An algorithm, Stigmata, is described, which extracts structural commonalities from chemical datasets. It is discussed using several illustrative examples and a pharmaceutically interesting set of dopamine D2 agonists. The commonalities are determined using two-dimensional topological chemical descriptions and are incorporated into the key feature of the algorithm, the modal fingerprint. Flexibility is built into the algorithm by means of a user-defined threshold value, which affects the information content of the modal fingerprint. The use of the modal fingerprint as a diversity assessment tool, as a database similarity query, and as a basis for color mapping the determined commonalities back onto the chemical structures is demonstrated.

The photon echo experiment probes the dynamical processes that cause the decay of a coherent macroscopic electric polarization. Application of the technique to liquid solutions permits the study of the molecular motions that are strongly coupled to an electronic transition. We develop a semiclassical approximation to the photon echo observable, based on the use of Wigner equivalents of quantum operators, that we demonstrate to be accurate for all values of the delay time between the two pulses of the photon echo. In this approximation, the echo arises from fluctuations in the spectroscopic transition frequency, as the fluid evolves on a potential surface that is the arithmetic mean of the ground and excited state surfaces. The echo may then be calculated from nonequilibrium molecular dynamics simulations. We use this method to calculate the photon echo for a fluid of dipolar soft spheres. The results are compared to calculations of the absorption spectrum for this model, and to previous calculations of the effects of solvent dynamics on optical spectroscopic observables.

The contribution that the Chemical Abstracts structural database (CAST-3D) and the Maybridge database (MAY) would make to diversifying the structural information and property space spanned by our corporate database (CBI) is assessed. A subset of the CAST-3D database has been selected to augment the structural diversity of various electronic databases used in computer-assisted drug design projects. The analysis of the MAY database directly offers the potential to expand the CBI compound library, but also provides a source for structural diversity in a format suitable for computer-assisted database searching and molecular design. The analysis performed is twofold. First, a nonhierarchical clustering technique available in the Daylight clustering package is applied to evaluate the structural differences between databases. The comparison is then extended to analyze various structure-derived property spaces calculated from molecular descriptors such as the logarithm of the octanol-water partition coefficient (CLOGP), the molar refractivity (CMR) and the electronic dipole moment (CDM). The diversity contribution of each database to these property spaces is quantified in relation to our corporate database.

We present calculations of the inhomogeneously broadened absorption line shape associated with a single vibronic transition in a polar chromophore at infinite dilution in a polar solvent. The permanent electric dipole moment of the solute is assumed to change upon electronic excitation. The line shape is related to the dipolar solvation free energy of a fictitious solute with a complex-valued dipole moment. This relation allows methods of equilibrium fluid theory to be applied to the line shape calculation. In order to assess the accuracy of theoretical predictions, we determine line shapes from Monte Carlo simulations for a dipolar hard sphere solute in a dipolar hard sphere solvent. Simulated line shapes are compared to predictions of the mean spherical approximation (MSA) and to a simplified nonlinear solvation theory. The MSA is found to show semiquantitative agreement with simulation results, despite the large value of the solute’s ground-state dipole moment and of its dipole moment change upon excitation. Simulation results are also compared to the relation between the first and second moments of the spectrum that is predicted by any linearized solvation theory. The comparison suggests that an ‘‘exact’’ linearized theory would provide accurate predictions for absorption spectra in polar solutions.

We treat the statically broadened absorption spectrum of a polar chromophore, whose dipole moment is assumed to change upon electronic excitation, at infinite dilution in a polar solvent. Calculations based on the reference hypernetted chain (RHNC) equation are compared to results from the mean spherical approximation (MSA) and to Monte Carlo simulations. The RHNC calculations are in quantitative agreement with simulation results for a strongly coupled solute–solvent system.