Mutual Deactivation Research Articles

One-pot chemo- and photo-enzymatic linear cascade processes.

The combination of chemo- and photocatalyses with biocatalysis, which couples the flexible reactivity of the photo- and chemocatalysts with the highly selective and environmentally friendly nature of enzymes in one-pot linear cascades, represents a powerful tool in organic synthesis. However, the combination of photo-, chemo- and biocatalysts in one-pot is challenging because the optimal operating conditions of the involved catalyst types may be rather different, and the different stabilities of catalysts and their mutual deactivation are additional problems often encountered in one-pot cascade processes. This review explores a large number of transformations and approaches adopted for combining enzymes and chemo- and photocatalytic processes in a successful way to achieve valuable chemicals and valorisation of biomass. Moreover, the strategies for solving incompatibility issues in chemo-enzymatic reactions are analysed, introducing recent examples of the application of non-conventional solvents, enzyme-metal hybrid catalysts, and spatial compartmentalization strategies to implement chemo-enzymatic cascade processes.

Recent advances in co-immobilization of organic acids and bases for cooperative and tandem catalysis

Acid–base bifunctional catalysts have been extensively used for a series of CC bond formation reactions. Among these catalysts, organic acid–base catalysts have attracted wide attention due to their structural variety, conformational dynamics, and enantioselectivity. To prevent mutual deactivation, a simple, effective, and versatile strategy is the attachment of both acid and base onto the surfaces of supports. In particular, the co-immobilization of organic acids and bases not only enhances synergistic effects in cooperative catalysis but also improves yields to desired products by controlling the diffusion of intermediates in tandem catalysis, leading to significant improvements in energy and atom efficiency. In this review, we highlight recent works addressing the broad topic of the co-immobilization of organic acids and bases for cooperative and tandem catalysis. We mainly focus on the synthetic strategies for silica-supported organic acid–base catalysts and polymer-supported organic acid–base catalysts. Furthermore, we summarize and discuss the structure–activity relationships of these catalysts. Last, the remaining issues and prospects will be discussed to advance the rational design and engineering of co-immobilized acid–base bifunctional catalysts.

Design and Preparation of a Bifunctional Nanobiohybrid Catalyst by Combining Palladium and α‐Amylase Enzyme: Application in One‐pot Chemoenzymatic Catalysis

AbstractA chemoenzymatic approach that combines chemical and bio‐catalyst has proven very useful in synthetic chemistry, however, mutual deactivation of chemical and bio‐catalyst when employed in the same pot is still a challenge. In this context, the development of nanobiohybrid catalysts has played an important role and overcoming the issue of mutual deactivation between catalysts to a certain extent. Herein, we design and synthesize a novel heterogeneous recyclable nanobiohybrid catalyst comprising palladium nanoparticles and α‐amylase from Aspergillus oryzae immobilized onto halloysite nanotubes as a solid heterogeneous support. Further, the wider applicability of the developed nanobiohybrid catalyst is revealed in the one‐pot chemoenzymatic synthesis of functionalized biphenyls and bis(indolyl)methanes which consists of Pd‐catalyzed Suzuki‐Miyaura coupling and α‐amylase mediated aza‐Michael addition or electrophilic substitution reactions respectively. Further, the robustness and generality of the developed one‐pot chemoenzymatic synthesis are demonstrated by incorporating different substitutions at the starting materials and obtaining the corresponding products in moderate to good yields.

A Chemoenzymatic Cascade Combining a Hydration Catalyst with an Amine Dehydrogenase: Synthesis of Chiral Amines

The combination of biocatalysis and transition-metal catalysis can complement synthetic gaps only in a chemical or biological process. However, the intrinsic mutual deactivation between enzymatic and chemical species is a significant challenge in a single operation. To address the above issue, we developed an encapsulated Au/carbene combined with a free amine dehydrogenase as a co-catalyst system that enables an efficient hydration/amination enantioselective cascade process to be accomplished. The mechanistic investigation discloses dual catalysis comprised of alkyne hydration, followed by a reductive amination process.

