Free Alkyl Research Articles

Inhibitory effects of cold plasma-activated water on the generation of advanced glycation end products and methylimidazoles in cookies and mechanistic evaluation using electron paramagnetic resonance

The inhibitory effects of cold plasma-activated water (PAW) on the formation of AGEs and methylimidazoles in cookies was examined. The results showed that different PAW (parameters: 50 W–50 s, 50 W–100 s, 50 W–150 s, 100 W–50 s, 100 W–100 s, and 100 W–150 s) reduced the contents of AGEs and methylimidazoles, in which the maximum inhibition rates were 47.38% and 40.17% for free and bound AGEs and 44.16% and 40.31% for free and bound methylimidazoles, respectively. Moreover, the mechanisms associated with the elimination of carbonyl intermediates and free radicals was determined by electron paramagnetic resonance (EPR) and high performance liquid chromatography-ultraviolet/visible absorption detector (HPLC-UV/Vis). The results showed the quenching of total free radicals, alkyl free radicals, and HO· by PAW, leading to the suppression of glyoxal and methylglyoxal intermediates. These findings support PAW as a promising agent to enhance the safety of cookies.

Photothermal-triggered release of alkyl radicals hydrogel via versatile carbon dots chelating Ag+ and its synergistic anti-bacterial and biofilm activities

Staphylococcus aureus has become one of the most common pathogens in clinical tissue infection, and it is easy to form biofilm. Incomplete removal of biofilms often leads to recurrent infections, and more serious is the possibility of bacteria developing drug resistance. Therefore, the effective eradication of refractory biofilms is essential. Herein, a temperature-sensitive hydrogel was prepared by doping the photothermal carbon dots (PTCDs) chelated by Ag+, and the AIPH which could produce alkyl radicals in response to heat into the thermodissolved gelatin. Under the irradiation of 660 nm laser, the PTCDs generated heat to dissolve the hydrogel, and promoted chelation of silver ions in PTCDs for chemical sterilization. Meanwhile, the heat generated by the PTCDs induced the 2,2′-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH) to produce alkyl free radical sterilization, achieving the purpose of photothermal/thermodynamic/chemical synergistic to kill Staphylococci aureus and destroy its biofilm. Therefore, the biocompatible PTCDs@Ag-AIPH hydrogel proposed in this study was a promising composite that could eliminate biofilms and promoted wound healing, showing good potential in future biomedical applications.

Evolution of pore structure and changes in oxidation characteristics of coal after heating freezing treatment

To study the spontaneous combustion characteristics of preheated coal treated by liquid nitrogen (LN2), surface structure test, thermal analysis experiment and chemical characteristic analysis experiment were used to study the change characteristics of surface structure, oxidation characteristic and chemical structure of coal under the action of LN2 quenching. The results showed that with the increase of preheating temperature, the fractal dimension, specific surface area, pore volume and average pore diameter of the LN2 treated coal (quenched-coal) increase. With the increase of preheating temperature, under the oxidation condition, the CO and CO2 produced at ST of 230 ℃ are 1.19 times and 1.21 times higher than those at ST of 70 ℃. The CO/CO2 emission of quenched-coal is significantly increased, and the secondary oxidation capacity is stronger. Due to the more developed pore cracks of coal under pyrolysis and quenching conditions, the natural characteristics of coal are stronger. The oxygen adsorption capacity and apparent activation energy of pyrolysis coal in the stageⅠ affected by LN2 are stronger. Oxidized coal shows stronger oxidation and heat release ability in the stageⅡ under the action of LN2, resulting in higher apparent activation energy in this endothermic stage. The addition of LN2 blocked the oxidation reaction of preheated coal and sealed the structure of -C = O, –COOH and –OH. The bridge bond –CH2- structure of pyrolysis coal is further destroyed, and the ratio of –CH2/–CH3 is reduced. The increase of alkyl free radicals in pyrolysis coal and alkyl oxygen free radicals in oxidation coal accelerates the spontaneous combustion oxidation of coal. The research results have important guiding significance for the occurrence and prevention of coal reignition disaster after LN2 fire quenching.

