Amine Donor Research Articles

Alkyl initiated ring opening polymerization of lactide by indium complexes supported by NCN pincer ligands.

Indium-alkyl NCN pincer complexes supported by amine and imine donors are active catalysts for the ring opening polymerization of lactide. The amine indium complexes are significantly more active for polymerization due to the decoordination of the amine donors at higher temperatures. Solid state structures of the imine and amine indium complexes indicate that the imine-indium bonds are stronger than the analogous amine-indium bonds. Higher molecular weight polymers that were not observable by MALDI-TOF were shown to be linear by comparing their intrinsic viscocities with those of known linear polymers. The alkyl indium complexes are more active than the analogous alkyl aluminum complexes but are prone to transesterification reactions.

Tracking Small Extracellular Vesicles Using a Minimally Invasive PicoGreen Labeling Strategy.

Extracellular vesicles (EVs) are cell-secreted lipid bilayer delimited particles that mediate cellular communication. These tiny sacs of cellular information play an important role in cell communication and alter the physiological process under both normal and pathological conditions. As such, tracking EVs can provide valuable information regarding the basic understanding of cell communication, the onset of early malignancy, and biomarker discovery. Most of the current EV-tracking strategies are invasive, altering the natural characteristics of EVs by modifying the lipid bilayer with lipophilic dyes or surface proteins with fluorescent reporters. The invasive labeling strategies could alter the natural processes of EVs and thereby have major limitations for functional studies. Here, we report an alternative minimally invasive EV labeling strategy using PicoGreen (PG), a small molecule that fluoresces at 520 nm when bound to dsDNA. We show that PG binds to dsDNA associated with small EVs (50-200 nm), forming a stable and highly fluorescent PG-DNA complex in EVs (PG-EVs). In both 2D cell culture and 3D organoid models, PG-EV showed efficient tracking properties, including a high signal-to-noise ratio, time- and concentration-dependent uptake, and the ability to traverse a 3D environment. We further validated PG-EV tracking using dual-labeled EVs following two orthogonal labeling strategies: (1) Bioconjugation via surface amine labeling and (2) donor cell engineering via endogenously expressing mCherry-tetraspanin (CD9/CD63/CD81) reporter proteins. Our study has shown the feasibility of using PG-EV as an effective EV tracking strategy that can be applied for studying the functional role of EVs across multiple model systems.

Elevating biotransamiantion of pineapple peel-derived furfural into furfurylamine by recombinant Escherichia coli carrying pyruvate decarboxylase and mutant ω-transaminase with low loading of amine donor

Furfurylamine is a versatile compound used in perfumes, polymers, pharmaceuticals, and agrochemicals. To address the costly and inefficient furfural bioamination process, a strategy combining ω-transaminase with other enzymes was applied to construct a multi-enzyme system. Pyruvate decarboxylase (PDC) might transform amination byproducts into acetaldehyde, promoting the forward bioreaction. E. coli 20PDC was created by co-expressing PDC and mutated ω-transaminase (HN), which could be applied to efficiently aminate furfural, vanillin and 5-hydroxymethylfurfural into furfuryalmine, vanillylamine, and 5-hydroxymethyl-2-furfurylamine, respectively. Pineapple peel can be used as a suitable feedstock for production of furfural and furfurylamine. A chemobiological cascade reaction was built to transform pineapple peel into furan-based amines in deep eutectic solvent ChCl:pA-H2O. In ChCl:pA (10 wt%) at 170 °C, pineapple peel was converted to furfural within 10 min (65.2% yield, based on xylan), and the pineapple peel-derived furfural was resoundingly converted to furfurylamine at 35 °C with D-alanine (D-alanine:substrate = 2:1) in ChCl:pA (20 wt%, pH 7.5). This dual-enzyme co-expression strategy reduced the amine donor loading and realized the effectual bioamination from biomass-derived aldehydes. To sum up, the strategy for synthesis of FAM from pineapple peel by tandem chemocatalysis and biocatalysis in ChCl:pA-H2O holds significant promising in the valorization of biomass into valuable furans.

