Christoph Rücker

QSPR Using MOLGEN-QSPR: The Example of Haloalkane Boiling Points

MOLGEN-QSPR is a software newly developed for use in quantitative structure property relationships (QSPR) work. It allows to import, to manually edit, or to generate chemical structures, to detect duplicate structures, to import or to manually input property values, to calculate the values of a broad pool of molecular descriptors, to establish QSPR equations (models), and using such models to predict unknown property values. In connection with the molecule generator MOLGEN, MOLGEN-QSPR is able to predict property values for all compounds in a predetermined structure space (inverse QSPR). Some of the features of MOLGEN-QSPR are demonstrated on the example of haloalkane boiling points. The data basis used here is broader than in previous studies, and the models established are both more precise and simpler than those previously reported.

Multiply metallated organic intermediates: a tris(lithiomethyl)cyclohexane and a hexalithiotrimethylcyclohexanetriolate

Lithium di-t-butylbiphenyl (LiDBB) readily cleaves alkyl-sulphur bonds to yield long-lived organolithiums. Using this reagent trilithio species (2b) was obtained from tris-phenylthioether (1b). The organometallic intermediates (2b) and (5b) were characterised by their reactions with electrophiles (e.g. D2O, CO2, Me3Si-OTf, Me-OTf) to yield di- and hexasubstituted cyclohexanes (3) and (6). Prolonged treatment of the trilithoxy tris-phenylthioether (1c) with excess LiDBB followed by addition of D2O and aqueous work-up gave a methyl-deuterated trimethylcyclohexanetriol (D2.5-3aα) demonstrating that at least one penta- and one hexalithio intermediate are involved. The structure of the latter intermediate could not be established unambiguously, but the unsymmetrical 1,1-dilithiated species (22) is prefered over the symmetrical hexalithio species (2c) on the basis of extensive transmetallation observed at the tetra- or pentalithio stage ( as seen in the deuterated phenylthiomethylcyclohexanetriol (15) and the absence of compelling evidence for the symmetrical tri(deuteriomethyl)cyclohexanetriol (3aβ), as judged from the CH3, CH2D, and CHD2 ratios in the deuterated product (D2.5-3aα).

Understanding the properties of isospectral points and pairs in graphs : the concept of orthogonal relation

The mathematical property “orthogonal relationship” is used in proving the fact that isospectrality, isocodality and isocoefficiency of vertices within a graph are all equivalent. The same is true for isospectrality, “strict isocodality” and “strict isocoefficiency” of pairs (including edges) within a graph, whereas the “weak” versions of the latter properties are necessary but not sufficient for isospectrality of pairs. Similarly, necessary and sufficient conditions for isospectrality of vertices and pairs in different graphs are derived. In all these proofs, the concept of “orthogonal relation” plays a major role in that it allows the use of tools of elementary linear algebra.

Exploring the limits of graph invariant- and spectrum-based discrimination of (sub)structures

The limits of a recently proposed computer method for finding all distinct substructures of a chemical structure are systematically explored within comprehensive graph samples which serve as supersets of the graphs corresponding to saturated hydrocarbons, both acyclic (up to n = 20) and (poly)cyclic (up to n = 10). Several pairs of smallest graphs and compounds are identified that cannot be distinguished using selected combinations of invariants such as combinations of Balabans index J and graph matrix eigenvalues. As the most important result, it can now be stated that the computer program NIMSG, using J and distance eigenvalues, is safe within the domain of mono- through tetracyclic saturated hydrocarbon substructures up to n = 10 (oligocyclic decanes) and of all acyclic alkane substructures up to n = 19 (nonadecanes), i.e., it will not miss any of these substructures. For the regions surrounding this safe domain, upper limits are found for the numbers of substructures that may be lost in the worst case, and these are low. This taken together means that the computer program can be reasonably employed in chemistry whenever one is interested in finding the saturated hydrocarbon substructures. As to unsaturated and heteroatom containing substructures, there are reasons to conjecture that the methods resolving power for them is similar.

Advances in Mathematical Chemistry and Applications Volume 1 (Revised Edition)

Volume 1 includes chapters on mathematical structural descriptors of molecules and biomolecules, applications of partially ordered sets (posets) in chemistry, optimal characterization of molecular complexity using graph theory, different connectivity matrices and their polynomials, use of 2D fingerprints in similaritybased virtual screening, mathematical approaches to molecular structure generation, comparability graphs, applications of molecular topology in drug design, density functional theory of chemical reactivity, application of mathematical descriptors in the quantification of drug-likeness, utility of pharmacophores in drug design, and much more.