A Chemoenzymatic Cascade Combining a Hydration Catalyst with an Amine Dehydrogenase: Synthesis of Chiral Amines

AbstractThe combination of biocatalysis and transition‐metal catalysis can complement synthetic gaps only in a chemical or biological process. However, the intrinsic mutual deactivation between enzymatic and chemical species is a significant challenge in a single operation. To address the above issue, we developed an encapsulated Au/carbene combined with a free amine dehydrogenase as a co‐catalyst system that enables an efficient hydration/amination enantioselective cascade process to be accomplished. The mechanistic investigation discloses dual catalysis comprised of alkyne hydration, followed by a reductive amination process.

Phase Separation‐Promoted Redox Deracemization of Secondary Alcohols over a Supported Dual Catalysts System

AbstractUnification of oxidation and reduction in a one‐pot deracemization process has great significance in the preparation of enantioenriched organic molecules. However, the intrinsic mutual deactivation of oxidative and reductive catalysts and the extrinsic incompatible reaction conditions are unavoidable challenges in a single operation. To address these two issues, we develop a supported dual catalysts system to overcome these conflicts from incompatibility to compatibility, resulting in an efficient one‐pot redox deracemization of secondary alcohols. During this transformation, the TEMPO species onto the outer surface of silica nanoparticles catalyze the oxidation of racemic alcohols to ketones, and the chiral Rh/diamine species in the nanochannels of the thermoresponsive polymer‐coated hollow‐shell mesoporous silica enable the asymmetric transfer hydrogenation (ATH) of ketones to chiral alcohols. To demonstrate the general feasibility, a series of orthogonal oxidation/ATH cascade reactions are compared to prove the compatible benefits in the elimination of their deactivations and the balance of the cascade directionality. As presented in this study, this redox deracemization process provides various chiral alcohols with enhanced yields and enantioselectivities relative to those from unsupported dual catalysts systems. Furthermore, the dual catalysts can be recycled continuously, making them an attractive feature in the application.

Bifunctional Metal-Organic Layer with Organic Dyes and Iron Centers for Synergistic Photoredox Catalysis.

Here we report the design of a bifunctional metal-organic layer (MOL), Hf-EY-Fe, by bridging eosin Y (EY)-capped Hf6 secondary building units (SBUs) with Fe-TPY (TPY = 4'-(4-carboxyphenyl)[2,2':6',2''-terpyridine]-5,5''-dicarboxylate) ligands. With the organic dye EY as an efficient photosensitizer and TPY-Fe(OTf)2 as the catalytic center, Hf-EY-Fe efficiently catalyzes aminotrifluoromethylation, hydroxytrifluoromethylation, and chlorotrifluoromethylation of alkenes. Hf-EY-Fe also catalyzes the synthesis of CF3-substituted derivatives of large bioactive molecules such as rotenone, estrone, and adapalene with sizes of up to 2.2 nm. The proximity between EY and iron centers and their site isolation in Hf-EY-Fe enhance catalytic activity while inhibiting their mutual deactivation, leading to high turnover numbers of up to 1840 and good recyclability of the MOL catalyst.

Atypical Inter-Network Deactivation Associated With the Posterior Default-Mode Network in Autism Spectrum Disorder.

Previous studies have suggested that atypical deactivation of functional brain networks contributes to the complex cognitive and behavioral profile associated with autism spectrum disorder (ASD). However, these studies have not considered the temporal dynamics of deactivation mechanisms between the networks. In this study, we examined (a) mutual deactivation and (b) mutual activation-deactivation (i.e., anticorrelated) time-lag patterns between resting-state networks (RSNs) in young adults with ASD (n = 20) and controls (n = 20) by applying the recently defined dynamic lag analysis (DLA) method, which measures time-lag variations peak-by-peak between the networks. In order to achieve temporally accurate lag patterns, the brain imaging data was acquired with a fast functional magnetic resonance imaging (fMRI) sequence (TR = 100 ms). Group-level independent component analysis was used to identify 16 RSNs for the DLA. We found altered mutual deactivation timings in ASD in (a) three of the deactivated and (b) two of the transiently anticorrelated (activated-deactivated) RSN pairs, which survived the strict threshold for significance of surrogate data. Of the significant RSN pairs, 80% included the posterior default-mode network (DMN). We propose that temporally altered deactivation mechanisms, including timings and directionality, between the posterior DMN and RSNs mediating processing of socially relevant information may contribute to the ASD phenotype. LAY SUMMARY: To understand autistic traits on a neural level, we examined temporal fluctuations in information flow between brain regions in young adults with autism spectrum disorder (ASD) and controls. We used a fast neuroimaging procedure to investigate deactivation mechanisms between brain regions. We found that timings and directionality of communication between certain brain regions were temporally altered in ASD, suggesting atypical deactivation mechanisms associated with the posterior default-mode network.