Biocatalytic Desymmetrization for the Atroposelective Synthesis of Axially Chiral Biaryls Using an Engineered Imine Reductase.

The enzymatic atroposelective synthesis of biaryl compounds is relatively rare, despite considerable attention received by biocatalysis in academic and industrial sectors. Imine reductases (IREDs) are an important class of enzymes that have been applied in the asymmetric synthesis of chiral amine building blocks. In this work, two IREDs (IR140 and IR189) were identified to catalyze the efficient desymmetrization of biaryls utilizing various amine donors. Further protein engineering enabled the identification of variants (IR189 M8-M9 and IR189 M13-M14) that are able to catalyze the formation of both (R) and (S) atropisomers in excellent yields and atroposelectivities for up to 24 examples (up to 99% ee and yield). The absolute configuration and rotational barriers were confirmed, and the reactions were readily enlarged to allow isolation of the atropisomeric products in 99% ee and 82% isolated yields. The optically pure biaryl amines were further derivatized into various synthetically useful atropisomers. To shed light on the molecular recognition mechanisms, molecular dynamics (MD) simulations were performed, offering plausible explanations for the improved atroposelectivities and enzymatic activities. The current strategy expands the scope of IRED-catalyzed synthesis of axially chiral biaryl amines, contributing significantly to the field of atroposelective biocatalysis.

Current Status of Amine Dehydrogenases: From Active Site Architecture to Diverse Applications Across a Broad Substrate Spectrum

AbstractAmine dehydrogenases (AmDHs) are NAD(P)H‐dependent oxidoreductases that catalyze the reductive amination between carbonyl compounds and ammonia as the amine donor yielding valuable amines, typically with excellent enantioselectivity. While nature has provided enzymes with inherent AmDH activities, protein engineering techniques allowed researchers to expand the toolbox of available AmDHs, extend their substrate scope, improve their catalytic activities and stability under synthetically relevant conditions and even enable new reactivity concepts. The biocatalytic synthesis of amines using AmDHs has matured to a point where hundreds of aldehydes or ketones, of varying steric demands and bearing diverse functional groups, can be efficiently transformed. This review offers an overview of the available AmDHs and their substrate spectrum, covering from structural and evolutionary analyses to diverse methods employing these enzymes. Depending on the catalytic activities of other enzymes as reaction partners, AmDHs were applied in kinetic resolution (KR) and deracemization processes, cascade reactions for the amination of alcohols and alkenes or for the synthesis of amines and amino alcohols featuring multiple stereogenic centers. Moreover, the synthetic potential of AmDHs in novel pathways, such as the synthesis of secondary amines or alcohols, presents exciting opportunities for expanding their catalytic repertoire.

Lysine as a ‘Smart’ Amine Donor for Transaminase-Catalyzed Synthesis of β-Branched Amino Acids

Lysine as a ‘Smart’ Amine Donor for Transaminase-Catalyzed Synthesis of β-Branched Amino Acids

Efficient and rapid digestion of proteins with a dual-enzyme microreactor featuring 3-D pores formed by dopamine/polyethyleneimine/acrylamide-coated KIT-6 molecular sieve

The microreactor with two types of immobilized enzymes, exhibiting excellent orthogonal performance, represents an effective approach to counteract the reduced digestion efficiency resulting from the absence of a single enzyme cleavage site, thereby impacting protein identification. In this study, we developed a hydrophilic dual-enzyme microreactor characterized by rapid mass transfer and superior enzymatic activity. Initially, we selected KIT-6 molecular sieve as the carrier for the dual-IMER due to its three-dimensional network pore structure. Modification involved co-deposition of polyethyleneimine (PEI) and acrylamide (AM) as amine donors, along with dopamine to enhance material hydrophilicity. Remaining amino and double bond functional groups facilitated stepwise immobilization of trypsin and Glu-C. Digestion times for bovine serum albumin (BSA) and bovine hemoglobin (BHb) on the dual-IMER were significantly reduced compared to solution-based digestion (1 min vs. 36 h), resulting in improved sequence coverage (91.30% vs. 82.7% for BSA; 90.24% vs. 89.20% for BHb). Additionally, the dual-IMER demonstrated excellent durability, retaining 96.08% relative activity after 29 reuse cycles. Enhanced protein digestion efficiency can be attributed to several factors: (1) KIT-6’s large specific surface area, enabling higher enzyme loading capacity; (2) Its three-dimensional network pore structure, facilitating faster mass transfer and substance diffusion; (3) Orthogonality of trypsin and Glu-C enzyme cleavage sites; (4) The spatial effect introduced by the chain structure of PEI and glutaraldehyde’s spacing arm, reducing spatial hindrance and enhancing enzyme–substrate interactions; (5) Mild and stable enzyme immobilization. The KIT-6-based dual-IMER offers a promising technical tool for protein digestion, while the PDA/PEI/AM-KIT-6 platform holds potential for immobilizing other proteins or active substances.

