Skip to main content
SpringerLink
Log in

Hydration of Fluorobenzenes: A Molecular Dynamics Simulation Investigation

  • Review Article
  • Published:
Journal of the Indian Institute of Science Aims and scope

Abstract

Molecular dynamics simulations of benzene and 12 fluorobenzenes with various degrees of fluorine substitution in water reveal that the accumulation of water in the first solvent shell decreases with increase in number of fluorine atoms relative to benzene, with an exception of hexafluorobenzene. Further, the solute–solute radial density function indicates that partially substituted fluorobenzenes sample \( \uppi \)-stacked and T-shaped geometries. In contrast benzene and hexafluorobenzene sample only the T-shaped geometries. Comparison of solute–solute and solute–solvent radial density functions suggests that solute–solute interactions is preferred over solute–solvent interaction, which suggests the hydrophobic nature of fluorobenzenes, which increases with increase in number of fluorine atoms on the phenyl ring. The spatial distribution of water around the fluorobenzenes suggests that water avoids the C–F bond group, which indicates increase in hydrophobicity of fluorobenzenes with number of fluorine atoms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1:
Figure 2:
Figure 3:
Figure 4:
Figure 5:
Figure 6:
Figure 7:

Similar content being viewed by others

References

  1. Dikundwar AG, Sathishkumar R, Row TNG, Desiraju GR (2011) Structural variability in the monofluoroethynylbenzenes mediated through interactions involving ‘organic’ fluorine. Cryst Growth Des 11:3954–3963

    Article  CAS  Google Scholar 

  2. Thalladi VR, Weiss HC, Bläser D, Boese R, Nangia A, Desiraju GR (1998) C–H···F interactions in the crystal structures of some fluorobenzenes. J Am Chem Soc 120:8702–8710

    Article  CAS  Google Scholar 

  3. Dunitz JD, Schweizer WB (2006) Molecular pair analysis: C–H···F interactions in the crystal structure of fluorobenzene? And related matters. Chem A Eur J 12:6804–6815

    Article  CAS  Google Scholar 

  4. Dunitz JD, Taylor R (1997) Organic fluorine hardly ever accepts hydrogen bonds. Chem Eur J 3:89–98

    Article  CAS  Google Scholar 

  5. Shimonia L, Glusker JP (2015) The geometry of intermolecular interactions in some crystalline fluorine-containing organic compounds. Sci Cryst Struct Highlights Crystallogr 5:187–203

    Article  Google Scholar 

  6. Rosenberg RE (2018) The strength of hydrogen bonds between fluoro-organics and alcohols, a theoretical study. J Phys Chem A 122:4521–4529

    Article  CAS  Google Scholar 

  7. Biswas B, Mondal S, Singh PC (2017) Combined molecular dynamics, atoms in molecules, and ir studies of the bulk monofluoroethanol and bulk ethanol to understand the role of organic fluorine in the hydrogen bond network. J Phys Chem A 121:1250–1260

    Article  CAS  Google Scholar 

  8. Dalvit C, Vulpetti A (2016) Weak intermolecular hydrogen bonds with fluorine: detection and implications for enzymatic/chemical reactions, chemical properties, and ligand/protein fluorine nmr screening. Chem A Eur J 22:7592–7601

    Article  CAS  Google Scholar 

  9. Champagne PA, Desroches J, Paquin JF (2015) Organic fluorine as a hydrogen-bond acceptor: recent examples and applications. Synthesis 47:306–322

    CAS  Google Scholar 

  10. Gerling UIM, Salwiczek M, Cadicamo CD, Erdbrink H, Czekelius C, Grage SL, Wadhwani P, Ulrich AS, Behrends M, Haufe G, Koksch B (2015) Fluorinated amino acids in amyloid formation: a symphony of size, hydrophobicity and α-helix propensity. Chem Sci 5:819–830

    Article  Google Scholar 

  11. Buer BC, Meagher JL, Stuckey JA, Marsh ENG (2012) Structural basis for the enhanced stability of highly fluorinated proteins. Proc Natl Acad Sci 109:4810–4815

    Article  Google Scholar 

  12. Robalo JR, Verde AV (2019) Unexpected trends in the hydrophobicity of fluorinated amino acids reflect competing changes in polarity and conformation. Phys Chem Chem Phys 21:2029–2038

    Article  CAS  Google Scholar 

  13. Wilcken R, Zimmermann MO, Lange A, Joerger AC, Boeckler FM (2013) Principles and applications of halogen bonding in medicinal chemistry and chemical biology. J Med Chem 56:1363–1388

    Article  CAS  Google Scholar 

  14. Müller K, Faeh C, Diederich F (2007) Fluorine in pharmaceuticals: looking beyond intuition. Science 317:1881–1886

    Article  CAS  Google Scholar 

  15. Hagmann WK (2008) The many roles for fluorine in medicinal chemistry. J Med Chem 51:4359–5369

    Article  CAS  Google Scholar 

  16. Gutowsky HS, Emilsson T, Arunan E (1993) Low-J rotational spectra, internal rotation, and structures of several benzene–water dimers. J Chem Phys 99:4883–4893

