Ring-opened Products Research Articles

Oxidation of isoprothiolane by ozone and chlorine: Reaction kinetics and mechanism

Isoprothiolane (IPT) was one of the most commonly used pesticides around the world. It was reported to be the highest concentration and frequency of detection of 13 most commonly used pesticides in Mekong Delta recently. The oxidation degradation kinetic of ozone and chlorine with IPT and the identification of the degradation products was investigated in this research. The results showed that both ozone and chlorine oxidized IPT rapidly under typical water treatment condition, and that both reactions followed second order reaction kinetics. The ozone reaction rates exhibited no pH dependence with the rate constant of 247.1 (±11.0) M−1s−1 at 25 °C, whereas chlorine reaction rates increased dramatically with decreasing pH. The rate constant for hypochloric acid was 73.3 (±3.1) M−1s−1 at 25 °C, while the reaction of hypochlorite was negligible. The degradation products by chlorine and ozone were identified by LC-MS/MS and the reaction pathways were proposed. The thioether and the carbon-carbon double bond in IPT were the reactive sites during chlorine and ozone oxidation. The thioether group was oxidized into sulfoxide and further sulfone group, and the carbon-carbon double bone were cleaved to form diisopropyl ester of malonic acid, diisopropyl ester of tartronic acid and diisopropyl ester of ketomalonic acid monohydrate. Compared to ozone reaction, it was more complicated for chlorine reaction, which yielded chlorine substituted, hydroxylated and dithiolane ring-opening products.

Development of N-Cyclopropylanilines to Probe the Oxidative Properties of Triplet-State Photosensitizers.

Anilines have been shown to be especially susceptible to single-electron oxidation by excited triplet-state photosensitizers (3sens*), and thus, are good potential candidates to probe the oxidative properties of triplet-state chromophoric dissolved organic matter (3CDOM*). However, steady-state experiments tend to underestimate their rate of oxidation by 3CDOM* due to radical cation quenching (i.e., aniline•+ → aniline) by antioxidant moieties present in DOM. We envisioned the potential utility of N-cyclopropylaniline (CPA) to overcome this limitation, as it is known to undergo spontaneous, irreversible cyclopropyl ring-opening after an initial single-electron oxidation. To test this, first a set of CPA analogs was synthesized and then paired with a model sensitizer and antioxidant, or various DOM isolates, to examine their reactivity and susceptibility to antioxidant quenching during steady-state photolysis experiments. Next, time-resolved measurements of CPA and CPA analog oxidation were obtained by laser flash photolysis through direct observation of 3sens* and radical cations of CPA and CPA analogs. Finally, CPA photolysis products were isolated by semi-preparative high-performance liquid chromatography and identified by nuclear magnetic resonance spectroscopy. Outcomes of this work, including oxidation bimolecular rate constants of CPA and CPA analogs (∼9 × 108 to 4 × 109 M-1 s-1), radical cation lifetimes of CPA and its analogs (140-580 ns), and identified ring-opened products, support the usefulness of cyclopropylanilines as single-electron transfer probes in photosensitized aqueous solutions.

The Addition of a Cyclopropyl Alkyne to an Asymmetrically-Substituted Disilene: A Mechanistic Study

The addition of (2-ethynyl-3-methoxy-2-methylcyclopropyl)benzene to Tip2Si═SiTipPh, a disilene with an asymmetric substitution pattern, was investigated. The regiochemistry of the ring-opened products indicates a stepwise mechanism with a biradical intermediate. The results are consistent with those obtained in similar experiments with symmetrically substituted disilenes.

Method validation and preliminary pharmacokinetic studies on the new designer stimulant 3-fluorophenmetrazine (3-FPM).

Pharmaceutical research not only provides the basis for the development of new medicinal products but also for the synthesis of new drugs of abuse. 3-Fluorophenmetrazine (3-FPM), a fluorinated derivative of the anorectic phenmetrazine, was first patented in 2011 and appeared on the drug market in 2014. Though invented for potential medical purposes, pharmacokinetic data on this compound, crucial for interpreting forensic as well as clinical cases, are not available. Therefore, a liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method for the detection of 3-FPM in serum, urine, and oral fluid was developed, validated for urine and serum, and used to quantify 3-FPM in samples obtained during a controlled self-experiment. The method proved to be linear, selective and sufficiently sensitive. The limits of detection (LODs) were 0.1ng/mL, 0.2ng/mL, and 0.05ng/mL in serum, urine, and oral fluid. Inter-day precision and intra-day precision (RSD) in serum samples were below 6.3% and below 8.5%, respectively. The highest serum concentration (cmax ) of 210ng/mL was reached 2.5hours (tmax ) after ingestion. The elimination half-life and the volume of distribution were calculated to be approx. 8.8hours and 400L (5.3L/kg). 3-FPM could be detected in serum and urine up to 82hours and 116hours, respectively. It was still detected in the last oral fluid sample taken 55hours after ingestion. 3-FPM was mainly excreted unchanged. Main metabolic reactions were aryl-hydroxylation and N-hydroxylation. Interestingly, the product of oxidative ring opening (2-amino-1-(3-fluorophenyl)propan-1-ol) showed the largest window of detection in the self-experiment.

