The Chemistry of Intermolecular Bonding: Organic Crystals, their Structures and Transformations

Abstract

The rationalization, prediction and control of structure and properties of organic condensed phases - crystals, liquids, mesophases, and solutions - is a frontier problem in chemistry, made difficult by the relative weakness and scarce directional selectivity of intermolecular bonding. A survey is given of the present status of theories of molecular recognition and of methods for the computer simulation of intermolecular interactions. The organic crystalline state is first considered: lattice energies; polymorphism and crystal chirality; the possibility of prediction of crystalline structure from molecular structure. Some account is then given of evolutionary modeling schemes, those involving a full dynamic simulation of the transformations of chemical systems: crystal melting; molecular aggregation from solutions into micelles and nuclei. As a perspective for years to come, it appears that molecular dynamics in the classical approximation with empirical potentials will be the method of choice in organic physical and theoretical chemistry.

molecular simulation - molecular recognition - crystal nucleation - crystal structure prediction

References

1 Nicolau KC. Boddy CNC. Braese S. Winssinger N. Angew. Chem. Int. Ed.  1999,  38:  2096 

2 Morrison RT. Boyd RN. Organic Chemistry   9th ed.:  Allyn and Bacon; Boston: 1963.  p.789 

3

Ferretti, V.; Gavezzotti, A.; Gilli, P. Chem. - Eur. J.,
in press.

See for example:

4a Gavezzotti A. Acc. Chem. Res.  1994,  27:  309 

4b Gavezzotti A. Cryst. Rev.  1998,  7:  5 

4c The paper by the ‘Cambridge Collaboration’: Lommerse JPM. Motherwell WDS. Ammon HL. Dunitz JD. Gavezzotti A. Hofmann DWM. Leusen FJJ. Mooij WTM. Price SL. Schweizer B. Schmidt MU. van Eijck BP. Verwer P. Williams DE. Acta Crystallogr  2000,  B56:  697 

5 See for example several papers in Chem. Mater. 1994, 6, Special Issue on the structure and chemistry of the organic solid state, and especially: Dolbecq A. Formiguè M. Batail P. Coulon C. Chem. Mater.  1994,  6:  1413 

6 For a primer on intermolecular interactions see: Rigby M. Smith EB. Wakeham WA. Maitland GC. The Forces Between Molecules   Clarendon Press; Oxford: 1986. 

7

For crystals, where molecules come very close to one another, the dipolar approximation to intermolecular potentials is unsatisfactory because the assumption that intermolecular distances be much larger than dipole dimensions is not valid. For similar reasons, dipole moments for very large molecules (e.g. proteins) are meaningless.

8 For a critical discussion of terms like force, energy, attraction and repulsion in crystals, see: Dunitz JD. Gavezzotti A. Acc. Chem. Res.  1999,  32:  677 

9 Scott WRP. Hunenberger PH. Tironi IG. Mark AE. Billeter SR. Fennen J. Torda AE. Huber T. Kruger P. van Gunsteren WF. J. Phys. Chem.  1999,  103:  3596 

10 MacKerell AD. Wiorkiewicz-Kuczera J. Karplus M. J. Am. Chem. Soc.  1995,  117:  11946 

11 Cornell WD. Cieplak P. Bayly CI. Gould IR. Merz KM. Ferguson DM. Spellmeyer DC. Fox T. Caldwell JW. Kollman PA. J. Am. Chem. Soc.  1995,  117:  5179 

12 Jorgensen WL. Maxwell DS. Tirado-Rives J. J. Am. Chem. Soc.  1996,  118:  11225 

13 See for an overview: Theoretical Aspects and Computer Modeling of the Molecular Solid State   Gavezzotti A. Wiley; Chichester: 1997. 

