On the Potential Role of the (Pseudo-) Jahn-Teller Effect in the Membrane Transport Processes: Enniatin B and Beauvericin.

The molecular structure of mycotoxins enniatin B and beauvericin, which are used as ionophores, was studied using density functional theory in various symmetry groups and singly charged states. We have shown that the charge addition or removal causes significant structural changes. Unlike the neutral C3 molecules, the stability of the charged C1 structures was explained by the Jahn-Teller or Pseudo-Jahn-Teller effect. This finding agrees with the available experimental X-ray structures of their metal complexes where electron density transfer from the metal can be expected. Hence, the membrane permeability of metal sandwich-structure complexes possessing antimicrobial activities is modulated by the conformational changes.

How Does Pseudo-Jahn-Teller Effect Induce the Photoprotective Potential of Curcumin?

In this paper, the molecular and electronic structure of curcumin is studied. High-symmetric gas-phase tautomers and their deprotonated forms in various symmetry groups are identified. The stability of lower-symmetry structures was explained by using the Pseudo-Jahn-Teller (PJT) effect. This effect leads to stable structures of different symmetries for the neutral enol and keto forms. The presented analysis demonstrated the potential significance of the PJT effect, which may modulate the setting of electronic and vibrational (vibronic) energy levels upon photodynamic processes. The PJT effect may rationalize the photoprotection action and activity of naturally occurring symmetric dyes.

Modeling of the contrast-enhanced perfusion test in liver based on the multi-compartment flow in porous media.

The paper deals with modeling the liver perfusion intended to improve quantitative analysis of the tissue scans provided by the contrast-enhanced computed tomography (CT). For this purpose, we developed a model of dynamic transport of the contrast fluid through the hierarchies of the perfusion trees. Conceptually, computed time-space distributions of the so-called tissue density can be compared with the measured data obtained from CT; such a modeling feedback can be used for model parameter identification. The blood flow is characterized at several scales for which different models are used. Flows in upper hierarchies represented by larger branching vessels are described using simple 1D models based on the Bernoulli equation extended by correction terms to respect the local pressure losses. To describe flows in smaller vessels and in the tissue parenchyma, we propose a 3D continuum model of porous medium defined in terms of hierarchically matched compartments characterized by hydraulic permeabilities. The 1D models corresponding to the portal and hepatic veins are coupled with the 3D model through point sources, or sinks. The contrast fluid saturation is governed by transport equations adapted for the 1D and 3D flow models. The complex perfusion model has been implemented using the finite element and finite volume methods. We report numerical examples computed for anatomically relevant geometries of the liver organ and of the principal vascular trees. The simulated tissue density corresponding to the CT examination output reflects a pathology modeled as a localized permeability deficiency.

B3LYP Study of 3-hydroxynaphthalene-2-carboxanilide para-derivatives.

A systematic DFT investigation of 3-hydroxy-N-phenylnaphthalene-2-carboxamide and its sixteen para-derivatives is presented. The structural analysis showed that the energetically preferred conformation of all derivatives is practically planar and it is stabilised via intramolecular hydrogen bonds occurring between (C)O...H(3)O atomic pairs. The quantum chemically evaluated partition coefficients logarithms correlate well with Quantitative Structure-Activity Relationship models as well as with experimentally determined isocratic retention factors logarithm. Theoretical gas-phase proton affinities of amido and hydroxyl group together with selected partial atomic charges reflect the terminal phenyl substitution effect. These quantities are linearly dependent on the in vitro activity against the Mycobacterium Kansasii. Obtained linear correlation functions based on quantum chemically evaluated microscopic properties and selected experimental data may serve as the effective tool in modern drug design for the description of substitution effect.

Vibronic energy relaxation approach highlighting deactivation pathways in carotenoids.