Thermal catalytic degradation of α-HBCD, β-HBCD and γ-HBCD over Fe3O4 micro/nanomaterial: Kinetic behavior, product analysis and mechanism hypothesis

The new persistent organic pollutant (POP), 1,2,5,6,9,10-hexabromocyclododecane (HBCD), has been widely detected in various environmental media and proved to be biotoxic. However, the research on catalytic degradation of HBCD is in its infancy. Herein, we examined the degradation of α-HBCD, β-HBCD and γ-HBCD, over Fe3O4 micro/nanomaterial at 200 °C. The pseudo-first-order kinetic rate constants were in the range of 0.04–0.15 min−1, with half-life values of 5–19 min. γ-HBCD is slightly less stable than β-HBCD, but both of them readily convert into α-HBCD, as consistent with the Gibbs free energies of isomers themselves. The four products containing pentabromocyclododecene, two isomers of tetrabromocyclododecene and 1,5,9-cyclododecatriene were detected by conventional GC–MS. Interestingly, a high-throughput non-target product detection were performed by ESI-FT-ICR-MS, where up to 59 types of intermediate products were determined. It is tentatively proposed that different types of bromine-removed products (C12H17Br5, C12H18Br4, C12H18, C12H19Br5, C12H24 and C12H19Br5O) and cyclododecane ring-opened products (C12H19Br7, C12H20Br6O and C12H20Br6) form via elimination reaction, nucleophilic substitution, hydrodebromination and addition reaction. Besides, most of the products that were detected contained oxygen. The average carbon oxidation state (OSc¯) of the products indicate that the oxidation reaction is the dominant reaction type. Deep oxidation products, such as small molecular organic acids (formic, acetic, propionic, and butyric acids) and gas-phase oxidation products (CO2 and CO) were further detected by ion chromatography and GC-FID, respectively. This study might provide an alternative technique for the low-cost treatment of HBCD waste.

Theoretical investigation on atmospheric oxidation of fluorene initiated by OH radical

Atmospheric oxidation of fluorene and its derivatives initiated by OH radicals was investigated theoretically with quantum chemical calculation methods [M06-2X/6-311++G(3df,2p)//M06-2X/6-311+G(d,p)]. It revealed that the OH addition pathways form hydroxyfluorene and ring-opening product dialdehyde while the H abstraction pathways lead to the formation of 9-fluorenone. Subsequent oxidation of 9-fluorenone has considerable potential to form dibenzo-p-dioxin and nitrofluorenone according to the present calculation results. The atmospheric lifetime of fluorene relative to the reactions with OH radicals is deduced to be 12.51 h based on the calculated overall rate constant (2.29 × 10−11 cm3 molecule−1 s−1) at 298 K and 1 atm. The oxidation products of fluorene in the atmosphere are generally more toxic and persistent. This work provides a comprehensive explanation for atmospheric oxidation processes of fluorene and facilitates clarifying its environmental risks.

Pyrimidine Ring-Opened Product from Oxidative DNA Damage of 5-Formyl-2'-deoxyuridine.

After thymidine (dT) was treated with a Fenton-type reagent and further incubated for a long period (6 days) under physiological conditions (37 °C, pH 7.4), a new product, named dT*, was detected by HPLC in addition to the free thymine base and the known oxidative dT damage, 5-formyl-2'-deoxyuridine (f5dU). dT* was found to be formed from f5dU. The structure of dT* was determined to be 3-amino-2-carbamoyl-2-propenal-N3-2'-deoxyriboside, a pyrimidine ring-opened product from f5dU, on the basis of 1H- and 13C NMR analyses and mass spectra. From the model compound 1-methyl-5-formyluracil, a similar ring-opened product was formed after the incubation. dT* was also detected in DNA treated with a Fenton-type reagent or γ-rays, followed by the prolonged incubation. dT* will be a new promising marker of oxidative DNA damage. The possible role of this product in oxy-radical-induced mutagenesis is discussed.