Energy-Transfer-Enabled Radical Acylation Using Free Alkyl Boronic Acids through Photo and NHC Dual Catalysis

Energy-Transfer-Enabled Radical Acylation Using Free Alkyl Boronic Acids through Photo and NHC Dual Catalysis

Theoretical determination of the standard enthalpies of formation of alkyl radicals using the concept of a complete set of homodesmotic reactions

The complete sets of homodesmotic reactions (HDR) for 107 acyclic alkyl free radicals С4-С9 of normal and branched structure were constructed using the graph-theoretic representation and analysis of a tested compound. The absolute enthalpies of the studied compounds and HDR reference structures were calculated using the M062X/cc-pVTZ level of theory. Based on these data, the thermal effects of HDRs were calculated and then applied to determine the standard enthalpies of formation of the studied radicals using the known enthalpies of formation of reference structures. The dissociation energies of BDE C–H and C–CH3 bonds were also calculated. The effect of radical structure on the BDE value is discussed, and a new effect of stabilization of the radical center in the skewed conformation of free radical is established; this effect has not been previously described in the scientific literature.

Synthesis of 1,4‐Dicarbonyl Compounds via Visible‐Light‐Induced Decarboxylative Radical Cascade Reactions

AbstractWe herein report a method for the synthesis of 1,4‐dicarbonyl compounds using light‐activated electron donor‐acceptor (EDA) complexes. This multi‐component reaction involves the photoactivation of EDA complexes formed by carboxylic acid derivatives, triphenylphosphine, and sodium iodide, resulting in single‐electron reduction. The subsequent decarboxylation fragmentation leads to the formation of nucleophilic alkyl free radicals, which can undergo sequential radical coupling reactions with electron‐deficient and electron‐rich olefins. This method has been successfully applied to various aliphatic carboxylic acid derivatives, including tertiary, secondary, and primary ones, as well as multiple types of electron‐deficient olefins and enol silyl ethers. The entire process is conducted under mild conditions, indicating its potential for the synthesis of valuable synthetic compounds.

Synthesis, characterization and application of high sulfur content polymeric materials from fatty acids

A new series of high sulfur content polymers containing various amounts of fatty acids (oleic acid (OA), linoleic acid (LA) and linolenic acid (LnA)) was synthesized via inverse vulcanization method and characterized successfully. In particular, the effect of double bonds and free alkyl chains on polysulfur copolymers has been investigated systematically by using OA with one double bond, LA with two double bonds and LnA with three double bonds. The copolymers with functional carboxylic acid groups are soluble in common organic solvents, processable and electroactive. Also, the usage of the copolymers was tested in the removal of methylene blue and as a cathode material in LiS battery. Results showed that the polymers can be a potential material for use in dye removal.

Interplay of diruthenium catalyst in controlling enantioselective propargylic substitution reactions with visible light-generated alkyl radicals

Transition metal-catalyzed enantioselective free radical substitution reactions have recently attracted attention as convenient and important building tools in synthetic chemistry, although construction of stereogenic carbon centers at the propargylic position of propargylic alcohols by reactions with free radicals remains unchallenged. Here we present a strategy to control enantioselective propargylic substitution reactions with alkyl radicals under photoredox conditions by applying dual photoredox and diruthenium catalytic system, where the photoredox catalyst generates alkyl radicals from 4-alkyl-1,4-dihydropyridines, and the diruthenium core with a chiral ligand traps propargylic alcohols and alkyl radicals to guide enantioselective alkylation at the propargylic position, leading to high yields of propargylic alkylated products containing a quaternary stereogenic carbon center at the propargylic position with a high enantioselectivity. The result described in this paper provides the successful example of transition metal-catalyzed enantioselective propargylic substitution reactions with free alkyl radicals.

The regularity of heat-induced free radicals generation and transition of camellia oil

In this study, the radicals formed in camellia oil upon a heating process were identified and quantified using Electron Spin Resonance (ESR) spectroscopy coupled with spin-trapping technique. PBN and DMPO were served as spin traps. The total amounts of free radicals of heated camellia oil showed an increasing trend with the extension of heating time at 140 °C, 150 °C and 160 °C. In accordance with hyperfine splitting constants (aN, aH) ─ the crucial parameter for identifying free radical species ─ of free radical, it was definitely confirmed that alkyl, alkoxyl, oxygen-centered and DMPO oxidate free radicals were present in heated camellia oil. A free radical transition pathway was proposed that alkyl free radical is initially generated, then, alkyl peroxy free radical is subsequently generated in the presence of oxygen which eventually shifts into alkoxyl free radical by means of an intermediate formed from H-capture reaction of alkyl peroxy free radical.

