Henryk Koroniak

Toward a Physical Interpretation of Substituent Effects: The Case of Fluorine and Trifluoromethyl Groups

The application of ab initio and DFT computational methods at six different levels of theory (MP2/cc-pVDZ, MP2/aug-cc-pVTZ, B3LYP/cc-pVDZ, B3LYP/aug-cc-pVTZ, M06/cc-pVDZ, and M06/aug-cc-pVTZ) to meta- and para-substituted fluoro- and trifluoromethylbenzene derivatives and to 1-fluoro- and 1-trifluoromethyl-2-substituted trans-ethenes allowed the study of changes in the electronic and geometric properties of F- and CF3-substituted systems under the impact of other substituents (BeH, BF2, BH2, Br, CFO, CHO, Cl, CN, F, Li, NH2, NMe2, NO, NO2, OH, H, CF3, and CH3). Various parameters of these systems have been investigated, including homodesmotic reactions in terms of the substituent effect stabilization energy (SESE), the π and σ electron donor-acceptor indexes (pEDA and sEDA, respectively), the charge on the substituent active region (cSAR, known earlier as qSAR), and bond lengths, which have been regressed against Hammett constants, resulting mostly in an accurate correspondence except in the case of p-fluorobenzene derivatives. Moreover, changes in the characteristics of the ability of the substituent to attract or donate electrons under the impact of the kind of moiety to which the substituent is attached have been considered as the indirect substituent effect and investigated by means of the cSAR model. Regressions of cSAR(X) versus cSAR(Y) for any systems X and Y allow final results to be obtained on the same scale of magnitude.

Peptide p-nitrophenylanilides containing (E)-dehydrophenylalanine—synthesis, structural studies and evaluation of their activity towards cathepsin C

Tetrapeptide p-nitroanilides containing (E)-dehydrophenylalanine were synthesized and evaluated as inhibitors and substrates of cathepsin C. Peptides containing a free, unblocked amino group appeared to be quite good substrates of the enzyme, whereas fully protected peptides acted as very weak inhibitors. Structural studies by means of NMR and CD, alongside with molecular modelling, have proved that these peptides are hydrolysed in one step by direct removal of p-nitroaniline from the tetrapeptide.

Synthesis of some 5-perfluoroalkenyl derivatives of uracil

Abstract 1,3-Dimethyl-5-iodouracil reacts smoothly with perfluorovinyl- (and E/Z-pentafluoropropenyl)-zinc iodides in the presence of Pd° as a catalyst yielding the appropriate 5-perfluoroalkenyl derivatives of uracil at high and moderate yield. In an analogous reaction, 1,3-dimethyl-6-iodouracils did not yield the expected coupling products.

FACILE LARGE SCALE SYNTHESIS OF 5-ALKYLURACILS

(1993). FACILE LARGE SCALE SYNTHESIS OF 5-ALKYLURACILS. Organic Preparations and Procedures International: Vol. 25, No. 5, pp. 563-568.

The further investigation of physical and photochemical properties of quasimetacyclophane derived from thymine.

The thymine derived quasimetacyclophane exist in two conformers a and b. The absorption spectra of a and b were evaluated and the conformational equilibrium in different solvents /H2O : EtOH/ were examined. The rate constant k−1 for reaction b→a was established as well as Ea.

Fluorinated enamines of nucleobases as precursors of nucleoside analogues. Synthesis, spectroscopic and structural studies

The 1H and 19F NMR spectra of N-α-fluoro-β-trifluoromethylenamines and isostructural N-β-fluoro-β-trifluoromethylenamines of nucleobases dissolved in CDCl3 and DMSO-d6 have shown distinct differences associated with the conformational conversion between the Z and E stereoisomers. In the E stereoisomer the tetrafluoropropenyl group is rotated relative to the heteroring plane, whereas the Z stereoisomer assumes the most planar structure. The flat conformation of the Z stereoisomer is stabilised by internal hydrogen bonding between Cα–H and the carbonyl oxygen (pyrimidinic bases) or the endocyclic nitrogen (purinic bases). Large variations in the magnitudes of the chemical shifts of Cβ–H, Cα–F, C6–H and C8–H were observed, i.e. the chemical shift increased with increasing polarity and ability of DMSO-d6 to establish intermolecular hydrogen bonds in competition with intramolecular hydrogen bonds. The (Z)-N4-benzoyl-N1-(1,3,3,3-tetrafluoroprop-1-enyl)cytosine crystals undergo a phase transition at 230 K induced by the tetrafluoropropenyl substituent reorientations. Between 300 and 230 K the molecules are present in two conformations, and below 230 K the molecules gradually assume five conformations, remaining in a stable equilibrium with intermolecular forces, evidenced by single-crystal X-ray diffraction.

Cyclization reactivities of fluorinated hex-5-enyl radicals

A kinetic study of the effect of fluorine substitution on the rates and regiochemistry of hex-5-enyl radical cyclization is reported. One or more fluorines on or proximate to the double bond of the radical have relatively little electronic effect on either rate or regiochemistry, whereas fluorines substituted at the radical end can have a dramatic impact on both. The relative reactivities of such partially-fluorinated hex-5-enyl radicals can be understood largely in terms of polar effects on the transition state, but radical pyramidalization and, to a lesser extent, addition thermodynamics play a role. The relationship between these fluorine substituent effects and the cyclopolymerizations of fluorinated α,ω-dienes are discussed.

Structural studies of some 5-(perfluoroalkenyl) uracils

Abstract Structures of the most stable conformers of derivatives of 5-vinyluracil and fluorinated analogues have been determined using MM and semiempirical MNDO calculations. It has been found that the most stable conformers of 5-trifluorovinyl and 5- E / Z -pentafluoropropenyl groups are almost perpendicular to the plane of the uracil ring. These findings are in good agreement with X-ray data obtained for 1,3,6-trimethyl-5-trifluorovinyluracil. The calculated energy barrier for rotation of exocylic 5-substituents depends on the structure of the fluorinated fragments as well as on the nature of the substituent at the 6-position of uracil. A methyl group at the 6-position causes steric hindrance and significantly disturbs the rotation of fluorinated groups.

The Synthesis of 5-Bromo-1,3-Dimethyluracil and its 6-Alkyl Derivatives

Abstract Bromination of 1,3-dimethyluracil and 6-alkyl-1,3-dimethyluracils with N-bromosuccinimide leads to the corresponding 5-bromo substituted uracils in high yields.

The effect of fluorine substituents on the structure of cyclopropane. The structure of 4,4,8,8-tetraf1uorotricyclo-(5.1.0.0.3,5) octane

Abstract The first x-ray structure determination of a fluorine-substituted cyclopropane is reported. The title compound was synthesized via bis difluorocarbene addition to 1,4-cyc1ohexadiene and its structure determined via x-ray crystallographic techniques. Its cyclopropane bondlengths (1.552 and 1.452) are very similar to those reported earlier in a microwave study of the parent 1,1-difluorocyclopropane, while its cyclohexane ring is virtually planar.