Next-generation quantum theory of atoms in molecules for the ground and excited state of DHCL

The factors underlying two possible pathways for the Dihydrocostunolide (DHCL) photochemical ring-opening reaction were investigated; the first pathway returned to the ring-closed conformation of the reactant and the second pathway progressed to the ring-opened product. High-level multi-reference DFT methods were used to optimize the two pathways and the density was analyzed using QTAIM and the stress tensor. Oscillations in the chemical character of the fissile bond were found for the first pathway before and after the conical intersection that steered the reaction back to reactant. Conversely, this behavior was absent for the second pathway that led forward to the product.

Heterogeneous activation of peroxymonosulfate using Mn-Fe layered double hydroxide: Performance and mechanism for organic pollutant degradation

On account of high oxidation ability of sulfate radical-based advanced oxidation processes (AOPs), the eco-friendly catalysts for peroxymonosulfate (PMS) activation have received considerable attentions. Previous studies mainly focused on Cobalt-based catalyst due to its high activation efficiency, such as Co3O4/MnO2 and FeCo-layered double hydroxide (LDH), whereas Cobalt-based catalyst usually has serious risk to environment. To avoid this risk, MnFe-LDH was primarily synthesized in this research by simple co-precipitation and subsequently utilized as an effective catalyst for peroxymonosulfate (PMS) activation to degrade organic pollutants. The experimental results demonstrated that MnFe-LDH with a lower dosage (0.20 g/L) could efficiently activate PMS to achieve 97.56% removal of target organic pollutants Acid Orange 7 (AO7). The AO7 degradation process followed the pseudo-first-order kinetic well with an activation energy of 21.32 kJ/mol. The intrinsic influencing mechanism was also investigated. The quenching experiment and electron spin resonance (ESR) indicated that sulfate and hydroxyl radicals were produced by the effective activation of PMS by MnFe-LDH, resulting in a high rate of decolorization. The possible AO7 removal pathway in the constructed MnFe-LDH/PMS system was presented on the basis of UV–vis spectrum analysis and GC–MS, which suggested that the AO7 degradation was firstly initiated by breaking azo linkages, then generated phenyl and naphthalene intermediates and finally presented as ring-opening products. This effective MnFe-LDH/PMS system showed great application potential in the purification of wastewater contaminated by refractory organic pollutants.

Unveiling New Isomers and Rearrangement Routes on the C7H8+ Potential Energy Surface

The unimolecular reactions of C7H8+ radical cations are among those most studied by mass spectrometry, especially the rearrangement of toluene and cycloheptatriene molecular ions, which are directly connected to the formation of benzylium and tropylium cations. This study reveals important new isomers and isomerization pathways on the C7H8+ potential energy surface, through the application of gas-phase electronic photodissociation spectroscopy in conjunction with ab initio calculations. Presented are the first gas-phase vibrationally resolved electronic spectra of the o-isotoluene, norcaradiene, bicyclo[3.2.0]hepta-2,6-diene radical cations, and ring-opened products from cyclic C7H8+ species. The isomerization route from the norbornadiene radical cation to the toluene radical cation, which competes with isomerization to the bicyclo[2.2.1]hepta-2-ene-5-yl-7-ylium radical cation, is identified. Further, this work expands understanding of the C7H8+ potential energy surface by connecting spiro[2.4]hepta-4,6-diene and acyclic 1,2,4,6-heptatetraene radical cations, and confirms the important role of the o-isotoluene radical cation in the interconversion pathways of C7H8+ species.

Ultrafast ring-opening and solvent-dependent product relaxation of photochromic spironaphthopyran.

The ultrafast dynamics of unsubstituted spironaphthopyran (SNP) were investigated using femtosecond transient UV and visible absorption spectroscopy in three different solvents and by semi-classical nuclear dynamics simulations. The primary ring-opening of the pyran unit was found to occur in 300 fs yielding a non-planar intermediate in the first singlet excited state (S1). Subsequent planarisation and relaxation to the product ground state proceed through barrier crossing on the S1 potential energy surface (PES) and take place within 1.1 ps after excitation. Simulations show that more than 90% of the trajectories involving C-O bond elongation lead to the planar, open-ring product, while relaxation back to the S0 of the closed-ring form is accompanied by C-N elongation. All ensuing spectral dynamics are ascribed to vibrational relaxation and thermalisation of the product with a time constant of 13 ps. The latter shows dependency on characteristics of the solvent with solvent relaxation kinetics playing a role.

Reversible Multicolor Photochromism of Dihydroazulene Crystals.