Energy relaxation between two electronic states of a molecule is mediated by a set of relevant vibrational states. We describe this fundamental process in a fully quantum mechanical framework based on first principles. This approach explains population transfer rates as well as describes the entire transient absorption signal as vibronic transitions between electronic states. By applying this vibronic energy relaxation approach to carotenoids, we show that ß-carotene's transient absorption signal can be understood without invoking the intensely debated S* electronic state. For a carotenoid with longer chain length, we find that vibronic energy relaxation does not suffice to explain all features in the transient absorption spectra, which we relate to an increased ground state structural inhomogeneity. Our modeling approach is generally applicable to photophysical deactivation processes in molecules. As such, it represents a well-founded alternative to data fitting techniques such as global target analysis.

Synthesis and optical properties of various thienyl derivatives of pyrene.

A series of various thienyl derivatives of pyrene were synthesized by Stille cross-coupling procedure. Their structures were characterized by (1)H NMR, (13)C NMR and elemental analysis. The spectroscopic characteristics were investigated by UV-vis absorption and fluorescence spectra. Based on quantum chemical calculations, the energy levels of investigated molecules with respect to the pyrene molecule were also discussed.

Ab initio X(1)0(+) ground state potential curves of Pb···RG dimers (RG = He, Ne, Ar) including spin-orbit effects. Simulation of diffusion coefficients.

CCSD(T) ground state potential curves of Pb···RG systems (RG = He, Ne and Ar) are presented and the importance of the inclusion of spin-orbit effects is discussed. The closed-shell character of the Pb atom at the two-component relativistic level of relativistic theory leads to shallower potential energy curves compared to scalar relativistic open-shell calculations. The pressure-independent cross-diffusion coefficients pD12 have been simulated using the extrapolated two-component CCSD(T) ground state potential curves. The diffusion coefficients from scattering theory are compared with simulations based on molecular dynamics (MD) using the velocity autocorrelation function (VACF) and the Einstein equation. A correction for the proper assessment of the uncertainty in the VACF is proposed. The acceleration of the MD simulation of Pb in RG diffusion is proposed utilizing the RG in Pb diffusion. The dU[TQ]Z/CCSD(T) potential curve of Pb···He (De = 8.667 cm(-1), re = 4.683 Å) supports only one vibrational level. The anharmonicity of this potential is compared to the potential of He···He which also supports only one vibrational level. The comparison is based on the mean square separations of the vibrational wave function.

Combined spectroelectrochemical and theoretical study of electron-rich dendritic 2,5-diaminothiophene derivatives: N,N,N',N'-tetrakis-(4-diphenylamino-phenyl)-thiophene-2,5-diamine.

The in situ spectroelectrochemical and electron spin resonance (ESR) behavior of the recently prepared N,N,N',N'-tetrakis-(4-diphenylamino-phenyl)-thiophene-2,5-diamine 11 is presented. The results are compared to the ones of the parent 2,5-bis-diphenylamino-thiophene 41 as well as to the corresponding high-molar third dendrimer generation 8 containing the same thiophene-2,5-diamine core. The dendritic compound 11 can be reversibly oxidized in three separated steps to yield the corresponding stable monocation 11(•+), dication 11(2+), and tetracation 11(4+). A well resolved ESR spectrum of the corresponding cation radical 11(•+) with dominating splittings from two nitrogen atoms and two hydrogen atoms was observed at the first oxidation peak similar to 41(•+). The shape of the SOMOs orbitals very well correlates with the proposed distribution of the unpaired electron mainly on the thiophene center and neighboring nitrogen atoms. The spin delocalization on the central thiophene moiety in the monocations for all three model compounds 41(•+), 11(•+), and 8(•+) was confirmed. The computed single occupied molecular orbital (SOMO) for trication 11(•3+) is completely different compared to the SOMO of the corresponding monocation 11(•+), and it confirms a largely delocalized unpaired spin density. Dominating diamagnetic product was determined at the third oxidation peak, confirming the formation of a tetracation by a two electron oxidation of ESR silent dication. The positive charge is fully delocalized over the lateral parts of the molecule leading to the high stability of tetracation 11(4+). The estimated theoretical limit energy of the lowest optical transition S0 → S1 is 2.90 eV, and it can be achieved for the 3D dendrimer generation.

