Chalcogen atom effect on the intersystem crossing kinetic constant of oxygen- and sulfur disubstituted heteroporphyrins.

The modulation of the photophysical properties of di-substituted porphyrin rings upon the oxygen and sulfur-for-nitrogen replacement has been investigated at density functional theory (DFT) and its time-dependent formulation (TDDFT). The considered properties range from structural behaviors and excitation energies to spin-orbit coupling (SOC) and nonradiative intersystem kinetic constants. Results show that the SOC strongly increase upon chalcogen substitution and, accordingly, the computed nonradiative kinetic constant also indicate an efficient singlet-triplet intersystem crossing in the sulfur containing macrocycle. The presented results indicate an alternative way to properly modulate the porphyrin's crucial properties for their use in photodynamic therapy, without resorting to the use of heavy atoms.

Theoretical insight into joint photodynamic action of a gold(i) complex and a BODIPY chromophore for singlet oxygen generation.

Density functional theory is herein employed to provide theoretical insight into the mechanism involved in 1O2 photosensitization by a gold-BODIPY combined complex proposed as a promising photodynamic therapy agent. The protocol is thus used to compute the non-radiative rate constants for the S1 → Tj intersystem crossing transitions. Calculations show that while the incorporation of an iodine atom into the core skeleton of BODIPY enhances the singlet-triplet intersystem crossing (ISC) efficiency due to the occurrence of the singlet-triplet transition between states with different orbital characters (ππ* → πn*), the presence of a gold atom, even if not directly anchored to the chromophore core but through a triplet bond, equally entails an increase of the spin-orbit coupling constant due to the heavy atom effect. In this way, the system is able to generate singlet molecular oxygen, the key cytotoxic agent in PDT. Our results fit well with the experimental singlet oxygen quantum yield and cytotoxicity determination.

A DFT study on non-enzymatic degradations of anti-tuberculosis drug isoniazid.

CONTEXT: Isoniazid (INH) is one of the medications most used for tuberculosis (TB) treatment. However, long-term continuous therapy can cause hepatotoxicity and peripheral neuritis. The degradation of INH is an important aspect of the research in the field of drug stability as well as drug formulation for controlling release. It is thought that tautomerization, hydrolysis as well as nucleophilic substitutions can cause decrease in INH as non-enzymatic degradation. Therefore, it is crucial to understand the mechanisms and energies of the major reactions in order to provide reference for future drug formulation and application. This study is an effort to understand the kinetic and thermodynamic properties of the non-enzymatic degradation reactions. The chemical reaction phenomena are investigated using the density functional theory (DFT) method. This study shows that major degradation of INH can be done via tautomerization followed by hydrolysis. The general trends in nucleophilic degradation presented here are consistent with experimental pKa of nucleophiles. METHODS: All DFT calculations were performed using the Gaussian Software Packages (Gaussian 09 revision B.01 and GaussView 5.0.8). MOLEKEL 4.3 software was utilized to visualize the molecular graphics of all relevant species. The optimized molecular geometries were calculated using B3LYP/6-311 + G(d,p) level in the gas phase. The IEF-PCM/B3LYP/6-311 + G(d,p) level was selected for single-point and frequency calculations in aqueous media.

A DFT study on N2O oxidation and methanol synthesis over Bi4O6: single-site catalytic model of α-Bi2Mo3O12.

Catalytic conversion of methane to methanol is one of the most promising processes for effective natural gas resource utilization. In this work, Bi4O6-catalyzed oxidation of methane to methanol with N2O as an oxidizing reactant has been investigated by DFT calculation. For the overall reaction mechanism of three N2O molecules on Bi4O6 catalyst, two catalytic cycles were proposed. Cycle 1 involved the consecutive decomposition of the first two N2O molecules. Cycle 2 corresponded to the decomposition of the third N2O molecule. The activation barriers of the first and second N2O decomposition were computed to be 27.6 and 35.0 kcal/mol, respectively. The third N2O decomposition in cycle 2 required 36.1 kcal/mol activation barriers. Thus, cycle 1 was the main catalytic cycle for N2O as the cycle required lower in barriers than those of the other. Oxidation of methane to methanol on Bi4O7 and Bi4O8 catalysts was supposed to be a two-step mechanism consisting of H3C-H bond breaking and CH3-OH formation. The activation energies of the two steps were 32.7, 41.1, and 21.6, 17.2 kcal/mol for Bi4O7 and Bi4O8, respectively. Thus, methane oxidation over Bi4O8 was found to be more energetically favorable than those of Bi4O7, in which C-H bond breaking is the RDS. The present catalyst could be a promising material for the oxidation of methane to methanol. In summary, the single-site catalytic model study would be beneficial for guiding and searching for potential catalysts in heterogeneously catalyzed N2O decomposition and methanol synthesis as green as possible. However, theoretical investigation of this kind of catalyst's extended model system must be taken into account.