The photochemical conversion of 1,8a-dihydroazulene-1,1-dicarbonitrile (DHA) to vinylheptafulvene (VHF) is a positive T-type photoswitch that is well understood in solution, but has not been explored in the solid state. Upon excitation with UV light, DHA is converted into VHF in the solid state, with a distinct color change from yellow to deep-red, and retention of crystallinity. The structure of the ring-opened product was assigned to syn-VHF using variable-temperature infrared spectroscopy, and determined by X-ray photodiffraction in a crystal enriched with the product by two-photon excitation. A radical pathway becomes an observable photoreaction channel at low temperatures, and includes a strongly colored, short-lived diradical intermediate.

Ring Opening of Naphthene Hydrocarbons under Conditions of Thermal and Microwave Heating

A comparative study of the activity and selectivity of monometallic Ir-containing catalysts in ring opening reactions under conditions of thermal and microwave heating is performed using the example of cyclohexane. The hydrogenolysis of cyclohexane is shown to be possible with microwave activation. It is found that upon microwave heating, iridium-containing catalysts supported on titanium oxide and activated carbon allow 60% selectivity to be reached with respect to ring opening products at 30% conversion of the initial cyclohexane.

Photochemical Aging of Guaiacol by Fe(III)–Oxalate Complexes in Atmospheric Aqueous Phase

Fe(III)-oxalate complexes are likely abundant in clouds, fogs and aerosol water. They are photoreactive and can act as an important source of reactive oxygen species (·OH, H2O2 and HO2·) in tropospheric aqueous phases. Although the mechanisms involved in ferrioxalate photolysis have been investigated extensively, few kinetic and mechanistic information is available on the aging of dissolved organic compounds by this photochemical system. In this work, the Fe(III)-oxalate mediated photooxidation of guaiacol (GUA), a model for phenolic compounds emitted from biomass burning, was investigated under typical pH conditions of the atmospheric water. The effect of Fe(III) concentration, oxalate concentration and pH on the photooxidation of GUA was studied in detail. Our results revealed that oxalate can inhibit the oxidation of GUA by Fe(III) under the dark condition. However, the iron-catalyzed photooxidation of GUA can be strongly promoted in the presence of oxalate due to the formation of photoactive Fe(III)-oxalate complexes. GUA was rapidly oxidized to form a number of polymeric, functionalized and open-ring products with low volatility. Detailed reaction pathways for the photooxidation of GUA by Fe(III)-oxalate complexes were proposed based on the results of high-resolution mass spectrometry. This work suggests that ferrioxalate photochemistry can play an important role in the transformation of dissolved organics in atmospheric aqueous phases.

Characterization of Ring-Opening Reaction of Succinimide Linkers in ADCs

A new class of highly potent biopharmaceutical drugs, antibody-drug conjugates (ADCs), has been proven to be clinically effective to treat oncologic diseases. ADCs contain 3 major components: the monoclonal antibody, cytotoxic drug, and chemical linker. THIOMAB™ drug conjugates and interchain-cysteine ADCs are common ADC platforms that apply thiol-maleimide chemistry via Michael addition to conjugate linker-drugs to cysteine residues. However, the resulting succinimide ring in the linker is susceptible to ring-opening reactions via hydrolysis, especially at high pH and elevated temperatures. Once the succinimide ring is opened, in vivo stability of the ADCs can be changed and the therapeutic activity will be altered. In this study, we investigated the impact of conjugation sites on succinimide ring opening for ADCs. A new methodology based on imaged capillary isoelectric focusing was developed to monitor the formation of succinimide ring-opened products. In addition, a reverse-phase high-performance liquid chromatography method was used to monitor site-specific ring-opening reactions. Our data confirmed that succinimide ring-opening rates in ADCs are conjugation-site dependent. With a good understanding of the conjugation site impact on final product’s stability, it is potentially feasible to modify ring-opening rates in vitro to achieve desirable in vivo stability and biological activity.

Comparative study on degradation of propranolol and formation of oxidation products by UV/H2O2 and UV/persulfate (PDS)

The frequent detection of propranolol, a widely used β-blocker, in wastewater effluents and surface waters has raised serious concern, due to its adverse effects on organisms. UV/hydrogen peroxide (UV/H2O2) and UV/persulfate (UV/PDS) processes are efficient in eliminating propranolol in various waters, but the formation of oxidation products in these processes, as well as the assessment of their toxicity, has not been systematically addressed. In this study, we identified and compared transformation products of propranolol produced by hydroxyl radical (•OH) and sulfate radical (SO4•-). The electrostatic attraction enhances the reaction between SO4•- and the protonated form of propranolol, while •OH shows non-selectivity toward both protonated and neutral propranolol species. The hydroxylation of propranolol by •OH occurs at either amine moiety or naphthalene group while SO4•- favors the oxidation of the electron-rich naphthalene group. Further oxidation by •OH and SO4•- results in ring-opening products. Bicarbonate and chloride exert no effect on propranolol degradation. The generation of CO3•- and Cl-containing radicals is favorable to oxidizing naphthalene group. The acute toxicity assay of Vibrio fischeri suggests that SO4•- generates more toxic products than •OH, while CO3•- and Cl-containing radicals produce similar toxicity as SO4•-. High concentrations of bicarbonate in UV/H2O2 increase the toxicity of treated solution.