Spectroscopic behavior differences between lumazine and alloxazine in the DMSO-water mixture.

The absorption and emission spectra were investigated for lumazine, alloxazine and their cyanated or fluorinated derivatives, respectively. The spectroscopic properties were modulated by varying water concentration in dimethyl sulfoxide (DMSO). Some intriguing experimental results were found for the samples containing 65 % of water and 35% of DMSO. This finding is consistent with previously published molecular dynamics (MD) simulations confirming the concept of the 'local bulk' model. In this case, a notable decrease in absorption and emission intensities was registered, even larger than the water quenching observed in other cases. The changes in midrange DMSO concentrations could be explained by the formation of local solvents structures as predicted by MD, specifically the formation of DMSO·2H2O dimers. Experimentally, the cyano-substituted lumazine has shown a remarkable sensitivity to DMSO concentration. The spectroscopic measurements were interpreted using the density functional theory where the implicit DMSO solvent model was combined with explicit water molecules. Together with its enhanced water solubility, the cyanated lumazine derivate could be used for non-destructive DMSO detection in vitro for applications such as drug uptake monitoring, since DMSO is often used in pharmaceutical practice.

Degradation Mechanisms of 4,7-Dihydroxycoumarin Derivatives in Advanced Oxidation Processes: Experimental and Kinetic DFT Study.

Coumarins represent a broad class of compounds with pronounced pharmacological properties and therapeutic potential. The pursuit of the commercialization of these compounds requires the establishment of controlled and highly efficient degradation processes, such as advanced oxidation processes (AOPs). Application of this methodology necessitates a comprehensive understanding of the degradation mechanisms of these compounds. For this reason, possible reaction routes between HO• and recently synthesized aminophenol 4,7-dihydroxycoumarin derivatives, as model systems, were examined using electron paramagnetic resonance (EPR) spectroscopy and a quantum mechanical approach (a QM-ORSA methodology) based on density functional theory (DFT). The EPR results indicated that all compounds had significantly reduced amounts of HO• radicals present in the reaction system under physiological conditions. The kinetic DFT study showed that all investigated compounds reacted with HO• via HAT/PCET and SPLET mechanisms. The estimated overall rate constants (koverall) correlated with the EPR results satisfactorily. Unlike HO• radicals, the newly formed radicals did not show (or showed negligible) activity towards biomolecule models representing biological targets. Inactivation of the formed radical species through the synergistic action of O2/NOx or the subsequent reaction with HO• was thermodynamically favored. The ecotoxicity assessment of the starting compounds and oxidation products, formed in multistage reactions with O2/NOx and HO•, indicated that the formed products showed lower acute and chronic toxicity effects on aquatic organisms than the starting compounds, which is a prerequisite for the application of AOPs procedures in the degradation of compounds.

Ab initio calculation of structure and transport properties of He X (X = Zn, Cd, Hg) van der Waals complexes.

The ground state ab initio CCSD(T) potential curves using various basis sets (aug-cc-pVXZ-PP (X = D, T, Q, 5)) is obtained for the dimers of helium with IIb group metals. The effect of the position of the (mid) bond-functions on the interaction energy is discussed. A Symmetry Adapted Perturbation Theory decomposition of the interaction energy is provided and the trends in the dimer stabilizing and destabilizing contributions are depicted. The spline fitted potential curves are applied together with rigorous statistical formulae in order to obtain the transport coefficients (viscosity coefficients, diffusion coefficients) and the second virial coefficient both for pure constituents and mixtures. The obtained theoretical results are compared with available experimental data. Molecular dynamics is used to obtain reliable values of the diffusion coefficients for all the systems under study.

On the electrochemistry and spectroelectrochemistry of small model star-shaped compounds: 1,3,5-triaryl-1-methoxybenzenes and 2,4,6-triaryl-1,3,5-trimethoxybenzenes.