A DFT calculation on nonenzymatic degradation of isoaspartic residue.

ßAsp is an isomer of Asp that can be formed by either deamidation of Asn or isomerization of Asp and known as biological clock. The presence of ßAsp affects the proteolytic stability of the protein. Formation of the isomerized Asp plays a diverse and crucial role in aging, cancer, autoimmune, neurodegenerative, and other diseases. A number of methods have been developed to detect ßAsp, and they are usually used in conjunction. Because of identical mass, differentiation of ßAsp and Asp residues is challenged. Degradation of ßAsp is still unclear and needed to be explored. The energetics and mechanism of five possible pathways for cleavages at ßAsp in peptide model have been investigated by DFT/B3LYP/6-311 + + G(d,p) level of the theory. The calculations show that peptide bond cleavage at α-chain (amino side) due to αOC → αCN ring closure is the most favorable reaction. The result is in agreement with experiment utilizing PSD/CRF method. The second most favorable pathway is due to αOC → ßC ring closure results in ß-chain cleavage. The cleavage products ßAsp and Asp fragments can be used to signify an abundance of ßAsp residue in nonenzymatic condition. Other three cyclizations initiated by either α- or ß-amino nitrogen result in various cleavages, isomerization to Asp, and reconversion to original ßAsp. These three cyclization pathways are obstructed because they require mostly high activation barriers and their intermediates are quite less thermodynamically stable. Thus, computational results also confirm that ßAsp → Asp is prohibited in case of nonenzymatic condition which means that protein L-isoaspartyl O-methyl transferase (PIMT) is needed for this modification.

Conformational analysis of alkali metal complexes of anionic species of aspartic acid, their interconversion and deprotonation: a DFT investigation.

Gas-phase geometry-optimized structures of aspartate complexes of anionic species (Hasp(-)) with lithium, sodium and potassium metal cations and transition-state structures for their interconversions were obtained using the density functional theory computations at the B3LYP/6-311++G(d,p) level of theory. The metal ion affinities of Hasp(-) species and deprotonation energies of [Hasp-M] complexes, M=Li+, Na+ and K+, and their conformers were obtained. Relative energies of the [Hasp-M] complex conformers, reaction energies, thermodynamic properties, rate and equilibrium constants of their complexation are reported. Binding energies of the most stable complexes with Li+, Na+ and K+ are -168.53, -133.34 and -117.68kcal/mol, respectively. The most stable complex conformer as a tri-coordinated form for aspartate complex with Li(+) and bi-coordinated form for aspartate complexes with Na+ and K+ were found.

Coumarins and alkaloids from the roots of Toddalia asiatica.

The EtOAc and MeOH extracts of the roots of Toddalia asiatica Lam. were investigated for the roots' chemical constituents. Two new compounds including 2'R-acetoxytoddanol (1) and 8S-10-O-demethylbocconoline (3) as well as 15 known compounds were isolated. Compound 10 showed strong cytotoxicity against KB cells with an IC50 value of 2.60 µg/mL, which is nearly equal to the ellipticine standard, but showed no activity against Vero cells. Alkaloid 3 displayed weak cytotoxicity against the KB cell line with an IC50 value of 21.69 µg/mL.

Conformational analysis of alkali metal complexes of aspartate dianion and their interactions in gas phase.

The gas-phase geometry optimizations of mono and dinuclear complexes of dianionic species of aspartic acid, asp(2-) with lithium, sodium and potassium cations were carried out using density functional calculation at the B3LYP/6-311++G(d,p) level. The metal ion affinities (MIAs) of asp(2-) species and its complexes [asp-M](-), M=Li(+), Na(+) and K(+) were determined using the vibrational frequency calculations at the same level of theory. The most stable complex conformer for aspartate complexes with Li(+), Na(+) and K(+) alkali cations were found as a tri-coordinated form. All complexations of [asp-M](-) and [asp-M(2)] complexes were found to be exothermic reactions. Relative bond distances between the alkali metal cation M(+) and the binding atoms of aspartate ion in [asp-M](-) and [asp-M(2)] complexes are in decreasing order: K(+)>Na(+)>Li(+).