Unraveling inhibitory effects of Alpinia officinarum Hance and curcumin on methylimidazole and acrylamide in cookies and possible pathways revealed by electron paramagnetic resonance

The synchronous mitigative effects of Alpinia officinarum Hance (AOH) and curcumin on the generation of methylimidazole and acrylamide in cookies were investigated. Possible mechanisms related to quenching free radicals, reducing lipid oxidation and eliminating carbonyl intermediates were explored by electron paramagnetic resonance (EPR) and HPLC. The total methylimidazole and acrylamide contents raised with an increase in heating temperature and time, and reached a maximum at 200 °C for 11 min. AOH and curcumin reduced methylimidazole and acrylamide simultaneously; the maximum inhibition rates for methylimidazole and acrylamide were 51.55% (0.015% curcumin) and 73.66% (1.5% AOH). Alkyl free radicals and HO· were proved to be the critical free radicals for methylimidazole and acrylamide, AOH and curcumin quenched these radicals in a dose-dependent manner. The lipid oxidation, active carbonyl intermediates glyoxal, methylglyoxal, and acrylaldehyde were also reduced by AOH and curcumin simultaneously, which may be resulted from the quenching of free radicals.

Ginger and curcumin can inhibit heterocyclic amines and advanced glycation end products in roast beef patties by quenching free radicals as revealed by electron paramagnetic resonance

This study investigated the inhibitory effects of ginger and curcumin on the formation of free and bound heterocyclic amines (HAs)1 and advanced glycation end products (AGEs) in roast beef patties. The underlying mechanism related to quenching free radical, alleviating lipid peroxidation and scavenging carbonyl intermediates was explored by electron paramagnetic resonance (EPR) and UPLC-MS/MS. Ginger (0.5%, 1.0%, 1.5%) and curcumin (0.005%, 0.010%, 0.015%) dose-dependently inhibited free and bound HAs and AGEs simultaneously. The maximum inhibition rates for free and bound HAs were 59.97% (0.015% curcumin) and 27.42% (1.5% ginger), and those for free and bound AGEs were 71.57% and 35.64% (1.5% ginger). EPR result indicated alkyl free radical and 1O2 were the pivotal free radicals for HAs and AGEs, and ginger and curcumin also dose-dependently reduced these radicals. Lipid peroxidation, active carbonyl intermediates-phenylacetaldehyde, glyoxal, and methylglyoxal were also inhibited by ginger and curcumin in a dose-dependent manner, probably due to quenching of free radical.

Mitigative capacity of Kaempferia galanga L. and kaempferol on heterocyclic amines and advanced glycation end products in roasted beef patties and related mechanistic analysis by density functional theory

The capacity of Kaempferia galanga L. (KG) and kaempferol to mitigate the formation of free and bound heterocyclic amines (HAs) and advanced glycation end products (AGEs) in roast beef patties was explored. Electron paramagnetic resonance (EPR) and density functional theory (DFT) were used to reveal the possible mechanisms involved in quenching the free radicals. KG (0.5%, 1.0%, 1.5%) and kaempferol (0.005%, 0.010%, 0.015%) reduced HAs and AGEs in a dose-dependent manner. Alkyl free radical, HOO·, and 1O2 were critical to the formation of HAs, and 1O2 was pivotal to AGEs. They were quenched by KG and kaempferol in a dose-dependent manner. DFT indicated that the 3-OH group of kaempferol was most pivotal and quenched the HOO· mainly via H-atom transfer. The active carbonyl intermediates phenylacetaldehyde, glyoxal, and methylglyoxal can also be reduced by KG and kaempferol in a dose-dependent manner, which may be result from the quenching of free radicals.

Mitochondrial targeted melanin@mSiO2 yolk-shell nanostructures for NIR-Ⅱ-driven photo-thermal-dynamic/immunotherapy

The challenge of photothermal therapy (PTT) clinical transformation is the limited penetration depth of laser light and the general concern of using synthetic photothermal nanomaterials. Hence, it is of great significance to develop combined cancer therapies based on NIR-II photothermal agents from natural materials. Herein, natural melanin nanoparticles from cuttlefish ink coated with large pore mesoporous SiO2 were developed to load azodiisobutylimidazoline hydrochloride (AIPH@MS). After modification with (3-carboxypropyl) triphenylphosphonium bromide (CTPP), AIPH@MS-CTPP nanoparticles showed enhanced retention in the tumor site and were further delivered to thermally susceptible mitochondria. Under 1064 nm laser irradiation, hyperthermia produced by melanin not only directly leads to cell death but also promotes AIPH release to generate oxygen-independent alkyl free radicals, which could further attack tumor cells. The collaboration of the photothermal effect of melanin and thermodynamic therapy of AIPH could induce a local antitumor immune response and effectively reprogram tumor-associated macrophages from the M2 to M1 phenotype. In combination with anti-PD-1 immune checkpoint blockade, the paralyzed immune system was awakened to inhibit and eliminate secondary metastatic tumors. The NIR-II-driven treatment in this paper can achieve energy conversion processes from NIR-II light to thermal energy and then to chemical energy to perform photothermal-dynamic therapy and immunotherapy. This will overcome the high side effects and insufficient antitumor immune response of PTT and provide a strategy for effective and mild antitumor therapy with clinically approved laser power and safe nanotechnology.

