Synthesis, Anticancer, Antioxidant, Anti-Inflammatory, Antimicrobial Activities, Molecular Docking, and DFT Studies of Sultams Derived from Saccharin.

A series of N-substituted saccharins namely 2-(1,1-dioxido-3-oxobenzo[d]isothiazol-2(3H)-yl) acetonitrile (2) and (alkyl 1,1-dioxido-3-oxobenzo[d]isothiazol-2(3H)-yl) acetate (3a-g) were synthesized, in moderate to excellent yields, from commercially available starting materials by two different approaches and their chemical structures were characterized by spectroscopic techniques (1H-NMR, 13C-NMR, IR, and MS). All the synthesized compounds were evaluated for their anti-inflammatory toward IL-6 and TNF-α, antioxidant, as well as their anticancer activities against hepatic cancer cells. In addition, their anti-fungal and antibacterial activities against both Gram-positive and Gram-negative bacteria were tested. All the tested compounds have exhibited excellent (3a, d, e) to moderate anti-inflammatory activity. Additionally, esters (3b, f) and nitrile (2) showed excellent antioxidant activity. Furthermore, ester 3f, with isopropyl ester, exhibited the highest cytotoxic activity compared to the other esters. Moreover, all compounds were evaluated as selective inhibitors of the human COX-1 enzyme using molecular docking by calculating the free energy of binding, inhibition constant, and other parameters to find out the binding affinity. The molecular study showed that esters (3d, f) and nitrile (2) revealed the highest binding affinities, hence enhancing the inhibition activity with the active site of the COX-1 enzyme. All the tested compounds have more negative Gibbs free, electrostatic, and total intermolecular energies than the standard inhibitor ASA. These results indicate that, all the tested sultams are potent anti-inflammatory drugs as compared to standard inhibitors. Finally, the chemical properties and the quantum factors of synthesized sultams were calculated based on density functional theory (DFT) to predict reactivity, and then correlated with the experimental data. Ester 3f showed the lowest ionization potential and lowest energy gap (Egap = 7.5691 eV), which was correlated with its cytotoxic activity. Furthermore, the spatial electron distribution of HOMO, LUMO were computed and it clearly indicates the electron donation ability of all the tested compounds.

Effect of a single water molecule on ˙CH2OH + 3O2 reaction under atmospheric and combustion conditions.

The hydroxymethyl (˙CH2OH) radical is an important intermediate species in both atmosphere and combustion reaction systems. The rate coefficients for ˙CH2OH + 3O2 and (˙CH2OH + 3O2 (+H2O)) reactions were calculated using the Rice-Ramsperger-Kassel-Marcus (RRKM)/master equation (ME) simulation and canonical variational transition state theory (CVT) between the temperature range of 200 to 1500 K based on the potential energy surface constructed using CCSD(T)//ωB97XD/6-311++G(3df,3pd). The results show that ˙CH2OH + 3O2 leads to the formation of CH2O and HO2 at temperatures below 800 K, and goes back to reactants at high temperature (>1000 K). When a water molecule is added to the reaction, the formation of CH2O and HO2 is favored at all temperatures. The calculated rate coefficient for the ˙CH2OH + 3O2 (2.8 × 10-11 cm3 molecule-1 s-1 at 298 K) is in good agreement with the previous experimental values (∼1 × 10-11 cm3 molecule-1 s-1 at 298 K). The rate coefficients for the water-assisted reaction (2.4 × 10-16 cm3 molecule-1 s-1 at 1000 K) is at least 3-4 orders of magnitude smaller than the water-free reaction (6.2 × 10-12 cm3 molecule-1 s-1 at 1000 K). This result is consistent with the similar types of reaction system. Our calculations also predict that the effect of a single water molecule favors the formation of CH2O in the combustion condition. However, the water-free reaction favors the formation of CH2O in the atmospheric condition. The current study helps to understand how a single water molecule changes the reaction mechanism and chemical kinetic behaviour under atmospheric and combustion conditions.

Novel photoresponsive cyclicparaphenylenediazenes: structure, strain energy, cis-trans isomerization, and electronic properties.

A series of cis-trans isomers of cyclicparaphenylenediazenes (CPPDs) have been designed to explore their potential applications in solar thermal fuels and photoswitchable devices. In this work, three isomers of cis-trans-[3]CPPD, seven isomers of cis-trans-[4]CPPD, eleven isomers of cis-trans-[5]CPPD, and sixteen isomers of cis-trans-[6]CPPD have been proposed using density functional theory (DFT) at the B3LYP/6-31+G(d,p) level of theory. The stability of these CPPDs has been quantified by the homodesmotic reaction approach. Strain energies (SE) indicate that 3-cct, 4-ctct-anti, 5-cctct-anti, and 6-cttttc-anti are stable molecules in their respective CPPDs. The SE and heats of formation of cis-trans-CPPDs were also compared with those of all-cis-CPPDs and all-trans-CPPD isomers. The calculations suggest that cis-trans-CPPDs are more stable than all-cis and all-trans-CPPDs. The SE and also suggest that 3-cct, 4-ctct-anti, 5-cctct-anti, and 6-cttttc-anti are important candidates for laboratory test. The calculated highest occupied molecular orbital (HOMO) to the lowest unoccupied molecular orbital (LUMO) energy gaps of cis-trans-CPPDs indicate that these oligomers are potential materials for the construction of solar cells. Time-dependent (TD) DFT calculations of CPPDs show a characteristic peak in the range of 450 nm to 600 nm, which is consistent with previous studies. The predicted structures, and thermochemical and electronic properties can be a good starting point for the synthesis of CPPD-based photoswitchable and solar fuel cell devices.

Catalytic effect of a single water molecule on the OH + CH2NH reaction.