A refined picture of the native amine dehydrogenase family revealed by extensive biodiversity screening

Native amine dehydrogenases offer sustainable access to chiral amines, so the search for scaffolds capable of converting more diverse carbonyl compounds is required to reach the full potential of this alternative to conventional synthetic reductive aminations. Here we report a multidisciplinary strategy combining bioinformatics, chemoinformatics and biocatalysis to extensively screen billions of sequences in silico and to efficiently find native amine dehydrogenases features using computational approaches. In this way, we achieve a comprehensive overview of the initial native amine dehydrogenase family, extending it from 2,011 to 17,959 sequences, and identify native amine dehydrogenases with non-reported substrate spectra, including hindered carbonyls and ethyl ketones, and accepting methylamine and cyclopropylamine as amine donor. We also present preliminary model-based structural information to inform the design of potential (R)-selective amine dehydrogenases, as native amine dehydrogenases are mostly (S)-selective. This integrated strategy paves the way for expanding the resource of other enzyme families and in highlighting enzymes with original features.

Biocatalytic Oxidative Amination of para‐Substituted Phenols

AbstractBiocatalytic preparation of chiral amines is a large and burgeoning field in organic chemistry. Many enzymes and routes have been published, including transaminases, imine reductases, reductive aminases, amine dehydrogenases and others. However, all these routes rely on some sacrificial substrate, in the form of either amine donor or cofactor regeneration substrate. Herein, we report the direct oxidative amination of p‐substituted phenols catalyzed by an evolved flavoprotein oxidase, with the consumption of only substrate and O2, and release of H2O2. The substrate scope of the reaction is studied, and is tolerant of a diverse panel including ammonia, primary and secondary amines, and amino acids. The reaction is later employed at preparative scale to generate aminated products in 50–80 % yield. This report establishes flavoprotein oxidase as a new and economical member of the chemist's toolkit for biocatalytic generation of chiral amines, acting as oxidative aminase.

Transaminase-Catalyzed Synthesis of β-Branched Noncanonical Amino Acids Driven by a Lysine Amine Donor.

Transaminases are choice biocatalysts for the synthesis of chiral primary amines, including amino acids bearing contiguous stereocenters. In this study, we employ lysine as a "smart" amine donor in transaminase-catalyzed dynamic kinetic resolution reactions to access β-branched noncanonical arylalanines. Our mechanistic investigation demonstrates that, upon transamination, the lysine-derived ketone byproduct readily cyclizes to a six-membered imine, driving the equilibrium in the desired direction and thus alleviating the need to load superstoichiometric quantities of the amine donor or deploy a multienzyme cascade. Lysine also shows good overall compatibility with a panel of wild-type transaminases, a promising hint of its application as a smart donor more broadly. Indeed, by this approach, we furnished a broad scope of β-branched arylalanines, including some bearing hitherto intractable cyclopropyl and isopropyl substituents, with high yields and excellent selectivities.