Forced Solid-State Oxidation Studies of Nifedipine-PVP Amorphous Solid Dispersion.

In the present study, the oxidative degradation behavior of nifedipine (NIF) in amorphous solid dispersions (ASDs) prepared with poly(vinyl pyrrolidone) (PVP) with a short (K30) and a long (K90) chain length was investigated. The ASDs were prepared via dry ball-milling and analyzed using Fourier transform infrared (IR) spectroscopy, X-ray scattering, and differential scanning calorimetry. The ASDs were exposed to accelerated thermal-oxidative conditions using a pressurized oxygen headspace (120 °C for 1 day) and high temperatures at atmospheric pressure (60-120 °C for a period of 42 days). Additionally, solution-state oxidative degradation studies showed that pure NIF degrades to a greater extent than in the presence of PVP. Electronic structure calculations were performed to understand the impact of drug-polymer intermolecular interactions on the autoxidation of drugs. While no drug degradation was observed in freshly prepared ASD samples, alkyl free radicals were detected via electron paramagnetic resonance (EPR) spectroscopy. The free radicals were found to be consumed to a greater extent by PVP K30- than PVP K90-based ASDs upon exposure to high oxygen pressures. This was consistent with the greater solid-state oxidative degradation of NIF observed in ASDs with PVP K30 than with PVP K90. As no drug recrystallization occurred during this study period, the lower glass-transition temperature and presumed greater molecular mobility of PVP K30 and its ASD as compared to the PVP K90 system appear to contribute to the greater drug degradation in PVP-K30-based ASDs. The extent and the rate of oxidative degradation were higher in the case of PVP-K30-based ASD as compared to that in PVP-K90-based ASD, and the overall degradation increased with an increase in temperature. IR spectral analysis of drug-polymer interactions supports the electronic calculations of the oxidation process. We infer that, apart from the initial free radical content, the difference in the extent of drug-polymer intermolecular interactions in ASDs and amorphous stabilization during the forced oxidation experiments contribute to the observed differences in the autoxidative reactivity of the drug in ASDs with different PVP chain lengths. Overall, the chemical degradation of NIF in ASDs with two PVP chain lengths obtained from accelerated solid-state oxidation studies was in qualitative agreement with that obtained from long-term (3 years) storage under ambient conditions. The study highlights the ability of accelerated processes to determine the oxidative degradation behavior of polymeric ASDs and suggests that the polymer chain length could factor into chemical as well as physical stability considerations.

Advances in free-radical alkylation and arylation with organoboronic acids.

Organoboronic acids act as carbon-centered radical precursors that are widely utilized to construct diverse C-C bonds. This review summarizes the advances in this field. The content is divided into four parts according to the different categories of coupling partners with organoboronic acids. The reaction conditions as well as the mechanisms are demonstrated in each part.

Tunable aggregation-induced emission, solid-state fluorescence, and mechanochromic behaviors of tetraphenylethene-based luminophores by slight modulation of substituent structure

Herein, we report the synthesis of two AIE-active tetraphenylethene-derived luminogens with diethylamino (TPEDA) or pyrrolidino group (TPEPL) as terminal substituents, and systematically investigate the influence of diethylamino and pyrrolidino groups as terminal substituents on their photophysical properties and mechanochromic behavior. Single-crystal structural analyses verified that the free alkyl chains of the diethylamino groups were beneficial to loosen the intermolecular stacking. They exhibited distinct luminescence behaviors in the aggregated state. Compared with TPEDA, TPEPL displayed a long-wavelength solid-state fluorescence due to the more extended π-conjugation system across its intermolecular packing structure. However, TPEDA exhibited mechanochromic behavior that manifested in a larger red-shift (25 ​nm), which was attributed to its looser stacking mode. The work not only presents a better understanding of structure-property relationship, but also offers a new method for modulating intermolecular stacking and developing mechanochromic materials.

