. Org. Chem. 2000; 65: 3303
    • 10b Vianello R, Kovačević B, Maksić ZB. New J. Chem. 2002; 26: 1324
    • 10c Kovačević B, Maksić ZB. Chem. Eur. J. 2002; 8: 1694
    • 10d Margetic D, Ishikawa T, Kumamoto T. Eur. J. Org. Chem. 2010; 6563
    • 10e Coles MP, Aragón-Sàez PJ, Oakley SH, Hitchcock PB, Davidson MG, Maksić ZB, Vianello R, Leito I, Kaljurand I, Apperley DC. J. Am. Chem. Soc. 2009; 131: 16858
    • 10f Peran N, Maksić ZB. Chem. Commun. 2011; 47: 1327
  • 11 Koppel IA, Schwesinger R, Breuer T, Burk P, Herodes K, Koppel I, Leito I, Mishima M. J. Phys. Chem. A 2001; 105: 9575
    • 12a Maksić ZB. Kovačević B. J. Phys. Chem. A 1998; 102: 7324
    • 12b Maksić ZB, Glasovac Z, Despotović I. J. Phys. Org. Chem. 2002; 15: 499
    • 13a Lo R, Ganguly B. New J. Chem. 2011; 35: 2544
    • 13b Lo R, Ganguly B. Chem. Commun. 2012; 48: 5865
    • 13c Biswas AK, Lo R, Ganguly B. J. Phys. Chem. A 2013; 117: 3109
    • 13d Lo R, Singh A, Kesharwani MK, Ganguly B. Chem. Commun. 2012; 48: 5865
  • 14 Schwesinger R, Schlemper H, Hasenfratz C, Willaredt J, Dambacher T, Breuer T, Ottaway C, Fletschinger M, Boele J, Fritz M, Putzas D, Rotter HW, Bordewell FG, Satish AV, Ji G.-Z, Peters E.-M, Peters K, von Schnering HG, Walz L. Liebigs Ann. 1996; 1055
    • 15a Kovačević B, Barić D, Maksić ZB. New J. Chem. 2004; 28: 284
    • 15b Kovačević B, Maksić ZB. Tetrahedron Lett. 2006; 47: 2553
  • 16 Kovačević B, Maksić ZB. Chem. Commun. 2006; 1524
  • 17 Schwesinger R, Hasenfratz C, Schlemper H, Walz L, Peters E.-M, Peters K, von Schnering HG. Angew. Chem. Int. Ed. Engl. 1993; 32: 1362
  • 18 Bucher G. Angew. Chem. Int. Ed. 2003; 42: 4039
    • 19a Pahadi NK, Ube H, Terada M. Tetrahedron 2007; 48: 8700
    • 19b Grainger RS, Leadbeater NE, Pàmies AM. Catal. Commun. 2010; 3: 449
    • 20a Heldebrant DJ, Yonker CR, Jessop PG, Phan L. Energy Environ. Sci. 2008; 1: 487
    • 20b Lo R, Ganguly B. New J. Chem. 2012; 36: 2549
  • 21 Kakuchi T, Chen Y, Kitakado J, Mori K, Fuchise K, Satoh T. Macromolecules 2011; 44: 4641
  • 22 Kaljurand I, Rodima T, Leito I, Koppel IA, Schwesinger R. J. Org. Chem. 2000; 65: 6202
    • 24a Kapinos LE, Song B, Sigel H. Chem. Eur. J. 1999; 5: 1794
    • 24b Donkor KK, Kratochvil BJ. J. Chem. Eng. Data 1993; 38: 569
  • 25 Tables of Rate and Equilibrium Constants of Heterolytic Organic Reaction. Palm V. VINITI; Moscow-Tartu: 1975-1985
  • 26 Izutsu K IUPAC Chemical Data Series No. 35 Acid-Base Dissociation Constants in Dipolar Aprotic Solvents . Blackwell Scientific; Oxford: 1990
    • 27a Coetzee JF. Prog. Phys. Org. Chem. 1967; 4: 45 ; and references therein
    • 27b Magoński J, Rajer B. J. Chem. Soc., Perkin Trans. 2 2000; 1181
    • 28a Liptak MD, Shields GC. J. Am. Chem. Soc. 2001; 123: 7314
    • 28b Liptak MD, Gross KC, Seybold PG, Feldgus S, Shields GC. J. Am. Chem. Soc. 2002; 124: 6421
    • 28c Murlowska K, Sadlej-Sosnowska N. J. Phys. Chem. A 2005; 109: 5590
  • 29 Kovačević B, Maksić ZB. Org. Lett. 2001; 3: 1523
  • 30 Glasovac Z, Eckert-Maksić M, Maksić ZB. New J. Chem. 2009; 33: 588
  • 31 Casasnovas R, Fernández D, Casto JO, Frau J, Donoso J, Muňoz F. Theor. Chem. Acc. 2011; 130: 1
    • 32a Pozharskii AF. Russ. Chem. Rev. 1998; 67: 1
    • 32b Eckert-Maksić M, Glasovac Z, Trošelj P, Kütt A, Rodima T, Koppel I, Koppel IA. Eur. J. Org. Chem. 2008; 5176
    • 32c Schwesinger R, Miβfeldt M, Peters K, Schnering HG. V. Angew. Chem. Int. Ed. 1987; 26: 1165
    • 32d Superbases for Organic Synthesis . Ishikawa T. Wiley; Chichester, West Sussex: 2009
    • 33a Kelly CP, Cramer CJ, Truhlar DG. J. Chem. Theory Comput. 2005; 1: 1133
    • 33b Takano Y, Houk KN. J. Chem. Theory Comput. 2005; 1: 70
  • 34 Alder RW, Bowman PS, Steele WR, Winterman DP. Chem. Commun. 1968; 723
    • 35a Diem MJ, Burow DF, Fry JL. J. Org. Chem. 1977; 42: 1801
    • 35b Ho TL, Wong CM. Synth. Commun. 1975; 5: 87
    • 35c Alper H, Wolin MS. J. Org. Chem. 1975; 40: 437
    • 36a Simoni D, Rondanin R, Morini M. Tetrahedron Lett. 2000; 41: 1607
    • 36b Reddy MV. N, Kumar BS, Balakrishna A, Reddy CS, Nayak SK, Reddy CD. ARKIVOC 2007; (xv): 46
  • 37 Radić N, Maksić ZB. J. Phys. Org. Chem. 2012; 25: 1168
  • 38 Hernandez-Laguna A, Aboud J.-LM, Homan H, Lopez-Mardomingo C, Notario R, Cruz-Rodriguez Z, Haro-Ruiz MD, Bottella V. J. Phys. Chem. 1995; 99: 9087
  • 39 Raczyńska E, Cyrański MK, Gutowski M, Rak J, Gal JF, Maria PC, Darowska M, Duczmal K. J. Phys. Org. Chem. 2003; 16: 91
  • 40 Schlippe YV. G, Hedstrom L. Arch. Biochem. Biophys. 2005; 433: 266
  • 41 Kovačević B, Glasovac Z, Maksić ZB. J. Phys. Org. Chem. 2002; 15: 765