Divergent Protein Engineering of Transaminase for the Synthesis of Chiral Rivastigmine and Apremilast Precursors†

Comprehensive SummaryThe implementation of divergent protein engineering on the natural transaminase Vf‐ω‐TA led to the development of two effective mutants (M2 and M8), enabling the enzymatic synthesis of chiral amine precursors of Rivastigmine and Apremilast, respectively. The evolution of the enzymes was guided by crystal structures and a focused mutagenesis strategy, allowing them to effectively address the challenging ketone substrates with significant steric hindrance. Under the optimized reaction parameters, transamination proceeded smoothly in good conversions and with perfect stereochemical control (> 99% ee). These processes utilize inexpensive α‐methylbenzylamine as an amine donor and avoid the continuous acetone removal and costly LDH/GDH/NADH systems.

Electron Donor‐Acceptor (EDA) Complex Enabled C−C Cross‐Coupling Reactions of α‐Amino Radicals

AbstractElectron‐donor acceptor (EDA) complex has been an integral part of visible‐light photocatalysis and is different from the traditional photoredox catalysis, which requires an exogenous photocatalyst, typically a colored compound to initiate the photocatalytic cycle. Interestingly, the EDA‐complex photochemistry has found profound use in activating the inert α‐C−H bonds of amines. The strategy relied upon the formation of colored EDA‐complex between the donor (amine) and acceptor (Lewis acid), which upon harvesting light energy perform a SET process to generate radical cation and anion intermediates. The radical cation then loses the activated acidic proton (because of the SET, the acidity of α‐proton increases by lowering the BDE) to form α‐amino radical, which then participates in various C−C coupling cascades. In this review, different conceptual approaches for the generation of α‐amino radicals and their coupling for the C−C bond‐forming reaction under EDA‐complex triggered photocatalysis will be discussed with particular emphasis on the reaction mechanism from 2018 onwards.

Synthesis of inverse push-pull coumarin dyes and their application as solvatochromic probes and labelling agents for bacterial cell membranes

Coumarin derivatives have been widely employed across a great number of applications, such as laser dyes, bioimaging or chemossensors, owing to their strong fluorescence and high-quantum yields. These properties are highly tunable through structural modification, namely by the inclusion of electron-withdrawing groups (EWG) and electron-donating groups (EDG) at positions 3 and 7 of the coumarin scaffold, respectively. Comparatively, there aren't many reports of EDGs being employed at position 3, prompting us to investigate this new class of potential fluorophores.We undertook the synthesis of three novel ethynyl-linked aminophenyl-coumarin dyes, employing a key Sonogashira-coupling reaction to introduce the electron-rich tertiary aniline moiety. Two different amine donors were used, diphenylamino (coumarins A and B) and dimethylamino (coumarin C), as well as two alkoxy substituents, dibenzyloxy (A and C) and methylenedioxy (B), in the phenyl ring of the coumarin. All dyes show strong emission and significant positive solvatochromism. Additionally, they were employed as staining agents for the cellular membrane of S. pneumoniae, a Gram-positive bacterial pathogen. None of the three derivatives presented cytotoxic effects. Only A and B successfully labelled the bacterial membrane. In the case of B a very similar staining pattern and performance to that of standard dye Nile Red was observed, while A seemed to possess a more selective distribution.

Engineering the enantioselectivity of a novel imine reductase from Streptomyces viridochromogenes for the dynamic kinetic reductive amination of cyclic β-ketoester

N-substituted β-amino esters as an important class of chiral amines, are widely used as building blocks in pharmaceuticals. A novel imine reductase SvIRED was identified through gene mining from Streptomyces viridochromogenes with high enantioselectivity of > 99 % ee (1R, 2S), 95 % de (cis:trans), towards 2-oxocyclohexane-1-carboxylate and cyclopropylamine. SvIRED exhibited the highest activity at pH 7.0 and 40 °C. A variety of amine donors could be used by SvIRED and produce chiral N-substituted β-amino esters with different enantioselectivity. Employing methylamine (i) and pyrrolidine (n) as amine donors, SvIRED exhibited reversed enantioselectivity of 23 % ee (1S, 2R) and 79 % ee (1S, 2R) respectively. Through alanine scanning, M183 and H244 were identified with remarkable roles in governing enantioselectivity towards i and n. Compared with WT SvIRED, the enantioselectivity of M183A was inverted to ee value of >99 % (1R, 2S) and de value of >99 % (cis:trans) towards i, and the enantioselectivity of H244A was inverted to ee value of 88 % (1R, 2S) and de value of >99 % (cis:trans) towards n. Interaction analysis indicated the orientation of ester group was vital for manipulation of enantioselectivity. This study provides novel Imine reductase mutants for enantioselective synthesis of N-substituted β-amino esters with different amine donors.