Tautomeric transformation of temozolomide, their proton affinities and chemical reactivities: A theoretical approach.

The gas-phase geometry optimizations of bare, mono- and dihydrated complexes of temozolomide isomers were carried out using density functional calculation at the M06-2X/6-31+G(d,p) level of the theory. The structures and protonation energies of protonated species of temozolomide are reported. Chemical indices of all isomers and protonated species are also reported. Energies, thermodynamic quantities, rate constants and equilibrium constants of tautomeric and rotameric transformations of all isomers I1↔TZM↔HIa↔HIb↔I2↔I3 in bare and hydrated systems were obtained.

A dye sensitized solar cell using natural counter electrode and natural dye derived from mangosteen peel waste.

Mangosteen peel is an inedible portion of a fruit. We are interested in using these residues as components of a dye sensitized solar cell (DSSC). Carbonized mangosteen peel was used with mangosteen peel dye as a natural counter electrode and a natural photosensitizer, respectively. A distinctive mesoporous honeycomb-like carbon structure with a rough nanoscale surface was found in carbonized mangosteen peels. The efficiency of a dye sensitized solar cell using carbonized mangosteen peel was compared to that of DSSCs with Pt and PEDOT-PSS counter electrodes. The highest solar conversion efficiency (2.63%) was obtained when using carbonized mangosteen peel and an organic disulfide/thiolate (T2/T(-)) electrolyte.

Theoretical study on isomerization and peptide bond cleavage at aspartic residue.

Isomerization and peptide bond cleavage at aspartic residue (Asp) in peptide models have been reported. In this study, the mechanisms and energies concerning the isomerization and peptide bond cleavage at Asp residue were investigated by the density functional theory (DFT) at B3LYP/6-311++G(d,p). The integral equation formalism-polarizable continuum model (IEF-PCM) was utilized to calculate solvation effect by single-point calculation of the gas-phase B3LYP/6-311++G(d,p)-optimized structure. Mechanisms and energies of the dehydration in isomerization reaction of Asp residue were comparatively analyzed with the deamidation reaction of Asn residue. The results show that the succinimide intermediate was formed preferentially through the step-wise reaction via the tetrahedral intermediate. The cleavage at C-terminus is more preferential than those at N-terminus. In comparison to isomerization, peptide bond cleavage is ≈ 20 kcal mol(-1) and lower in activation barrier than the isomerization. So, in this case, the isomerization of Asp is inhibited by the peptide bond cleavage.

A density functional theory study on peptide bond cleavage at aspartic residues: direct vs cyclic intermediate hydrolysis.

In this work, peptide bond cleavages at carboxy- and amino-sides of the aspartic residue in a peptide model via direct (concerted and step-wise) and cyclic intermediate hydrolysis reaction pathways were explored computationally. The energetics, thermodynamic properties, rate constants, and equilibrium constants of all hydrolysis reactions, as well as their energy profiles were computed at the B3LYP/6-311++G(d,p) level of theory. The result indicated that peptide bond cleavage of the Asp residue occurred most preferentially via the cyclic intermediate hydrolysis pathway. In all reaction pathways, cleavage of the peptide bond at the amino-side occurred less preferentially than at the carboxy-side. The overall reaction rate constants of peptide bond cleavage of the Asp residue at the carboxy-side for the assisted system were, in increasing order: concerted < step-wise < cyclic intermediate.

DFT and TDDFT study on the electronic structure and photoelectrochemical properties of dyes derived from cochineal and lac insects as photosensitizer for dye-sensitized solar cells.

Essential parameters related to the photoelectrochemical properties, such as ground state geometries, electronic structures, oxidation potential and electron driving force, of cochineal insect dyes were investigated by DFT and TDDFT at the B3LYP/6-31+G(d,p) level of the theory. The results show that the major charge flow dynamic for all dyes is the HOMO→LUMO transition. The bi-coordinated binding mode, in which the dye uses one carboxyl- and hydroxyl oxygen bound to Ti(IV), is found for all dye-TiO(2) systems. Additionally, the doubly bi-coordinated binding mode in which the dye used both carboxyl groups bound to two Ti(IV) is also possible due to high energy distribution occupied at anchoring groups. This study highlights that most of these insect dyes can be good photosensitizers in dye-sensitized solar cells based on their strong binding to the TiO(2) surface, good computed excited state oxidation potential and thermodynamically favored electron driving force.