Krzysztof Z. Łączkowski

The ORP basis set designed for optical rotation calculations

Details of generation of the optical rotation prediction (ORP) basis set developed for accurate optical rotation (OR) calculations are presented. Specific rotation calculations carried out at the density functional theory (DFT) level for model chiral methane molecule, fluorooxirane, methyloxirane, and dimethylmethylenecyclopropane reveal that the ORP set outperforms larger basis sets, among them the aug‐cc‐pVTZ basis set of Dunning (J. Chem. Phys. 1989, 90, 1007) and the aug‐pc‐2 basis set of Jensen (J. Chem. Phys. 2002, 117, 9234; J. Chem. Theory Comput. 2008, 4, 719). It is shown to be an attractive choice also in the case of larger systems, namely norbornanone, β‐pinene, trans‐pinane, and nopinone. The ORP basis set is further used in OR calculations for 24 other systems, and the results are compared to the aug‐cc‐pVDZ values. Whenever large discrepancies of results are observed, the ORP values are in an excellent agreement with the aug‐cc‐pVTZ results. The ORP basis set enables accurate specific rotation calculations at a reduced cost and thus can be recommended for routine DFT OR calculations, also for large and conformationally flexible molecules.

Synthesis and anticonvulsant activities of novel 2-(cyclopentylmethylene)hydrazinyl-1,3-thiazoles in mouse models of seizures

Abstract Synthesis, characterization and investigation of in vivo anticonvulsant activities of 13 novel cyclopentanecarbaldehyde-based 2,4-disubstituted 1,3-thiazoles are presented. Their structures were determined using 1H and 13C NMR, FAB(+)-MS, HRMS and elemental analyses. The results of anticonvulsant screening reveal that seven intraperitoneally administered compounds: 3a, 3b, 3d, 3e, 3f, 3k and 3m containing F-, Cl-, Br-, CF3-, CH3- and adamantyl substituents demonstrated significant anticonvulsant activity in the pentylenetetrazole model with median effective doses (ED50) ≤ 20 mg/kg, respectively, which was approximately seven-fold lower than that reported for the reference drug, ethosuximide. Noteworthy, none of these compounds impaired animals’ motor skills in the rotarod test.

Synthesis, antimicrobial and anticonvulsant screening of small library of tetrahydro-2H-thiopyran-4-yl based thiazoles and selenazoles

Abstract Synthesis and investigation of antimicrobial activity of 22 novel thiazoles and selenazoles derived from dihydro-2H-thiopyran-4(3H)-one are presented. Additionally, anticonvulsant activity of six derivatives is examinated. Among the derivatives, compounds 4a–f, 4i, 4k, 4 l, 4n, 4o–s and 4v have very strong activity against Candida spp. with MIC = 1.95–15.62 μg/ml. In the case of compounds 4a–f, 4i, 4k, 4 l, 4n, 4o, 4r and 4s, the activity is very strong against some strains of Candida spp. isolated from clinical materials, with MIC = 0.98 to 15.62 μg/ml. Additionally, compounds 4n-v are found to be active against Gram-positive bacteria with MIC = 7.81–62.5 μg/ml. The results of anticonvulsant screening reveal that compounds 4a, 4b, 4m and 4n demonstrate a statistically significant anticonvulsant activity in the pentylenetetrazole model, whereas compounds 4a and 4n showed protection in 6-Hz psychomotor seizure model. Noteworthy, none of these compounds impaired animals’ motor skills in the rotarod test. We also performed quantum chemical calculation of interaction and binding energies in complex of 4a with cyclodextrin.

Accurate calculation of the intensity dependence of the refractive index using polarized basis sets

Using the single and double excitation coupled cluster level of theory (CCSD) and the density functional theory/Becke 3-parameter Lee-Yang and Parr (DFT/B3LYP) methods, we test the performance of the Pol, ZPol, and LPol-n (n = ds, dl, fs, fl) basis sets in the accurate description of the intensity dependence of the refractive index in the Ne atom, and the N(2) and the CO molecules. Additionally, we test the aug-pc-n (n = 1, 2) basis sets of Jensen, and the SVPD, TZVPD, and QZVPD bases by Rappoport and Furche. Tests involve calculations of dynamic polarizabilities and frequency dependent second hyperpolarizabilities. The results are interpreted in terms of the medium constants entering the expressions for optically induced birefringences. In all achiral systems, the performance of the LPol-n sets is very good. Also the aug-pc-2 set yields promising results. Accurate CCSD results available in the literature allow us to select the best basis sets in order to carry out DFT/B3LYP calculations of medium constants in larger molecules. As applications, we show results for (R)-fluoro-oxirane and (R)-methyloxirane.

The B–H–B bridging interaction in B-substituted oxazaborolidine–borane complexes: a theoretical study

Ten oxazaborolidine–borane complexes, nine among them boron-substituted (B–R, R=CH3, CF3, and OCH3), are carefully analysed using quantum-chemistry methods to determine their equilibrium geometries and the corresponding oxazaborolidine–borane interaction energies. It is observed that in all B-trifluoromethyl substituted oxazaborolidine–borane complexes and in one B-methyl substituted complex the B–H–B bond is formed and the interaction energies are 1.5–2.5 times as large as in other investigated complexes. We believe that the presented results may be helpful in experimental recognition of oxazaborolidine–borane complexes which may appear, inter alia, as reaction intermediates.

