DOI: 10.1002/cphc.200700339 Dipole Moment Enhancement in Molecular Crystals from X-ray Diffraction Data Mark A. Spackman,* Parthapratim Munshi, and Birger Dittrich [a] 1. Introduction Molecular properties have long been used to help rationalize intermolecular interactions, and they are key determinants of bulk properties of the liquid or crystal. However, bulk proper- ties cannot be obtained by simple summation of the proper- ties of isolated molecules, and for this reason information about the properties of molecules in crystals can provide val- uable insight into the ways in which these properties are modified by various intermolecular interactions upon incorpo- ration of single molecules into the bulk. One of the simplest such properties, the dipole moment of a molecule in a crystal, is now a common outcome of a quantitative charge density analysis of accurate single crystal X-ray diffraction data, and these experiments are unique in their potential to provide de- tailed information of this kind. In their recent review of chemical information accessible from X-ray charge density analyses, Koritsanszky and Coppens comment that “the evidence overwhelmingly points to an often pronounced, crystal-packing dependent, enhancement of the dipole moments of molecules in crystals.” [1] A striking example of such a pronounced enhancement was reported some time ago for 2-methyl-4-nitroaniline (MNA), where the X- ray-derived dipole moment was determined to be 25(8) D, con- siderably greater than the theoretical value of 8.8 D for an iso- lated molecule, [2] and suggesting an enhancement of  200%. That work has been highly cited as a prime example of the po- tentially very large effect of intermolecular interactions and of the crystal field on the electric properties of molecules in suita- ble crystalline environments. However, a careful and detailed reassessment of this result, based on new X-ray and neutron diffraction data at 100 K, has recently concluded that the mo- lecular dipole moment in the crystal is closer to 12.4(13) D, [3] which represents a considerable enhancement, but far less than previously reported. Since the earlier report of a pro- nounced dipole moment enhancement for MNA has been fol- lowed by a number of similar reports on other molecular crys- tals, the revised result for MNA has led us to question all re- ported examples of enhancements of molecular dipole mo- ments based on multipole refinement of X-ray diffraction data, especially where the enhancement exceeds 100%. We report a critical and comprehensive review of molecular dipole moments derived from X-ray diffraction charge density studies published to date (early 2007). The majority (85%) of these determinations have been published since the first review of this subject by one of us in 1992, [4] and the available data now comprises some 129 determinations based on 70 published studies. Together, these offer the possibility, for the first time, of extracting meaningful trends and identifying outli- ers, with a view to establishing which are physically meaning- ful and which are not. For the latter, we hope to identify more precisely the reasons why they are likely to be in error. For a selection of compounds, we also compare the experimental re- sults with those from partitioning of ab initio periodic Hartree– Fock (PHF) electron densities, as well as results based on the use of Lorentz factor tensors to estimate the electric field aris- ing from surrounding molecules and its effect on the molecu- lar dipole moment. [5] Further insight for all systems could un- doubtedly come from a consideration of the change in direc- tion as well as the change in magnitude of the dipole moment [a] Prof. M.A. Spackman, Dr. P. Munshi, Dr. B. Dittrich School of Biomedical, Biomolecular & Chemical Sciences University of Western Australia Crawley WA 6009 (Australia) Fax:(+ 61)8-6488-1005 E-mail:mas@cyllene.uwa.edu.au Although reliable determination of the molecular dipole moment from experimental charge density analyses on molecular crystals is a challenging undertaking, these values are becoming increas- ingly common experimental results. We collate all known experi- mental determinations and use this database to identify broad trends in the dipole moment enhancements implied by these measurements as well as outliers for which enhancements are pronounced. Compelling evidence emerges that molecular dipole moments from X-ray diffraction data can provide a wealth of in- formation on the change in the molecular charge distribution that results from crystal formation. Most importantly, these ex- periments are unrivalled in their potential to provide this infor- mation in such detail and deserve to be exploited to a much greater extent. The considerable number of experimental determi- nations now available has enabled us to pinpoint those studies that merit further attention, either because they point unequivo- cally to a considerable enhancement in the crystal (of 50% or more), or because the experimental determinations suggest en- hancements of 100% or more—much larger than independent theoretical estimates. In both cases further detailed experimental and theoretical studies are indicated. ChemPhysChem 2007,8,2051–2063 # 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 2051