14 Filippini G. Gavezzotti A. Acta Crystallogr.  1993,  B49:  868 

15 Gavezzotti A. Filippini G. J. Phys. Chem.  1994,  98:  4831 

16 Gilli P. Bertolasi V. Ferretti V. Gilli G. J. Am. Chem. Soc.  2000,  122:  10405 ; and references therein

17

See ref. [13] Thermochemical measurements are needed for comparisons, but thermochemistry does not really appeal to funding agencies. A research proposal entitled ‘Accurate Thermochemical Measurements on Organic Crystals’ admittedly appeals much less than something like ‘Crystal Engineering of Nano-chemical Systems for Supramolecular Devices and Materials’.

18 Gavezzotti A. J. Chem. Soc., Perkin Trans. 2  1995,  1399 ; see also the discussion and references in ref.

19 See for example: Thalladi VR. Nusse M. Boese R. J. Am. Chem. Soc.  2000,  12:  9227 

20a Polymorphism can be a haunting phenomenon because of inadvertent seeding; see the wonderful paper on disappearing polymorphs by: Bernstein J. Dunitz JD. Acc. Chem. Res.  1995,  28:  193 

20b Gavezzotti A. Filippini G. J. Am. Chem. Soc.  1995,  117:  12299 

20c Gavezzotti A. Filippini G. J. Am. Chem. Soc.  1996,  118:  7153 

20d Dunitz JD. Filippini G. Gavezzotti A. Helv. Chim. Acta  2000,  83:  2317 

20e Boese R. Kirchner MT. Dunitz JD. Filippini G. Gavezzotti A. Helv. Chim. Acta  2001,  84:  1561 

21 There is no definite proof that racemic crystals are more dense or more stable than chiral ones, see: Brock CP. Schweizer B. Dunitz JD. J. Am. Chem. Soc.  1991,  113:  9811 ; of course the proof may rest upon some unknown effects so subtle that we cannot account for them at the moment

22 Desiraju GR. Angew. Chem. Int. Ed. Engl.  1995,  34:  2311 

23 Gavezzotti A. J. Am. Chem. Soc.  1991,  113:  4622 

24a Gavezzotti A. Zip-Promet, A Program for the Generation of Crystal Structures from Molecular Structure   University of Milano; Italy: 1999-2000. ; (available for distribution upon request)

24b Gavezzotti A. Minopec, A Program for the Optimization of Lattice Energies   University of Milano; Italy: 1999-2000. ; (available for distribution upon request). ”Zip" stands for ”faster", as the latest version is, although with computers going faster may well mean just making mistakes faster

25 In molecular dynamics, temperature is given its energy equipartition definition, that is T = E(kin)/[R N(dof)], E(kin) being easily obtained from atomic velocities. The internal pressure of a solid or a liquid is easily computed through the virial, a sum of forces that molecules exert against the walls, less the forces due to intermolecular interactions. See: van Gunsteren WF. Berendsen HJC. Angew. Chem. Int. Ed. Engl.  1990,  29:  992 

26 Gavezzotti A. J. Mol. Struct.  1999,  485 

27

A related technique is called Monte Carlo simulation: phase space is sampled by random changes in molecular positions and momenta, rather than by trajectories. MD has a more appealing kinetic flavor, though.

28 Gavezzotti A. Filippini G. Kroon J. van Eijck BP. Klewinghaus P. Chem. - Eur. J.  1997,  3:  893 

29 Gavezzotti A. Chem. - Eur. J.  1999,  5:  567 

30 Gavezzotti A. Chem. - Eur. J.  2000,  6:  2288 

31

See the references to the experimental work in the discussion in ref. [30]

32 These figures could be off by several powers of ten, since the theory of nucleation speed has been said to be the only discipline in chemistry and physics where agreement within nine orders of magnitude is considered a big success see: Oxtoby DW. Acc. Chem. Res.  1998,  31:  91 

33 Keller E. SCHAKAL92, A Program for the Graphic Representation of Molecular and Crystallographic Models   University of Freiburg; Germany: 1993.