One‐Pot Two‐Step Chemoenzymatic Cascade for the Synthesis of a Bis‐benzofuran Derivative

Chemoenzymatic cascades enable reactions with the high productivity of chemocatalysts and high selectivity of enzymes. Nevertheless, the combination of these different fields of catalysis is prone to mutual deactivation of metal‐ and biocatalysts. In this study, a one‐pot sequential two‐step catalytic cascade reaction was successfully implemented for the synthesis of a methylene‐bridged bis(2‐substituted benzofuran). In the first step, a palladium‐free Sonogashira reaction is used for the synthesis of a benzofuran derivative. In the subsequent step, the formed 2‐substituted benzofuran is hydroxylated by the monooxygenase P450 BM3 variant (A74S‐F87V‐L188Q) and undergoes further elimination reactions. The study proofs that combination of Cu scorpionate catalyzed Sonogashira cross‐coupling and P450 mediated oxidation is possible and results in up to 84 % yield of the final product. The oxidation reaction is boosted by capturing inhibiting reaction components.

Cooperative N-Heterocyclic Carbene/Palladium-Catalyzed Enantioselective Umpolung Annulations

A combination of NHC organocatalysis and transition-metal catalysis gives rise to fundamentally new cooperative reactivity and enables the regio- and enantioselective annulation reaction between enals and vinyl benzoxazinanones. The cooperative umpolung annulation eliminates mutual deactivation and leads to a diverse set of benzazepine derivatives in good yields with excellent enantioselectivities (up to 99% ee). The development of such a cooperative catalytic system dramatically expands the scope of NHC organocatalysis by opening up new metal-catalyzed reaction pathways for homoenolate intermediates.

Pincer ligands as powerful tools for catalysis in organic synthesis

Present trends in homogeneous catalysis are moving toward the development of multi-step, one-pot processes where salt waste is reduced to a minimum and in the lowest possible volumes of solvent. Energy efficiency is also maximized to produce the most cost-effective end product(s). However, these one pot cascade, tandem, or domino catalyzed reaction sequences rely on catalyst, substrate and solvent compatibility, on catalyst stability and on the possibility to protect these catalysts from mutual deactivation. This can be facilitated, for example, by binding these to suitable (in)soluble supports or by using compatible, stable catalysts that can be used to mediate a variety of different reactions.Pincer organometallics are powerful tools that can be used to achieve many of these objectives. The synthesis and properties of a variety of “molecularly enlarged” pincer organometallics displaying both surprising stability and versatile catalytic properties are discussed. A fascinating, recent development is the site-selective inhibition of a lipase, i.e., Cutinase, with a single pincer-metal catalytic site (see X-ray). Similarly, partial inhibition of lipases immobilized on beads with a Ru-based racemization catalyst yields a bio-organometallic hybrid catalyst, which in combination with still uninhibited lipase on these beads, can operate as a heterogeneous bifunctional catalytic material for the kinetic resolution of racemic alcohols to afford enantiopure product(s).

Cooperative Bimetallic Redox Reactivity

Binucleating ligands possessing contiguous 6-coordinate and 4-coordinate sites are described, and the redox properties of their bimetallic complexes have been investigated. The design of the two parts of these ligands is based on the redox and reactivity patterns of the corresponding monometallic complexes. If the two sites were to behave as they do in the corresponding monometallic complexes, these bimetallic complexes would be expected to bind a substrate, such as dioxygen, and to reduce it by two electrons, one from each metal, as occurs in the respiratory protein, hemerythrin. This was found not to be the case. In these bimetallic complexes, oxidation of one metal leads to the deactivation of the other metal to oxidation. The origins of this mutual deactivation appear to be connected with ligand reorganization, through-bond electronic coupling, and electrostatic interactions between neighboring metals. It is suggested that, in the systems described, ligand reorganization is the dominant deactivating e...

