Tadeusz Pluta

In this work, the synthesis, structural analysis and anticancer properties of 5-methyl-9-trifluoromethyl-12H-quino[3,4-b][1,4]benzothiazinium chloride (3) are described. Compound 3 was synthesized by reacting 1-methyl-4-butylthio-3-(benzoylthio)quinolinium chloride with 4-(trifluoromethyl)aniline, respectively. The structure of the resulting product was determined using ¹H-NMR and ¹³C-NMR spectroscopy as well as HR-MS spectrometry. The spatial geometry of agent 3 and the arrangement of molecules in the crystal (unit cell) were also confirmed using X-ray diffraction. The tetracyclic quinobenzothiazinium system is fairly planar because the dihedral angle between the planes formed by the benzene ring and the quinoline system is 173.47°. In order to obtain insight into the electronic charge distribution of the investigated molecule, electronic structure calculations employing the Density Functional Theory (DFT) were performed. Moreover, antiproliferative activity against a set of pancreatic cancer cell lines was tested, with compound 3 showing IC₅₀ values against human primary pancreatic adenocarcinoma BxPC-3 and human epithelioid pancreatic carcinoma Panc-1 of 0.051 µM and 0.066 µM, respectively. The IC₅₀ value of cytotoxicity/cell viability of the investigated compound assessed on normal human lung fibroblasts WI38 was 0.36 µM.

In this article, we introduce a simple but reliable method to calculate the electric field dependence of the isotropic hyperfine coupling tensor A_iso for free radicals. This dependence, also referred to as the Bloembergen effect, can be of interest in analyzing EPR experiments for solid-state materials but is rarely studied for isolated radicals in the gaseous phase. The proposed method uses the numerical differentiation of the field-perturbed A tensor and, consequently, as a purely numerical method, does not depend on a quantum chemical method used to determine the hyperfine tensor A. To test the performance of the proposed method, we used a set of 28 systems, including seven organic radicals, the majority of which were taken from a recent benchmark study by Bartlett's group. We employed the well-tested and robust density functional theory (DFT) functional, namely CAM-B3LYP, and the variant of the CCSD method based on local pair natural orbitals, namely DLPNO-CCSD to calculate the A_iso tensor itself, and all first derivatives or Bloembergen effect constants a_i⁽¹⁾.

Static electric properties, from the dipole moment to the second-hyperpolarizability tensor γ, of the three-membered, isoelectronic ring molecules: fluorene (FL), carbazole (CR), and dibenzofuran (DBF) have been calculated at various levels of approximation. The electron correlation effects have been included at the Coupled Cluster (CC) level, using CCSD and CC2 versions of the method. DFT calculations with the CAM-B3LYP functional have been also performed and the results compared to the CC values. Electric property-tailored Pol basis set and its more compact Z3Pol version have been employed in all static calculations. Differences between dipole polarizability values computed at the Pol and Z3Pol bases have been found to be almost negligible. Therefore, all components of the frequency-dependent dipole polarizability tensor α(-ω;ω) have been determined at the CAM-B3LYP/Z3Pol level. Divergence occurring at electronic resonances have been eliminated by using the Complex Polarization Propagator (CPP) formalism explicitly introducing an imaginary iΓ parameter to account approximately for the finite life-time of the excited state. The imaginary part of the dipole polarizability Im α(-ω;ω) has been calculated for a wide range of external radiation energies up to 10 eV, and its maxima have been compared to the calculated vertical electronic excitation energies.

The performance of more than 40 density functionals in predicting indirect spin–spin coupling constants (SSCCs) in the Kohn–Sham basis set limit was tested. For comparison, similar calculations were performed using the RHF, SOPPA, SOPPA(CC2), and SOPPA(CCSD) methods, and the results were estimated toward the complete basis set (CBS) limit. The SSCCs of nine small molecules (N₂, CO, CO₂, NH₃, CH₄, C₂H₂, C₂H₄, C₂H₆, and C₆H₆) were calculated using the dedicated Jensen pcJ-n polarization-consistent basis sets and used for the CBS limit estimations within the Kohn–Sham limit. These CBS results were compared with calculations using the aug-cc-pVTZ-J basis set. Among the 41 studied DFT methods, the tHCTHhyb, HSEh1PBE, HSE2PBE, wB97XD, wB97, and wB97X functionals reproduced accurately the experimental ¹J(XH) SSCCs and ³J(HH60) and ²J(HH_gem) in ethane. Similarly, the functionals HSEh1PBE, HSE2PBE, wB97XD, wB97, and wB97X predicted accurately ¹J(CC), and B98, B97-1, B97-2, PBE1PBE, B1LYP, and O3LYP provided accurate ¹J(CO) results in the CO molecule. A very good performance for the calculation of the SSCCs based on the use of the relatively small basis set aug-cc-pVTZ-J was observed.

It is shown that a linear correlation exists between nuclear shielding constants for nine small inorganic and organic molecules (N₂, CO, CO₂, NH₃, CH₄, C₂H₂, C₂H₄, C₂H₆ and C₆H₆) calculated with 47 methods (42 DFT methods, RHF, MP2, SOPPA, SOPPA(CCSD), CCSD(T)) and the aug‐cc‐pVTZ‐J basis set and corresponding complete basis set results, estimated from calculations with the family of polarization‐consistent pcS‐n basis sets. This implies that the remaining basis set error of the aug‐cc‐pVTZ‐J basis set is very similar in DFT and CCSD(T) calculations. As the aug‐cc‐pVTZ‐J basis set is significantly smaller, CCSD(T)/aug‐cc‐pVTZ‐J calculations allow in combination with affordable DFT/pcS‐n complete basis set calculations the prediction of nuclear shieldings at the CCSD(T) level of nearly similar accuracy as those, obtained by fitting results obtained from computationally demanding pcS‐n calculations at the CCSD(T) limit. A significant saving of computational efforts can thus be achieved by scaling inexpensive CCSD(T)/aug‐cc‐pVTZ‐J calculations of nuclear isotropic shieldings with affordable DFT complete basis set limit corrections. Copyright © 2011 John Wiley & Sons, Ltd.