Model structures of 1,3,5-triarylbenzenes with a substituted benzene core linked to thienyl or 3,4-ethylenedioxythienyl (EDOT) terminal groups are studied by electrochemical and in situ ESR/UV/Vis/NIR spectroelectrochemical techniques. Oxidative polymerization of the monomers results in C-C coupling of the thiophene moieties in the 5-position, forming dimeric structures with bithiophene linkers as the first step. Both the doubly charged protonated dimer and the new dimer formed after proton release are studied in detail for 2,4,6-tris[2-(3,4-ethylenedioxythienyl)]-1-methoxybenzene. Quite high stability of the doubly charged σ dimer formed on oxidation with unusual redox behavior at the electrode is observed. Density functional calculations of the molecular structure as well as spectroscopic and electronic properties of charged states in 1,3,5-triarylbenzene derivatives in the monomeric, dimeric, and oligomeric form are presented. The complex spectroelectrochemical response of a thin solid film formed on the electrode surface upon potentiodynamic polymerization indicates the existence of different charge states of oligomeric structures within the solid matrix.

Stable radical trianions from reversibly formed sigma-dimers of selenadiazoloquinolones studied by in situ EPR/UV-vis spectroelectrochemistry and quantum chemical calculations.

The redox behavior of the series of 7-substituted 6-oxo-6,9-dihydro[1,2,5]selenadiazolo[3,4-h]quinolines and 8-substituted 9-oxo-6,9-dihydro[1,2,5]selenadiazolo[3,4-f]quinolines with R(7), R(8) = H, COOC(2)H(5), COOCH(3), COOH, COCH(3), and CN has been studied by in situ EPR and EPR/UV-vis spectroelectrochemistry in dimethylsulfoxide. All selenadiazoloquinolones undergo a one-electron reduction process to form the corresponding radical anions. Their stability strongly depends on substitution at the nitrogen atom of the 4-pyridone ring. The primary generated radical anions from N-ethyl-substituted quinolones are stable, whereas for the quinolones with imino hydrogen, the initial radical anions rapidly dimerize to produce unusually stable sigma-dimer (σ-dimer) dianions. These are reversibly oxidized to the initial compounds at potentials considerably less negative than the original reduction process in the back voltammetric scan. The dimer dianion can be further reduced to the stable paramagnetic dimer radical trianion in the region of the second reversible reduction step. The proposed complex reaction mechanism was confirmed by in situ EPR/UV-vis cyclovoltammetric experiments. The site of the dimerization in the σ-dimer and the mapping of the unpaired spin density both for radical anions and σ-dimer radical trianions with unusual unpaired spin distribution have been assigned by means of density functional theory calculations.

Ultrafast photo-induced charge transfer unveiled by two-dimensional electronic spectroscopy.

The interaction of exciton and charge transfer (CT) states plays a central role in photo-induced CT processes in chemistry, biology, and physics. In this work, we use a combination of two-dimensional electronic spectroscopy (2D-ES), pump-probe measurements, and quantum chemistry to investigate the ultrafast CT dynamics in a lutetium bisphthalocyanine dimer in different oxidation states. It is found that in the anionic form, the combination of strong CT-exciton interaction and electronic asymmetry induced by a counter-ion enables CT between the two macrocycles of the complex on a 30 fs timescale. Following optical excitation, a chain of electron and hole transfer steps gives rise to characteristic cross-peak dynamics in the electronic 2D spectra, and we monitor how the excited state charge density ultimately localizes on the macrocycle closest to the counter-ion within 100 fs. A comparison with the dynamics in the radical species further elucidates how CT states modulate the electronic structure and tune fs-reaction dynamics. Our experiments demonstrate the unique capability of 2D-ES in combination with other methods to decipher ultrafast CT dynamics.

Methoxylated flavones with potential therapeutic and photo-protective attributes: Theoretical investigation of substitution effect.