Radiolytic Control of the Size of Colloidal Gold Nanoparticles

Solutions containing KAu(CN)2 (∼5 × 10-4 M), methanol (0.3 M), and nitrous oxide (2.5 × 10-2 M) are γ-irradiated in the presence of colloidal gold (∼6 × 10-5 M; mean particle size, 15 nm). The hydroxymethyl radicals, •CH2OH, which are generated in these solutions, reduce Au(I) in Au(CN)2-, and the reduced gold is completely deposited on the gold seeds to yield larger particles. The particle growth is followed spectrophotometrically and by electron microscopy. A mechanism is proposed in which the radicals transfer electrons to the gold particles and Au(CN)2- is subsequently reduced by the stored electrons directly at the surface of the particles. In further steps of particle enlargement, Au(CN)2- is reduced in solutions in which the gold particles synthesized in the preceding step serve as seeds, the result being larger and larger gold particles up to 120 nm. The reduction yield is discussed with respect to side reactions of the radicals, such as mutual deactivation and gold-catalyzed H2 formation. The rad...

Cooperative bimetallic reactivity

A number of bimetallic complexes of a macrocyclic binucleating ligand containing both six- and four-coordinate binding sites have been prepared in order to try to reproduce the behavior of certain metalloproteins. It was found that two-metal oxidation is severely impeded in bimetallic systems. It is postulated that the mutual deactivation of metal oxidation is principally the result of unfavorable ligand conformational adjustments which occur after the first metal is oxidized. It is shown that when these conformational restraints are removed, two-metal oxidations are possible.

Photopolymerization of acrylonitrile sensitized with a combination of aromatic ketone and amine

AbstractEffect of amines on photopolymerization of acrylonitrile sensitized with various sensitizers was investigated in N, N‐dimethylformamide at 30°C. Photopolymerizations sensitized with aromatic ketones such as benzophenone (BP), fluorenone (Fl), acetophenone, and Michler's ketone were noticed to be activated by triethylamine (TEA). Diethylamine, tri‐n‐butylamine, di‐n‐butylamine, and n‐butylamine besides TEA also proved to be effective for the system sensitized with BP or Fl. On the other hand, TEA indicated a negative effect for systems sensitized with α,α′‐azobisisobutylonitrile (AIBN), benzoyl peroxide (BPO), benzoin, and 2‐tert‐butylanthraquinone. Characteristics of the BP—and Fl—amine‐sensitized systems were compared with the systems sensitized with AIBN, BPO, and benzoin with respect to kinetics. Contrary to the latter polymerizations following the general kinetics, including the termination of growing chains by mutual deactivation, the former polymerizations were characterized by an elevated susceptibility of the primary radical termination.

Laser flash photolysis investigation of primary processes in the sensitized polymerization of vinyl monomers IV: experiments with hydroxy alkylphenones

1-phenyl-2-hydroxy-2-methyl-propanone-1 (compound I) and 1-[4-(2-propyl)-phenyl]-2-hydroxy-2-methyl-propanone-1 (compound II) were irradiated at room temperature with 25 ns laser flashes (λ = 347 nm) and with 15 ns flashes (λ = 265 nm) in deaerated solutions of various solvents. Triplet excited ketone molecules were formed (φ(T) ≈ 0.25) which decomposed essentially by α cleavage in the absence of an effective hydrogen donor. The triplet lifetimes were found to be 30 – 50 ns. In the absence of unsaturated compounds or oxygen the radicals formed during or immediately after the flash decayed predominantly by mutual deactivation. Two modes of radical absorption decay were detected with first half-lifetimes of about 4 μs and 0.8 ms. In the presence of oxygen a strongly absorbing species was formed after the flash, due to the reaction of O 2 with fragment radicals of the ketones. The results can be used to explain why compounds I and II are capable of acting very effectively as polymerization initiators in many cases.

