Supramolecular Radical Anions Triggered by Bacteria In Situ for Selective Photothermal Therapy

A supramolecular complex that can be selectively reduced to radical anions in situ by facultative anaerobic bacteria is reported. To this end, a water‐soluble bifunctional monomer bearing perylene diimide was synthesized, and its supramolecular complex with cucurbit[7]uril was fabricated on the basis of host–guest complexation, which could be reduced to forming radical anions in the presence of E. coli . It was found that this supramolecular complex could display different ability of generating radical anions by facultative anaerobic and aerobic bacteria in terms of their various reductive abilities. The selective antibacterial activity of the supramolecular complex could be realized by the photothermal performance of the radical anions under near‐infrared irradiation. It is anticipated that this method may lead to a novel bacteria‐responsive photothermal therapy to regulate balance of bacterial flora.     

Regioselective radical bromoallylation of allenes leading to 2-bromo-substituted 1,5-dienes

The regioselective radical bromoallylation of allenes proceeded efficiently in the presence of AIBN as a radical initiator to give 2-bromo-substituted 1,5-dienes in excellent yields. The addition of a bromine radical took place regioselectively onto the central carbon of allenes generating a stable allyl radical, which underwent addition/β-fragmentation reactions with allylbromides. The products could be further functionalized by Pd-catalyzed coupling reactions.     

Removal, recovery, and recycling of triarylphosphonium-supported tin reagents for various organic transformations

Phosphonium-supported tin reagents and catalysts were prepared and were shown to be effective in Stille couplings, radical dehalogenations, radical cyclizations, and carbonyl allylations. Not only could the tin residues be removed from the crude reaction mixture through a phase separation process but also they could be recovered and recycled.     

The study of stabilizer action modes by means of time-resolved techniques: Intermediate radical cations

In organic systems, radiation- and photo-induced electron transfer reactions result in the first step in the formation of radical cations. With pulse radiolysis and laser photolysis experiments radical cations of phenols could be indirectly characterized whereas radical cations of sterically hindered amines (HALS compounds) could be directly observed.     

Controlling the regiochemistry of radical cyclizations

This review describes the results of our recent studies on the control of the regiochemistry of radical cyclizations. N-vinylic alpha-chloroacetamides generally cyclized in a 5-endo-trig manner to give five-membered lactams, whereas 4-exo-trig cyclization occurred when the cyclized radical intermediates were highly stabilized by an adjacent phenyl or phenylthio group to afford beta-lactams. The 5-exo or 6-exo cyclization of aryl radicals onto the alkenic bond of enamides could be shifted to the corresponding 6-endo or 7-endo mode of cyclization by a positional change of the carbonyl group of enamides. The 6-endo- and 7-endo-selective aryl radical cyclizations were applied to radical cascades for the synthesis of alkaloids such as phenanthroindolizidine, cephalotaxine skeleton, and lennoxamine. The 5-exo-trig cyclization of an alkyl radical onto the alkenyl bond of enamides could also be shifted to the 6-endo mode by a positional change of the carbonyl group of enamides. The 6-endo- selective cyclization was applied to the radical cascade to afford a cylindricine skeleton. Other examples of controlling the regiochemistry of radical cyclizations and their applications to the synthesis of natural products are also discussed.     

Experimental and theoretical studies on radical trifluoromethylation of titanium ate and lithium enolates

The radical trifluoromethylation of Ti ate and Li enolates has been investigated by both experiments and density functional (UB3LYP/6-311+G//UB3LYP/6-31+G*) calculations. Radical CF3 addition to the enolates proceeds in a highly exothermic manner without significant reaction barriers in both Ti ate and Li enolates. There are two possible reaction paths after the addition of CF3 radical in the case of Ti ate enolate; one is the elimination of Ti(III) from the ketyl radical intermediate and the other is the direct reaction of the ketyl radical intermediate with CF3I. However, in the case of Li enolate, only the latter path is possible due to the high energy barrier of the elimination of the Li radical. This analysis provides an explanation of the experimental observation that the Li enolate could form the radical cycle efficiently but the Ti ate enolate could not. To make the radical cycle complete, I- has to be extracted from CF3I itself or the radical anion of CF3I. In the case of Li, formation of Li-I bond could be the driving force for the extraction of I- and regeneration of CF3 radical. However, Ti does not give exothermic Ti-I formation and thus regeneration of CF3 radical is less likely.     

On-line high-performance liquid chromatography-diode array detection-electrospray ionization-mass spectrometry-chemiluminescence assay of radical scavengers in Epimedium

An on-line analysis method for the simultaneous detection and identification of radical scavenging compounds in plant extracts was developed by combining HPLC with hydrogen dioxide radical scavenging and HPLC-DAD-MS-CL system. The structural identification and activity characteristics of various constituents could be rapidly achieved by the on-line assay of UV, MS and CL in one run. In 4 species of Epimedium studied 32 compounds, including phenolic acids, 8-isopentenyl-flavonoid glycosides and flavonoid glycosides containing a ortho-hydroxyl group, were identified by comparison with authentic standards and published mass data. Among these compounds, phenolic acids and flavonoid glycosides containing an ortho-hydroxyl group could obviously inhibit CL, which suggested their strong radical scavenging activity. These four species each exhibited different active properties, which might correlate to their respective quality. The results indicated that the on-line HPLC-DAD-MS-CL system would be a potential method to rapidly and sensitively screen radical scavengers in herbal medicines, and could display an integrated fingerprint based on different detectors.     