Effect of the metallic particle size of supported Pt catalysts on methylcyclopentane hydrogenolysis: Understanding of the ring opening products distribution by a geometric approach

Hydrogenolysis of methylcyclopentane was studied in the presence of supported platinum catalysts, with particle sizes between 0.9 and 2.4 nm. The distribution of ring-opening products (n-hexane, 2-methylpentane, 3-methylpentane), which are virtually the only products at 573 K, mainly depended on the platinum particle size, with no effect of the methylcyclopentane conversion. This distribution was well described by the selective or non-selective mechanisms previously proposed in the literature except for the smallest particles (d < 1.5 nm), for which a very high yield in n-hexane was observed. A simplified model was developed combining a geometric approach, for counting the fraction of accessible surface of each superficial atom whatever the Pt particle size, to the knowledge of active sites for each product formation, as determined by DFT calculation. It was demonstrated that the sites responsible for n-hexane formation are corners and some edge sites, whereas 2-methylpentane and 3-methylpentane are formed on faces and a part of the edges.

An Efficient Synthesis of Oxazolidines by Tandem Ring‐Opening / Closing Reaction of Ts‐Aziridine Using Formic Acid

AbstractSynthesis of oxazolidines has been reported from aziridines by the reaction with formic acid and formaldehyde in neat conditions. We have also observed a regio‐selective nucleophilic ring opening of aziridines by HCOOH under same conditions in absence of formaldehyde where the HCOO− ion acts as a nucleophile. In this present method formic acid is not acting as reducing agent as classical organic reactions. The formic acid initially activates the aziridines whereas the formate group generated from formic acid acts as a nucleophile itself instead of the source of hydride ion affording the nucleophilic ring opening products. The synthesized formate ester was successfully hydrolyzed to the corresponding hydroxyl compound which is the key building block for the synthesis of heterocycles. Operational simplicity, mild and neat reaction conditions, broad substrates scope, good yields and uses of less expensive reagents are the notable advantages of the present procedures.

Conformer-related pathways in cycloaddition of vinylaziridines and alkynes catalyzed by rhodium(I)-complex

The conformer-related reaction pathways in the cycloaddition of vinylaziridines with alkynes were calculated using DFT methods. The calculated results reveal that the ring-opening products of vinylaziridines possess two different conformers with the specific sites available for coordination of alkynes. The formed alkyne-coordinated complexes results in the different CN bond addition intermediates. In the cycloaddition reaction catalyzed by [Rh(η6-C10H8)(COD)]SbF6, the intermediate needs an isomerization to yield the final [5 + 2] cycloaddition product. In the reaction catalyzed by [Rh(NBD)2]BF4, such an isomerization is dispensable to yield the final [3 + 2] cycloaddition product.

Photoinduced Heterocyclic Ring Opening of Furfural: Distinct Open-Chain Product Identification by Ultrafast X-ray Transient Absorption Spectroscopy.

The ultraviolet-induced photochemistry of five-membered heterocyclic rings often involves ring opening as a prominent excited-state relaxation pathway. The identification of this particular photoinduced mechanism, however, presents a challenge for many experimental methods. We show that femtosecond X-ray transient absorption spectroscopy at the carbon K-edge (∼284 eV) provides core-to-valence spectral fingerprints that enable the unambiguous identification of ring-opened isomers of organic heterocycles. The unique differences in the electronic structure between a carbon atom bonded to the oxygen in the ring versus a carbon atom set free of the oxygen in the ring-opened product are readily apparent in the X-ray spectra. Ultrafast ring opening via C-O bond fission occurs within ∼350 fs in 266-nm photoexcited furfural, as evidenced by fingerprint core (carbon 1s) electronic transitions into a nonbonding orbital of the open-chain carbene intermediate at 283.3 eV. The lack of recovery of the 1sπ* ground-state depletion in furfural at 286.4 eV indicates that internal conversion to the ground state is a minor channel. These experimental results, augmented by recent advances in the generation of isolated attosecond pulses at the carbon K-edge, will pave the way for probing ring-opened conical intersection dynamics in the future.