Free Tenside Radicals and Micellar Equilibria

Three tensides (1-(6-dodecylbenzene-sulfonate)-Na; myristyltriethyleneglycol-ether-sulfonate-Na; cetyl-21-ethyleneglycol-ether) were σ− and electron irradiated in aqueous solution. The OH radicals produced in the radiolysis of water attacked the tensides to form organic radicals either by hydrogen abstraction or addition to the aromatic ring. The decay of the organic radicals was followed optically and the rate constant for bimolecular deactivation measured at different tenside concentrations. In these case of the two anionic micelles, mutual deactivation of radicals in micelles is not possible because of the Coulombic repulsion between the micelles. Deactivation can occur after the exit of a radical from its micelle. The kinetics of radical-radical deactivation is therefore strongly ruled by the dynamics of the micellar equilibrium Mn → Mn+1 K M. All rate constants of this equilibrium can be obtained from the analysis of the kinetic data. In the case of the neutral micelles, radicals in micelles do activate each other. In these micelles, more than one radical could be produced. Intramicellar radical-radical deactivation was observed in the microsecond range, intermicellar deactivation in the millisecond range. σ-irradiation led to crosslinking of the tenside molecules.

Free Tenside Radicals and Micellar Equilibria

AbstractThree tensides (1‐(6‐dodecylbenzene‐sulfonate)‐Na; myristyltriethyleneglycol‐ether‐sulfonate‐Na; cetyl‐21‐ethyleneglycol‐ether) were σ− and electron irradiated in aqueous solution. The OH radicals produced in the radiolysis of water attacked the tensides to form organic radicals either by hydrogen abstraction or addition to the aromatic ring. The decay of the organic radicals was followed optically and the rate constant for bimolecular deactivation measured at different tenside concentrations.In these case of the two anionic micelles, mutual deactivation of radicals in micelles is not possible because of the Coulombic repulsion between the micelles. Deactivation can occur after the exit of a radical from its micelle. The kinetics of radical‐radical deactivation is therefore strongly ruled by the dynamics of the micellar equilibrium Mn → Mn+1 K M. All rate constants of this equilibrium can be obtained from the analysis of the kinetic data.In the case of the neutral micelles, radicals in micelles do activate each other. In these micelles, more than one radical could be produced. Intramicellar radical‐radical deactivation was observed in the microsecond range, intermicellar deactivation in the millisecond range. σ‐irradiation led to crosslinking of the tenside molecules.

Primary ionic species of 1,1-diphenylethylene produced by high energy radiation

1,1-Diphenylethylene (DPE) has been irradiated with 20 ns pulses of 15 MeV electrons at room temperature in dichloromethane solution and at 77 K in a 1:1- n-buty-chloride-isopentane matrix with 60Co-γ-rays. A comparison of the results led to the following conclusions. Associated dimer radical cations (M) 2 ± (absorbing at 395 nm and between 1000 nm and 1200 nm) are generated within the pulse. They form an equilibrium (M) 2 ± ▪M ±+M ( k e=(2.0±0.4)x10 6s -1). The decay of the radical cations follows first order kinetics ( k 0=(1.1±0.3)x10 5 s -1) probably due to a reaction with traces of an impurity. Thereby free radicals are formed, absorbing between 300 nm and 350 nm (peak at 335 nm). The radicals decay according to a second order process ((2 k/ϵ)= (3.2±0.3)x10 3 cm s -1) by mutual deactivation. Ethanol causes a diminution of the initial spectrum, since it competes with DPE for solvent radical cations S ±. Ethanol reacts with M ± with k EtOH+M ± =1x 10 8 M -1 s -1.

O - transfer reactions of the carbonate radical anion

The CO 3 - radical is produced in the pulse radiolysis of N 2O containing carbonate solutions (1–6) (1) OH + CO 3 2- → OH - + CO 3 -. Although it is known that it disappears via mutual deactivation with 2 k = 1.5 × 10 7 M -1 S -1, the products of this deactivation have not yet been unambiguously recognized. In the previous pulse radiolysis work, only optical absorption measurements were carried out to trace the short-lived intermediates. In the present work, the conductivity changes that often accompany the changes in optical absorption of irradiated solutions, were recorded also. The a.c. method used and the evaluation of the data have been described earlier. (7,8)It is shown that CO 3 - radicals react with each other and with other radicals such as NO 2 and SO 3 - via the transfer of an O - ion. The resulting CO 2 was detected by the conductivity changes that accompany its reaction with water. Reaction of CO 3 - with CH 3 proceeds through a long-lived complex.