A computational study of remote C-H activation by amine radical cations: implications for the photochemical reduction of carbon dioxide

A computational study, using density functional theory calibrated against higher-level methods, has been undertaken to evaluate tertiary amines whose radical cations might lose hydrogen atoms from positions other than the alpha carbons. The purpose was to find photochemically activated reducing agents for carbon dioxide that could be regenerated in a separate photochemical reaction. The calculations have revealed two reactions that might be suitable for this purpose. In one, the nitrogen of the radical cation makes a bond to a remote carbon with simultaneous displacement of a hydrogen atom. In the other, a remote hydrogen atom is transferred to the nitrogen, thereby creating a distonic radical cation that can lose a hydrogen atom beta to the radical site. The latter reaction is found to be particularly favorable since it apparently involves a surface crossing that allows the amine radical cation and CO2 radical anion to transform smoothly to a ground-state formate ion and an alkene. A number of structural motifs are investigated for the amines. The lower ionization potential of aromatic amines, compared to their aliphatic analogues, is desirable in that it could permit the use of longer wavelength light to drive the reaction. However, a thermochemical cycle shows that the reduction in ionization potential must be matched by an increase in proton affinity of the amine if the intramolecular hydrogen transfer is to be exothermic. Most aromatic amines do not satisfy this criterion and, hence, would have to rely on the displacement reaction for hydrogen-atom release if they were to be used as renewable reagents for CO2 reduction. Examples of specific aromatic and aliphatic tertiary amines that should be suitable for the purpose are presented, and their relative merits and weaknesses are discussed.     

A Strategy for Controlling the Polymerizations of Thiyl Radical Propagation by RAFT Agents

The ability to extend the polymerizations of thiyl radical propagation to be regulated by existing controlled methods would be highly desirable, yet remained very challenging to achieve because the thiyl radicals still cannot be reversibly controlled by these methods. In this article, we reported a novel strategy that could enable the radical ring-opening polymerization of macrocyclic allylic sulfides, wherein propagating specie is thiyl radical, to be controlled by reversible addition–fragmentation chain transfer (RAFT) agents. The key to the success of this strategy is the propagating thiyl radical can undergo desulfurization with isocyanide and generate a stabilized alkyl radical for reversible control. Systematic optimization of the reaction conditions allowed good control over the polymerization, leading to the formation of polymers with well-defined architectures, exemplified by the radical block copolymerization of macrocyclic allylic sulfides and vinyl monomers and the incorporation of sequence-defined segments into the polymer backbone. This work represents a significant step toward directly enabling the polymerizations of heteroatom-centered radical propagation to be regulated by existing reversible-deactivation radical polymerization techniques.     

Distinguishing the 5,5-dimethyl-1-pyrroline N-oxide (DMPO)-OH radical quenching effect from the hydroxyl radical scavenging effect in the ESR spin-trapping method

The spin-trapping method has been widely accepted to measure the hydroxyl radical scavenging activity in electron spin resonance (ESR) spectroscopy, however, the disappearance of the trapped signal of the 5,5-dimethyl-1-pyrroline N-oxide (DMPO)-OH radical may lead to an erroneous conclusion, as the decreased signal must result from the rapid quenching of the DMPO-OH formed. The DMPO-OH quenching activity of a compound can be measured by tracing the signal decay resulting from its addition after the cessation of DMPO-OH formation. It was found that Fe(II) ions could quench the DMPO-OH radical quite rapidly, and phosphate ions could enhance the DMPO-OH radical quenching activity of the Fe(II) ions.     

Ferromagnetic behavior of formyl-group-carrying stable thioaminyl radicals

Four formyl-group-carrying thioaminyl radicals were generated, and one radical could be isolated as radical crystals. Magnetic susceptibility measurements of the isolated radical showed a ferromagnetic regular linear-chain interaction of 2J/k(B) = 3.2 K, which was explained in terms of the X-ray crystallographic results.     

ESR方法检测竹红菌素的半醌负离子自由基

从顺磁共振波谱检测到通过竹红菌素的光诱导还原和基态竹红菌素跟脂肪胺的电子转移两条途径所得到的自由基信号, 并由电化学还原得到同一自由基, 确认它为半醌负离子自由基。竹红菌素溶液中加入芳香胺观察不到ESR信号。它的3,10位上与醌基相邻近的羟基离解以后, 无论在基态还是在激发态都观察不到ESR信号。此外, 还从吸收光谱观察到半醌负离子自由基吸收以及竹红菌素跟脂肪胺之间的相互作用。     

Photoinduced Radical Borylation of Alkyl Bromides Catalyzed by 4-Phenylpyridine

Utilizing pyridine catalysis, we developed a visible-light-induced transition-metal-free radical borylation reaction of unactivated alkyl bromides that features a broad substrate scope and mild reaction conditions. Mechanistic studies revealed a novel nucleophilic substitution/photoinduced radical formation pathway, which could be utilized to trigger a variety of radical processes.     