    Article  CAS  Google Scholar 

  17. Suzuki S, Green PG, Bumgarner RE, Dasgupta S, Goddard WA, Blake GA (1992) Benzene forms hydrogen bonds with water. Science 257:942–945

    Article  CAS  Google Scholar 

  18. Evangelisti L, Brendel K, Mäder H, Caminati W, Melandri S (2017) Rotational spectroscopy probes water flipping by full fluorination of benzene. Angew Chemie 129:13887–13891

    Article  Google Scholar 

  19. Allesch M, Lightstone FC, Schwegler E, Galli G (2008) First principles and classical molecular dynamics simulations of solvated benzene. J Chem Phys 128:014501

    Article  CAS  Google Scholar 

  20. Tarakeshwar P, Kim KS, Brutschy B (1999) Fluorobenzene–water and difluorobenzene–water systems: an ab initio investigation. J Chem Phys 110:8501–8512

    Article  CAS  Google Scholar 

  21. Lau EY, Gerig JT, Barbara S (1996) Solvent effects on fluorine shielding in fluorobenzene. J Am Chem Soc 118:1194–1200

    Article  CAS  Google Scholar 

  22. Hernández-Trujillo J, Vela A (1996) Molecular quadrupole moments for the series of fluoro- and chloro-benzenes. J Phys Chem 100:6524–6530

    Article  Google Scholar 

  23. Van Der Spoel D, Lindahl E, Hess B, Groenhof G, Mark AE, Berendsen HJC (2005) GROMACS: fast, flexible, and free. J Comput Chem 26:1701–1718

    Article  CAS  Google Scholar 

  24. Jorgensen WL, Maxwell DS, Tirado-Rives J (1996) Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. J Am Chem Soc 118:11225–11236

    Article  CAS  Google Scholar 

  25. Shimizu K, Gomes MFC, Padua AAH, Rebelo LPN, Lopes JNC (2009) On the role of the dipole and quadrupole moments of aromatic compounds in the solvation by ionic liquids. J Phys Chem B 113:9894–9900

    Article  CAS  Google Scholar 

  26. Van Der Spoel D, Van Maaren PJ (2006) The origin of layer structure artifacts in simulations of liquid water. J Chem Theory Comput 2:1–11

    Article  CAS  Google Scholar 

  27. Petrova SS, Solovev AD (1997) The origin of the method of steepest descent. Hist Math 24:361–375

    Article  Google Scholar 

  28. Woodcock LV (1971) Isothermal molecular dynamics calculations for liquid salts. Chem Phys Lett 10:257–261

    Article  CAS  Google Scholar 

  29. Berendsen HJC, Postma JPM, Van Gunsteren WF, Dinola A, Haak JR (1984) Molecular dynamics with coupling to an external bath. J Chem Phys 81:3684–3690

    Article  CAS  Google Scholar 

  30. Feller SE, Zhang Y, Pastor RW, Brooks BR (1995) Constant pressure molecular dynamics simulation: the Langevin piston method. J Chem Phys 103:4613–4621

    Article  CAS  Google Scholar 

  31. Allen MP, Tildesley DJ (2017) Computer simulation of liquid, 2nd edn. Oxford University Press, Oxford

    Book  Google Scholar 

  32. Darden T, York D, Pedersen L (1993) Particle mesh Ewald: an N·log(N) method for Ewald sums in large systems. J Chem Phys 98:10089–10092

    Article  CAS  Google Scholar 

  33. Hess B, Bekker H, Berendsen HJC, Fraaije JGEM (1997) LINCS: a linear constraint solver for molecular simulations. J Comput Chem 18:1463–1472

    Article  CAS  Google Scholar 

  34. Parrinello M, Rahman A (1981) Polymorphic transitions in single crystals: a new molecular dynamics method. J Appl Phys 52:7182–7190

    Article  CAS  Google Scholar 

  35. Kumar A, Mahato J, Dixit M, Patwari GN (2019) Progressive hydrophobicity of fluorobenzenes. J Phys Chem B 123:10083–10088

    Article  CAS  Google Scholar 

  36. Lum K, Chandler D, Weeks JD (1999) Hydrophobicity at small and large length scales. J Phys Chem B 103:4570–4577

    Article  CAS  Google Scholar 

  37. Brutschy B (2000) The structure of microsolvated benzene derivatives and the role of aromatic substituents. Chem Rev 100:3891–3920

    Article  CAS  Google Scholar 

  38. Frisch MJ et al. (2016) Gaussian-16 revision B.01 Wallingford CT

Download references

Acknowledgements

Authors gratefully acknowledge SpaceTime-2 supercomputing facility at IIT Bombay for the computing time.

Author information

Authors and Affiliations

  1. Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai, 400076, India

    Anuj Kumar & G. Naresh Patwari

  2. Prithwi Chand Vigyan College, Jai Prakash Vishwavidyalaya, Chapra, Saran, Bihar, 841301, India

    Anuj Kumar

Authors
  1. Anuj Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. Naresh Patwari
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. Naresh Patwari.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kumar, A., Patwari, G.N. Hydration of Fluorobenzenes: A Molecular Dynamics Simulation Investigation. J Indian Inst Sci 100, 221–230 (2020). https://doi.org/10.1007/s41745-019-00157-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s41745-019-00157-1

Search

Navigation