In recent work, there has been considerable speculation about the atmospheric reaction of methylenimine (CH2NH), because this compound is highly reactive, soluble in water, and sticky, thus posing severe experimental challenges. In this work, we have revisited the kinetics of the OH + CH2NH reaction assisted by a single water molecule. The potential energy surfaces (PESs) for the water-assisted OH + CH2NH reaction were calculated using the CCSD(T)//BH&HLYP/aug-cc-pVTZ levels of theory. The rate coefficients for the bimolecular reaction pathways CH2NHH2O + OH and CH2NH + H2OHO were computed using canonical variational transition state theory (CVT) with small curvature tunneling correction. The reaction without water has four elementary reaction pathways, depending on how the hydroxyl radical approaches CH2NH. In all cases, the reaction begins with the formation of a single pre-reactive complex before producing abstraction and addition products. When water is added, the products of the reaction do not change, and the reaction becomes quite complex, yielding four different pre-reactive complexes and eight reaction pathways. The calculated rate coefficient for the OH + CH2NH (water-free) reaction at 300 K is 1.7 × 10-11 cm3 molecule-1 s-1 and for OH + CH2NH (water-assisted), it is 5.1 × 10-14 cm3 molecule-1 s-1. This result is similar to the isoelectronic analogous reaction OH + CH2O (water-assisted). In general, the effective rate coefficients of the water-assisted reaction are 2∼3 orders of magnitude smaller than water-free. Our results show that the water-assisted OH + CH2NH reaction cannot accelerate the reaction because the dominated water-assisted process depends parametrically on water concentration. As a result, the overall reaction rate coefficients are smaller.

Comparison of Three Isoelectronic Multiple-Well Reaction Systems: OH + CH2O, OH + CH2CH2, and OH + CH2NH.

Methylenimine (CH2NH) has been predicted to be a product of the atmospheric photo-oxidation of methylamine, but its atmospheric reactions have not been measured. In this paper, we report potential energy surfaces (PESs) and rate constants for OH + CH2NH and its isoelectronic analogues OH + CH2O and OH + CH2CH2, which are more fully understood. The PESs were computed using the BHandHLYP/aug-cc-pVTZ and CCSD(T)/aug-cc-pVTZ levels of theory. Canonical variational transition state theory and Rice-Ramsperger-Kassel-Marcus and master equation modeling were used to calculate temperature- and pressure-dependent rate constants, with particular emphasis on the OH + reactant entrance channels and the effects of prereactive complexes. The computed results are in reasonable agreement with experimental data where they can be compared and also with the results of previous theoretical calculations. The results show that to some extent OH radicals both add to the carbon center double bond in CH2NH and abstract methylene hydrogen atoms, as in the OH + CH2O and OH + CH2CH2 reactions, respectively, but the dominant pathway is abstraction of the hydrogen from N-H. The computed rate constants are suitable for both atmospheric and combustion modeling.

Photoionization mass spectrometric measurements of initial reaction pathways in low-temperature oxidation of 2,5-dimethylhexane.

Product formation from R + O2 reactions relevant to low-temperature autoignition chemistry was studied for 2,5-dimethylhexane, a symmetrically branched octane isomer, at 550 and 650 K using Cl-atom initiated oxidation and multiplexed photoionization mass spectrometry (MPIMS). Interpretation of time- and photon-energy-resolved mass spectra led to three specific results important to characterizing the initial oxidation steps: (1) quantified isomer-resolved branching ratios for HO2 + alkene channels; (2) 2,2,5,5-tetramethyltetrahydrofuran is formed in substantial yield from addition of O2 to tertiary 2,5-dimethylhex-2-yl followed by isomerization of the resulting ROO adduct to tertiary hydroperoxyalkyl (QOOH) and exhibits a positive dependence on temperature over the range covered leading to a higher flux relative to aggregate cyclic ether yield. The higher relative flux is explained by a 1,5-hydrogen atom shift reaction that converts the initial primary alkyl radical (2,5-dimethylhex-1-yl) to the tertiary alkyl radical 2,5-dimethylhex-2-yl, providing an additional source of tertiary alkyl radicals. Quantum-chemical and master-equation calculations of the unimolecular decomposition of the primary alkyl radical reveal that isomerization to the tertiary alkyl radical is the most favorable pathway, and is favored over O2-addition at 650 K under the conditions herein. The isomerization pathway to tertiary alkyl radicals therefore contributes an additional mechanism to 2,2,5,5-tetramethyltetrahydrofuran formation; (3) carbonyl species (acetone, propanal, and methylpropanal) consistent with ß-scission of QOOH radicals were formed in significant yield, indicating unimolecular QOOH decomposition into carbonyl + alkene + OH.

Reaction pathways for the thermal decomposition of methyl butanoate.

In recent years, biodiesel fuels, consisting of long-chain alkyl (methyl, ethyl, propyl) esters, have emerged as viable alternatives to petroleum-based fuels. From a combustion chemistry standpoint, there is great interest in developing accurate reaction models for these new molecules that can be used to predict their behaviors in various regimes. In this paper, we report a detailed study of the unimolecular decomposition pathways of methyl butanoate (MB), a short-chain ester that contains the basic chemical structure of biodiesel fuels. Using ab initio/DFT methods, we identified five homolytic fissions of C-C and C-O bonds and five hydrogen transfer reactions. Rate constants were determined using the G3B3 theory coupled with both variational transition state theory and Rice-Ramsperger-Kassel-Marcus/master equation simulations with hindered rotation corrections. Branching ratios in the temperature range 1500-2200 K indicate that the main pathway for thermal decomposition of MB is the reaction CH3CH2CH2C(═O)OCH3 → C2H5 + CH2C(═O)OCH3. The results, in terms of reaction pathways and rate constants, can be used for future development of mechanisms for long alkyl-chain esters.