Photoredox-catalyzed multicomponent Petasis reaction in batch and continuous flow with alkyl boronic acids

SummaryMulticomponent reactions (MCRs) are ideal platforms for the generation of a wide variety of organic scaffolds in a convergent and atom-economical manner. Many strategies for the generation of highly substituted and diverse structures have been developed and among these, the Petasis reaction represents a viable reaction manifold for the synthesis of substituted amines via coupling of an amine, an aldehyde and a boronic acid (BA). Despite its synthetic utility, the inherent drawbacks associated with the traditional two-electron Petasis reaction have stimulated continuous research towards more facile and tolerant methodologies. In this regard, we present the use of free alkyl BAs as effective radical precursors in this MCR through a single-electron transfer mechanism under mild reaction conditions. We have further demonstrated its applicability to photo-flow reactors, facilitating the reaction scale-up for the rapid assembly of complex molecular structures.

A near-infrared light-controlled, oxygen-independent radical generating nano-system toward cancer therapy.

Anti-tumor treatment based on free radicals is often inefficient in hypoxic tumors, mainly because of the oxygen-dependent generation mechanism of reactive oxygen species (ROS). Herein, we report an NIR laser-controlled nano-system that is capable of generating alkyl radicals in situ in an oxygen-independent approach. Hollow mesoporous Prussian blue nanoparticles (HPB NPs) were developed to co-encapsulate the azo initiator (AIBI) and 1-tetradecanol as the phase change material (PCM, melting point of ∼39 °C), obtaining the AP@HPB NPs. At normal body temperature, the PCM remained in the solid state to prevent the pre-leakage of AIBI. Upon NIR laser irradiation (808 nm) at the tumor site, AP@HPB NPs generated heat upon photothermal conversion, which melted the PCM to release AIBI and decomposed AIBI to produce toxicity free alkyl radicals under both normoxic and hypoxic conditions. The alkyl free radicals efficiently killed tumor cells by causing oxidative stress and damaging DNA. Meanwhile, NIR light-induced hyperthermia cooperated with free radicals to efficiently eradicate tumors. This study therefore provides a promising strategy toward oxygen-independent free radical therapy, especially for the treatment of hypoxic tumors.

Mechanism of Ni-Catalyzed Oxidations of Unactivated C(sp3)-H Bonds.

The Ni-catalyzed oxidation of unactivated alkanes, including the oxidation of polyethylenes, by meta-chloroperbenzoic acid (mCPBA) occur with high turnover numbers under mild conditions, but the mechanism of such transformations has been a subject of debate. Putative, high-valent nickel-oxo or nickel-oxyl intermediates have been proposed to cleave the C-H bond, but several studies on such complexes have not provided strong evidence to support such reactivity toward unactivated C(sp3)-H bonds. We report mechanistic investigations of Ni-catalyzed oxidations of unactivated C-H bonds by mCPBA. The lack of an effect of ligands, the formation of carbon-centered radicals with long lifetimes, and the decomposition of mCPBA in the presence of Ni complexes suggest that the reaction occurs through free alkyl radicals. Selectivity on model substrates and deuterium-labeling experiments imply that the m-chlorobenzoyloxy radical derived from mCPBA cleaves C-H bonds in the alkane to form an alkyl radical, which subsequently reacts with mCPBA to afford the alcohol product and regenerate the aroyloxy radical. This free-radical chain mechanism shows that Ni does not cleave the C(sp3)-H bonds as previously proposed; rather, it catalyzes the decomposition of mCPBA to form the aroyloxy radical.

Rheological properties and crystallization behavior of modified polylactic acid using lauroyl peroxide and glycidyl methacrylate

AbstractThe molecular structure of polylactic acid (PLA) was modified by lauroyl peroxide (LP) as an alkyl free radical and glycidyl methacrylate (GMA) as a reactive co‐monomer. We investigated the effect of different preparation methods, that is, the melt and solution, on the structure and physical and mechanical properties of glycidyl methacrylate grafted polylactic acid (PLA‐g‐GMA). The Fourier transformed infrared spectroscopy (FTIR) was implemented to characterize the final products in order to confirm that GMA was successfully grafted onto PLA. The gel permeation chromatography showed that the molecular weight and polydispersity of the modified PLA were increased by grafting. However, by varying other parameters such as the reaction time and the LP and GMA concentrations, we observed that the resulting products from the melt method are richer in the rheological properties compared with those properties from the solution method. This is due to the different molecular weights resulted from the either preparation methods. From the DSC characteristics of PLA‐g‐GMA samples, the crystallization degree of the samples prepared from the melt method is greater than that of the solution method. Meanwhile, the cold crystallization for the PLA‐g‐GMA samples derived from the solution method occurs at higher temperatures compared with the cold crystallization of the samples resulted from the melt method.