An algorithm is introduced that enables a fast generation of all possible prototropic tautomers resulting from the mobile H atoms and associated heteroatoms as defined in the InChI code. The InChI-derived set of possible tautomers comprises (1,3)-shifts for open-chain molecules and (1,n)-shifts (with n being an odd number >3) for ring systems. In addition, our algorithm includes also, as extension to the InChI scope, those larger (1,n)-shifts that can be constructed from joining separate but conjugated InChI sequences of tautomer-active heteroatoms. The developed algorithm is described in detail, with all major steps illustrated through explicit examples. Application to approximately 72,500 organic compounds taken from EINECS (European Inventory of Existing Commercial Chemical Substances) shows that around 11% of the substances occur in different heteroatom-prototropic tautomeric forms. Additional QSAR (quantitative structure-activity relationship) predictions of their soil sorption coefficient and water solubility reveal variations across tautomers up to more than two and 4 orders of magnitude, respectively. For a small subset of nine compounds, analysis of quantum chemically predicted tautomer energies supports the view that among all tautomers of a given compound, those restricted to H atom exchanges between heteroatoms usually include the thermodynamically most stable structures.

For molecules with mobile H atoms, the result of quantitative structure-activity relationships (QSAR) depends on the actual position of the respective hydrogen atoms. Thus, to obtain reliable results, tautomerism needs to be taken into account. A new algorithm to create all tautomer forms of a given molecule based on the mobile H-layer information in the InChI (The IUPAC International Chemical Identifier) code is presented. Unlike published tautomer generation models, this requires no particular rule set. The algorithm eliminates atoms not participating in tautomerism and finally generates all possible combinations. The algorithm was applied to ca. 70,000 structures of the EINECS (European Inventory of Existing Commercial Chemical Substances) database. Ca. 7,500 structures with mobile H atoms were detected. In total, around 200,000 tautomers were generated. Typically, the number of tautomers for single compounds is below 25, but for some molecules this number is extremely large.Two estimation models, one for the soil sorption coefficient and one for the water solubility, were applied to the subset of compounds with tautomerism. For each substance, the variability of the results due to the different tautomer forms has been inspected. Calculation results exceeding the range of reasonable values have been excluded from the study. The average variation of the soil sorption coefficient within tautomers of individual compounds was almost 0.5 in logarithmic units, and differences up to 3 orders of magnitude were obtained for particular chemicals. For the water solubility, the average variation was between 1 and 2 orders of magnitude, with maximum differences of more then ten logarithmic units.

Significance: Tetrabrominated naphthalene dianhydride was efficiently functionalized with four thiophene rings to yield compound 1, which is soluble in organic solvents unlike its precursors. Following imidation, the four thiophene arms were synthetically extended by iterating bromination and Stille-coupling steps to yield compound 3 in 32% yield. Both compounds 2 and 3 displayed long-wavelength absorption maxima (514 nm and 664 nm, respectively) due to the donor-acceptor interaction between the thiophene (donor) and naphthalene diimide (acceptor) moieties. Field-effect-transistor (FET) devices containing either 2 or 3 showed satisfactory performance under both pchannel and n-channel operation.Comment: Naphthalene diimides are highly electron-deficient molecules and therefore act as excellent electron acceptors. Compounds 1 and 2 are interesting because, although the four thiophene moieties are non-coplanar with the naphthalene core, a significant red shift (ca. 200 nm) in the absorption maximum is observed relative to the unfunctionalized dianhydride. Moreover, although compound 2 seems perfectly suited for electrochemical polymerization, its irreversible electrochemistry under oxidative conditions precludes the possibility of clean electropolymerization.