The molecular and electronic structure of parent flavone and 49 (poly)methoxylated flavones (P)MFs were studied theoretically. Selected group of flavonoids consists of compounds naturally occurring in citrus plants or synthetic derivatives of flavone. These compounds exhibit several bioactivities in vitro and in vivo and can protect plants from solar ultraviolet (UV) radiation. Substitution induced structural changes in (P)MFs were correlated with published experimental values of P-glycoprotein inhibition effect. We have demonstrated that the C5-C10 bond length of 1-benzopyran-4-one moiety represents a suitable structural descriptor for this bioactivity. Obtained linear equations for the compounds with substituted and non-substituted C3 position enable the prediction of the potential anti-cancer chemo-preventive effect of the rest of studied (P)MFs. Consequently, potentially more effective substances were suggested. Optical properties of (P)MFs and their relationship with the molecular structure was examined in detail for methanol environment, as well. The multiple linear regression model was applied to assess the correlation between experimental absorption and fluorescence wavelengths with the theoretically predicted ones. The UV photo-protective potential of studied derivatives was estimated from the calculated optical properties.

Relativistic effects in HgHe and HgXe CCSD(T) ground state potential curves. Low-density viscosity simulations of Hg:Xe mixture.

The comparison of coupled cluster with single and double excitations and with perturbative correction of triple excitations [CCSD(T)] ground state potential curves of mercury with rare gases (RG): HgHe and HgXe, at several levels of theory is presented. The scalar relativistic (REL) effects and spin-orbit coupling effects in the ground state potential curves of these weakly bounded dimers are considered. The CCSD(T) ground state potential curves at the level of the Dirac-Coulomb Hamiltonian (DCH) are compared with CCSD(T) curves at the level of 4-component spin-free modified DCH, the scalar 2nd order Douglas-Kroll-Hess (DKH2) and the nonrelativistic (NR-LL) (Lévy-Leblond) Hamiltonian. In addition, London-Drude formula and SCF interaction energy curves are employed in the analysis of different contributions of REL effects in dissociation energies of HgRG and Hg(2) dimers. Moreover, the large anharmonicity of the HgHe ground state potential curve is highlighted. The computationally less demanding scalar DKH2 Hamiltonian is employed to calculate the HgXe, Hg(2) , and Xe(2) all electron CCSD(T) ground state potential curves in highly augmented quadruple zeta basis sets. These potential curves are used to simulate the shear viscosity of mercury, xenon, and mercury-xenon (Hg:Xe) mixture.

Effect of substituents on redox, spectroscopic and structural properties of conjugated diaryltetrazines--a combined experimental and theoretical study.

Two series of new soluble conjugated compounds containing tetrazine central ring have been synthesized. The three-ring compounds have been synthesized by the reaction of aryl cyanide (where aryl = thienyl, alkylthienyl, phenyl or pyridyl) with hydrazine followed by oxidation of the intermediate product with diethyl azodicarboxylate. The five-ring compounds have been prepared using two pathways: (i) reaction of 5-cyano-2,2'-bithiophene (or its alkyl derivative) with hydrazine; (ii) via Suzuki or Stille coupling of 3,6-bis(5-bromo-2-thienyl)-1,2,4,5-tetrazine with a stannyl or boronate derivative of alkylthiophene. UV-vis spectroscopic properties of the synthesized compounds are strongly dependent on the nature of the aryl group, the position of the solubilizing substituent and the length of the molecule, showing the highest bathochromic shift (λ(max) > 440 nm) for five-ring compounds with alkyl groups attached to C(α) carbon in the terminal thienyl ring. An excellent linear correlation has been found for spectroscopically determined and theoretically calculated (TD-B3LYP/6-31G*) excitation energies. With the exception of dipyridyl derivative, the calculated lowest unoccupied molecular orbital (LUMO) level of the investigated molecules changes within a narrow range (from -2.63 to -2.41 eV), in line with the electrochemical data, which show a reversible reduction process with the redox potential varying from -1.23 V to -1.33 V (vs. Fc/Fc(+)). The electrochemically determined positions of the LUMO levels are consistently lower by 0.9 to 1.2 eV with respect to the calculated ones. All molecules readily crystallize. Single crystal studies of 3,6-bis(2,2'-bithien-5-yl)-1,2,4,5-tetrazine show that it crystallizes in a P2(1)/c space group whose structural arrangement is not very favorable to the charge carriers flow within the crystal. Powder diffraction studies of other derivatives have shown that their structural organization is sensitive to the position of the solubilizing substituent. In particular, the presence of alkyl groups attached to C(α) carbon in the terminal thienyl ring promotes the formation of a lamellar-type supramolecular organization.