Synthesis and antimicrobial activities of novel 6-(1,3-thiazol-4-yl)-1,3-benzoxazol-2(3H)-one derivatives

Abstract Synthesis, characterization and investigation of antimicrobial activities of seven new 6-(1,3-thiazol-4-yl)-1,3-benzoxazol-2(3H)-ones are presented. Their structures were determined using 1H NMR, 13C NMR and elemental analyses. The compounds possess some biological activity against Gram-positive bacteria, especially against Micrococcus luteus belonging to opportunistic pathogens, with an MIC of 31.25 μg/mL.

Synthesis, biological evaluation and molecular docking studies of novel quinuclidinone derivatives as potential antimicrobial and anticonvulsant agents

Synthesis and investigation of antimicrobial and anticonvulsant activity of eleven novel quinuclidinone-thiazole derivatives are presented. Among the derivatives, compounds 3a–3f showed a broad-spectrum antibiotic activity against all reference Gram-positive or Gram-negative bacteria and fungi. These compounds exhibited very strong or good bactericidal activity towards Gram-positive bacteria (Staphylococcus spp., Micrococcus spp. and Bacillus spp.) with MIC = 0.48–15.62 µg/ml. The tested substances 3a–e and 3f were found also to be active against reference Gram-negative bacteria (Bordetella spp. and rod-shaped bacteria of the family Enterobacteriaceae) with MIC = 31.25–500 µg/ml. The fungicidal effect of compounds 3a–e was very strong or strong against Candida spp. with MIC = 1.95–31.25 µg/ml. The results of anticonvulsant screening revealed that the compound 3f demonstrated high anticonvulsant activity in electrically-induced seizure models, i.e., MES and 6-Hz tests. It was also effective in pilocarpine-induced model of seizures. Noteworthy, 3f did not impair animals’ motor skills in the rotarod test. Molecular docking studies of all compounds into the active sites of microbial enzymes indicated secreted aspartic proteinase as possible antifungal target and DNA gyrase subunit A as possible antibacterial target.

Theoretical evaluation of NMR shifts in polycyclic aromatic hydrocarbons

ABSTRACT Using computational chemistry methodology, we evaluate the proton magnetic shieldings and the corresponding chemical shifts of 12 polycyclic aromatic hydrocarbons that derive from chrysene, perylene and picene. Due to the large size of the studied compounds, we resort to density functional theory (DFT) and use it together with the B3LYP and the KT1 functionals. After a systematic method and basis set selection study carried out on methane, benzene and anthracene, the DFT(B3LYP) method and the 6-31G*, 6-31G** and 6-311++G** bases are selected to carry out the calculations, because of the efficiency in providing shifts close to the experimental data available. Additionally, we select the DFT(KT1) method together with the aug-pcS-1 basis set, and HF/6-31G* shifts are also calculated. In order to estimate the error in the theoretical results, we take as reference accurate experimental chemical shifts obtained for the molecules under investigation. Extra measurements are needed for this purpose and are included in the present work. The best combination of method and basis set is DFT(B3LYP)/6-31G**, proving to be very efficient in getting shifts close to experiment at a relatively low computational cost, and therefore we recommend it for the evaluation of proton shifts in larger polycyclic aromatic hydrocarbons.

Synthesis and biological evaluation of novel 2-(1H-imidazol-2-ylmethylidene)hydrazinyl- 1,3-thiazoles as potential antimicrobial agents

Abstract Synthesis, characterization, and investigation of antimicrobial activities of nine novel imidazolylthiazoles are presented. Their structures were determined using 1H NMR, 13C NMR, and elemental analysis. Compounds 3e and 3i show very strong or strong bacteriostatic or bactericidal activity [minimal bactericidal concentration/minimal inhibitory concentration (MIC)=2–64] against Staphylococcus spp. (MIC=7.81–15.62 μg/mL), Micrococcus luteus ATCC 10240 (MIC=1.95–3.91 μg/mL), and Bacillus spp. (MIC=3.91–15.62 μg/mL). Compounds 3e and 3i also show the highest fungicidal effect (minimal fungicidal concentration/MIC=2–4) against reference strains of fungi belonging to Candida spp. with MIC ranging from 3.91 to 31.25 μg/mL.

Theoretical calculation of NMR shifts in newly developed antibacterial 4-formylbenzoic acid-based thiazoles

We evaluated the proton chemical shieldings and the corresponding chemical shifts of ten newly developed antibacterial 4-formylbenzoic acid-based thiazoles, using computational chemistry methodology. Due to the large size of the studied molecules, we resorted to density functional theory. After a systematic method and basis set selection study carried out on methane, benzene, and thiazole, we selected the M06 DFT functional together with the aug-pcS-1 basis set to carry out the calculations on the larger systems. This combination of functional and basis set seems to be very efficient in providing shifts close to the experimental data available at a relatively low computational cost. The theoretical results for the molecules under investigation were compared to the experimental chemical shifts available, and reasonable agreement was reached in all cases, allowing the theoretical calculations a more detailed analysis of the one-dimensional experimental spectra, i.e. the assignment of individual experimental aromatic signals to specific protons of the phenyl rings, that was not possible based solely on the experimental results. Considering this, we can recommend the M06 functional and the aug-pcS-1 basis set for the evaluation of proton shifts in larger 4-formylbenzoic acid-based thiazoles.