One-pot Twostep Chemobiocatalytic Synthesis of a Furan Amino Acid from 5-Hydroxymethylfurfural.

Recently, catalytic valorization of biomass-derived furans has received growing interest. 5-Aminomethyl-2-furancarboxylic acid (AMFC), a furan amino acid, holds great promise in the aeras of polymer and pharmaceutical, but its synthesis remains limited. In this work, we report a chemobiocatalytic route toward AMFC by combining laccase-TEMPO system and recombinant Escherichia coli (named E. coli_TAF) harboring ω-transaminase (TA), L-alanine dehydrogenase (L-AlaDH) and formate dehydrogenase (FDH), starting from 5-hydroxymethylfurfural (HMF). In the cascade, HMF is oxidized into 5-formyl-2-furancarboxylic acid (FFCA) by laccase-TEMPO system, and then the resulting intermediate is converted into AMFC by E. coli_TAF via transamination with cheap ammonium formate instead of costly organic amine donors, theoretically generating H2O and CO2 as by-products. The tandem process was run in a one-pot twostep manner, affording AMFC with approximately 81 % yield, together with 10 % 2,5-furandicarboxylic acid (FDCA) as by-product. In addition, the scale-up production of AMFC was demonstrated, with 0.41 g/L h productivity and 8.6 g/L titer. This work may pave the way for green manufacturing of the furan-containing amino acid.

Effects of fused thiophene Π-bridge on the electronic and optical properties of modified theaflavin natural dye

ABSTRACT Natural dye sensitizers are substances that are sensitive to light colour and can be classified into several classes based on their chemical structure. Theaflavin pigments are unexplored natural dyes used as light sensitizers derived from black tea waste. However, the efficiency of natural dye-sensitized solar cells (DSSC) is lower than that of synthetic ones. To increase the efficiency, an amine donor molecule, a thiophene bridge, and a cyanoacrylic acid anchoring group were added. This improvement was achieved by comparing the LHE values, absorption shifts towards the red spectrum, and electronic parameters before and after modification of the theaflavin structure. This study aimed to analyze the effect of a fused thiophene bridge on the colour pigment of theaflavin on the electronic and optical properties of DSSC. TDDFT was employed with the hybrid functional B3LYP and def2-SVP. The calculated results concluded that adding fused thiophene can shift the wavelength with a maximum value of 256 nm and an increase in LHE of 40%. The addition of five thiophenes can shift the absorption wavelength closer to the red spectrum and satisfy the electronic properties of the DSSC, and the number of electron donor and acceptor sites obeying the law of conservation of charge.

Amino-containing donor-acceptor biaryls with lactone bridging units as three-state halochromic pi-expanded coumarins

This report describes the synthesis and study of two new amino-containing donor-acceptor lactone-bridged biaryls as pi-expanded, or benzannulated, coumarins based on the 6H-benzo[c]chromen-6-one (benzo[c]coumarin) structural unit. These fluorescent and planar compounds exhibit strong intramolecular charge transfer (ICT) through the conjugated biaryl unit via a diethylamino donor on one arene and either a nitro or cyano acceptor unit on the opposing arene. The ICT of these systems can be reversibly altered via two different stimuli: 1) addition of a strong base (hydroxide) results in nucleophilic cleavage of the lactone bridge which dramatically weakens ICT by disrupting conjugation between the individual arenes and 2) addition of a strong acid protonates the diethylamino donor unit, disrupting its ability to donate, thereby causing ICT to be attenuated. The presence of strong acid or base results in dramatic changes in optical absorption and emission properties of these systems which can be readily observed both spectroscopically and visually. Ultimately compounds containing the benzo[c]coumarin structural unit with amine donors could act as three-state halochromic molecular switches and dyes.