Anodic oxidation of selenadiazoloquinolones in alkaline media.

Newly synthesized derivatives of 6-oxo-6,9-dihydro[1,2,5]selenadiazolo[3,4-h]quinoline variously substituted at position 7 (R = H, COOH, COCH(3), CN, COOC(2)H(5) and COOCH(3)) are established in strongly alkaline aqueous solutions (0.1 M NaOH; pH ∼ 13) as N(9)-deprotonated structures, but in less alkaline solutions (0.001 M NaOH; pH ∼ 11) the N(9)-protonated oxo tautomeric forms dominate. Upon their anodic oxidation in alkaline solutions, the selenadiazole ring is replaced, forming instead the paramagnetic species analogous to the ortho semiquinone radical anions as monitored by in situ EPR spectroscopy. The quantum chemical calculations for two representative selenadiazoloquinolones (R = H and COOH) and their anodic oxidation products presented are in agreement with experiments.

Charged states of α,ω-dicyano ß,ß'-dibutylquaterthiophene as studied by in situ ESR UV-vis NIR spectroelectrochemistry.

The influence of the molecular structure on the stabilization of charged states was studied in detail by in situ ESR UV-vis NIR spectroelectrochemistry at a novel α,ω-dicyano substituted ß,ß'-dibutylquaterthiophene (DCNDBQT) and the electrochemically generated cation and anion radicals have been proved for the first time. The voltammetry of DCNDBQT results in two separate oxidation steps with the reversible first one. The experimental absorption maxima at 646 and 1052 nm together with the calculated ones (by DFT method) as well as an ESR signal at the first anodic step prove the presence of a radical cation. Three additional optical bands (554, 906, and 1294 nm for CT-transition) can be attributed to the formation of cation radical dimer. The dicationic structure formed in the second oxidation step is not stable. The stabilization proceeds via a dimer formation in two chemical follow-up reactions. The existence of the dimeric structures was proved by ex situ MALDI TOF mass spectrometry. As the substitution by cyano groups opens the route to cathodic reductions, DCNDBQT shows a single quasi-reversible reduction step. Here, the in situ ESR UV-vis NIR spectroelectrochemical measurements and theoretical calculations let us confirm the electrochemical generation of an anion radical. As we found a low number of anion radicals by quantitative ESR spectroelectrochemistry and an appearance of additional bands in the UV-vis NIR absorption spectra, the formation of dimeric structures must be considered and was corroborated by mass spectrometry. The role of dimerization in the reaction mechanism of the DCNDBQT oxidation and reduction are discussed in general. The experimental results were interpreted using the quantum chemical calculations based on density functional theory.

On relativistic effects in ground state potential curves of Zn2, Cd2, and Hg2 dimers. A CCSD(T) study.

The ground state potential curves of the Zn2, Cd2, and Hg2 dimers calculated at different levels of theory are presented and compared with each other as well as with experimental and other theoretical studies. The calculations at the level of Dirac-Coulomb Hamiltonian (DCH), 4-component spin-free Hamiltonian, nonrelativistic Lévy-Leblond Hamiltonian and at the level of simple Coulombic correction to DCH are presented. The potential curves are calculated in an all-electron supermolecular approach including the correction to basis set superposition error (BSSE). Electron correlation is treated at the coupled cluster level including single and double excitations and noniterative triple corrections, CCSD(T). In addition, simulations of the temperature dependence of dynamic viscosities in the low-density limit using the obtained ground state potential curves are presented.