Cyclic Acetal-Photosensitized Polymerization. VI. Photopolymerization of 2-Vinyl-1,3-dioxolane

The photopolymerization of 2-vinyl-l,3-dioxolane (VDO) was carried out in benzene at 40° C without use of the usual radical initiator. VDO was decomposed by means of photoirradiation to a cyclic acetal radical which transformed instantly into the ester radical by β-scission of dioxolane ring: the vinyl polymerization could be initiated by the ester radical. Because of the degradative chain transfer by allylidene group, the rate of polymerization and the molecular weight of polymer were very small.     

Diffuse-reflectance laser flash photolysis of 16-(1-pyrene)-hexadecanoic acid adsorbed on silica

The absorption and fluorescence of 16-(1-pyrene)-hexadecanoicacid adsorbed on silica have been investigated. Time-resolved transient diffuse reflectance spectra were recorded following pulsed nanosecond laser excitation at 355 nm of pyrene, 1-methylpyrene and 16-(1-pyrene)-hexadecanoicacid adsorbed on silica. In addition to a rapidly decaying transient, absorbing at 420 nm assigned as the triplet state, and of the radical cation, absorbing at 460 nm, another long living transient species absorbing at 420 nm was observed for 16-(1-pyrene)-hexadecanoic acid. The decay is reversible but complete recovery takes several hours. Although no definitive assignment could be made for this transient several possibilities are discussed. The radical cations of the investigated molecules are formed by a biphotonic process. The non-exponential decay of the radical cations could be analyzed in the framework of a Gaussian distribution of free energy barriers.     

Straightforward asymmetric entry to highly functionalized medium-sized rings fused to beta-lactams via chemo- and stereocontrolled divergent radical cyclization of Baylis-Hillman adducts derived from 4-oxoazetidine-2-carbaldehydes

DABCO promoted reactions of various activated vinyl systems with optically pure 4-oxoazetidine-2-carbaldehydes 1 gave rise to Baylis-Hillman adducts 3 with excellent syn stereoselectivities, without detectable racemization. Products 3 are used for the asymmetric preparation of unusual 2-azetidinones fused to medium-sized rings via chemo- and stereocontrolled divergent radical cyclization. The formation of bicyclic beta-lactams 4-6 could be rationalized through a tandem radical Michael addition/endo cyclization or a tandem radical addition/Michael addition, depending on the electronic nature of the radical promoter.     

Studies on fluoroalkylation and fluoroalkoxylation. Part 24. Magnesium-induced single electrons transfer in reactions of fluoroalkyl iodides with alkenes and alkynes

Magnesium metal catalyses the radical reactions of perfluoroakyl iodides with alkenes and alkynes to give the corresponding adducts in high yields under mild conditions. The presence of 1,4-dinitrobenzene (p-DNB) or oxygen does not affect the reaction, but the reactions can be partially suppressed by hydroquinone and completely inhibited by 2-nitroso. 2-nitropropane in DMF. In THF fluoroalkene is obtained in addition to the normal adducts, and the reaction could be inhibited by p-DNB. All these results seem to show that a radical mechanism is involved in non-ethereal solvents. However, both radical addition and fluroalkyl Grignard reagent reactions are involved in THF. The formation of fluoroalkylmagnesium iodide is also found to proceed through a radical intermediate.     

Hydroindation of allenes and its application to radical cyclization

Hydroindation of allenes and radical cyclization of 1,2,7-trienes (allenenes) were accomplished by HInCl2 with high regioselectivity to afford a variety of cyclic compounds. The resulting vinylic indiums could be used for successive coupling reactions in a one-pot procedure. The use of HInCl2 generated slowly in situ is extremely effective for the radical cyclization.     

Amidyl Radical Directed Remote Allylation of Unactivated sp3 C−H Bonds by Organic Photoredox Catalysis

The development of visible‐light‐mediated allylation of unactivated sp³ C?H bonds is reported. The remote allylation was directed by the amidyl radical, which was generated by photocatalytic fragmentation of a pre‐functionalized amide precursor. Both aromatic and aliphatic amide derivatives could successfully deliver the remote C?H allylation products in good yields. A variety of electron deficient allyl sulfone systems could be used as δ‐carbon radical acceptor.     

Photoinduced Radical Borylation of Alkyl Bromides Catalyzed by 4‐Phenylpyridine

Utilizing pyridine catalysis, we developed a visible‐light‐induced transition‐metal‐free radical borylation reaction of unactivated alkyl bromides that features a broad substrate scope and mild reaction conditions. Mechanistic studies revealed a novel nucleophilic substitution/photoinduced radical formation pathway, which could be utilized to trigger a variety of radical processes.