Study of Heterogeneity of Ethylene/1-Octene Copolymers Synthesized with Zirconium and Titanium Complexes Bearing Diamine-bis(phenolate) Ligands.

A series of ethylene/1-octene copolymers synthesized with diamine-bis(phenolate) complexes activated with Al(iBu)3/[Ph3C][B(C6F5)4] were subjected to preparative temperature rising elution fractionation (TREF). The complexes used differed in the type of metallic center (Zr or Ti) or the amine donor in the pendant arm of the ligand (NMe2 or NiPr2). The obtained fractions were then characterized via FTIR, DSC and GPC methods. It was found that all the copolymers had very broad chemical composition distributions, and the most heterogeneous was the copolymer produced by the titanium complex bearing a ligand with the NiPr2 donor group. The difference in the comonomer incorporation into the macromolecules of the fractions was as high as 8.3 mol%. The melting temperature and molecular weight of the fractions changed nearly linearly with the increased elution temperature. Copolymers produced by zirconium catalysts were also fractionated by molecular weight using the solvent/non-solvent technique with subsequent analysis of the fractions. It was shown that the fractions have a similar composition, low molecular weight distribution and very broad comonomer distribution. Therefore, the comonomer content in the fractions was not a function of the molecular weight as was observed for the copolymers synthesized with the Ziegler-Natta catalysts.

A general alkene aminoarylation enabled by N-centred radical reactivity of sulfinamides.

Arylethylamines are popular structural elements in bioactive molecules but are often made through a linear series of synthetic steps. A modular protocol to assemble arylethylamines from alkenes in one step would represent a useful advance in discovery chemistry, though current limitations preclude a generally applicable method. In this work we disclose an aminoarylation of alkenes using aryl sulfinamide reagents as bifunctional amine and arene donors. This reaction features excellent regioselectivity and diastereoselectivity on a variety of activated and unactivated substrates. Using a weakly oxidizing photocatalyst, a nitrogen radical is generated under mild conditions and adds to an alkene to form a new C-N bond. A desulfinylative aryl migration event known as a Smiles-Truce rearrangement follows to form a new C-C bond. In this manner, arylethylamines can be rapidly assembled from abundant alkene feedstocks. Moreover, chiral information from the sulfinamide can be transferred via rearrangement to a new carbon stereocentre in the product, thus advancing the development of traceless asymmetric alkene difunctionalization.

Extended Π‐Conjugation Toward Efficient Orange Purely Organic Phosphorescence OLEDs

AbstractIn purely organic room‐temperature phosphorescence (RTP) materials, fluorescence radiative transitions generally compete against inter‐system crossing (ISC) transitions to give fluorescence/phosphorescence dual emission. In order to achieve pure phosphorescence in RTP organic light‐emitting diodes (OLEDs), extended π‐conjugation is introduced into Se‐containing donors to suppress the fluorescence radiative transitions by the symmetry excited state orbitals in the introduced π–π* transitions that cancel the overlap of the orbitals, and two novel nonaromatic amine donor containing orange RTP emitters namely 2‐(benzo[c]phenoxaselenin‐10‐yl)‐4,6‐diphenyl‐1,3,5‐triazine (BPXSeDRZ) and 2‐(dibenzo[a,c]phenoxaselenin‐11‐yl)‐4,6‐diphenyl‐1,3,5‐triazine (DBPXSeDRZ) are developed, both of which exhibit efficient orange pure phosphorescence in doped films thanks to the sufficient ISC transitions. As a result, high external quantum efficiencies of 17.2% and 17.9% are respectively achieved for the orange RTP‐OLEDs based on BPXSeDRZ and DBPXSeDRZ for the first time, and they also exhibit stable pure electro‐phosphorescence spectra in a wide driving voltage. Moreover, by adopting DBPXSeDRZ as a sensitizer to harvest the triplet excitons and tetraphenyldibenzoperiflanthene as a conventional fluorescent emitter, the external quantum efficiency of the sensitized red fluorescent OLED can be elevated to 10.1%, which greatly expands the potential applications of the metal‐free phosphors in OLEDs.