ABSTRACT
To the best of our knowledge, enzymes that catalyse intramolecular Diels-Alder ([4+2] cycloaddition) reactions are frequently reported in natural product biosynthesis; however, no native enzymes utilising Lewis acid catalysis have been reported. Verticilactam is a representative member of polycyclic macrolactams, presumably produced by spontaneous cycloaddition. We report that the intramolecular [4+2] cycloadditions can be significantly accelerated by ferredoxins (Fds), a class of small iron-sulphur (Fe-S) proteins. Through iron atom substitution by Lewis acidic gallium (Ga) iron and computational calculations, we confirm that the ubiquitous Fe-S cluster efficiently functions as Lewis acid to accelerate the tandem [4+2] cycloaddition and Michael addition reactions by lowering free energy barriers. Our work highlights Nature's ingenious strategy to generate complex molecule structures using the ubiquitous Fe-S protein. Furthermore, our study sheds light on the future design of Fd as a versatile Lewis acid catalyst for [4+2] cycloaddition reactions.
Subject(s)
Biological Products , Cycloaddition Reaction , Iron-Sulfur Proteins , Lewis Acids , Biological Products/metabolism , Biological Products/chemistry , Iron-Sulfur Proteins/metabolism , Iron-Sulfur Proteins/chemistry , Lewis Acids/chemistry , Lewis Acids/metabolism , Catalysis , Iron/chemistry , Iron/metabolism , Lactams/metabolism , Lactams/chemistry , BiocatalysisABSTRACT
In enzymatic catalysis, the redox site and Lewis acid are the two main roles played by metal to assist amino acids. However, the reported enzyme mimics only focus on the redox-active metal as redox site, while the redox-inert metal as Lewis acid has, to the best of our knowledge, not been studied, presenting a bottleneck of enzyme mimics construction. Based on this, a series of highly efficient MxV2O5·nH2O peroxidase mimics with vanadium as redox site and alkaline-earth metal ion (M2+) as Lewis acid are reported. Experimental results and theoretical calculations indicate the peroxidase-mimicking activity of MxV2O5·nH2O show a periodic change with the Lewis acidity (ion potential) of M2+, revealing the mechanism of redox-inert M2+ regulating electron transfer of V-O through non-covalent polarization and thus promoting H2O2 adsorbate dissociation. The biomimetic synergetic effect of redox site and Lewis acid is expected to provide an inspiration for design of enzyme mimics.
Subject(s)
Hydrogen Peroxide , Lewis Acids , Oxidation-Reduction , Lewis Acids/chemistry , Lewis Acids/metabolism , Hydrogen Peroxide/metabolism , Hydrogen Peroxide/chemistry , Vanadium/chemistry , Vanadium/metabolism , Biomimetic Materials/chemistry , Biomimetic Materials/metabolism , Biomimetics , Peroxidase/metabolism , Peroxidase/chemistry , CatalysisABSTRACT
Nitrite and nitric oxide (NO), two active and critical nitrogen oxides linking nitrate to dinitrogen gas in the broad nitrogen biogeochemical cycle, are capable of interacting with redox-sensitive proteins. The interactions of both with heme-copper oxidases (HCOs) serve as the foundation not only for the enzymatic interconversion of nitrogen oxides but also for the inhibitory activity. From extensive studies, we now know that NO interacts with HCOs in a rapid and reversible manner, either competing with oxygen or not. During interconversion, a partially reduced heme/copper center reduces the nitrite ion, producing NO with the heme serving as the reductant and the cupric ion providing a Lewis acid interaction with nitrite. The interaction may lead to the formation of either a relatively stable nitrosyl-derivative of the enzyme reduced or a more labile nitrite-derivative of the enzyme oxidized through two different pathways, resulting in enzyme inhibition. Although nitrite and NO show similar biochemical properties, a growing body of evidence suggests that they are largely treated as distinct molecules by bacterial cells. NO seemingly interacts with all hemoproteins indiscriminately, whereas nitrite shows high specificity to HCOs. Moreover, as biologically active molecules and signal molecules, nitrite and NO directly affect the activity of different enzymes and are perceived by completely different sensing systems, respectively, through which they are linked to different biological processes. Further attempts to reconcile this apparent contradiction could open up possible avenues for the application of these nitrogen oxides in a variety of fields, the pharmaceutical industry in particular.
Subject(s)
Bacteria/enzymology , Nitric Oxide/metabolism , Nitrites/metabolism , Oxidoreductases/metabolism , Bacterial Proteins/metabolism , Gene Expression Regulation, Bacterial , Gene Expression Regulation, Enzymologic , Hemeproteins/metabolism , Lewis Acids/metabolismABSTRACT
Constructing synthetic models of the Mo/Cu active site of aerobic carbon monoxide dehydrogenase (CODH) has been a long-standing synthetic challenge thought to be crucial for understanding how atmospheric concentrations of CO and CO2 are regulated in the global carbon cycle by chemolithoautotrophic bacteria and archaea. Here we report a W/Cu complex that is among the closest synthetic mimics constructed to date, enabled by a silyl protection/deprotection strategy that provided access to a kinetically stabilized complex with mixed O2-/S2- ligation between (bdt)(O)WVI and CuI(NHC) (bdt = benzene dithiolate, NHC = N-heterocyclic carbene) sites. Differences between the inorganic core's structural and electronic features outside the protein environment relative to the native CODH cofactor point to a biochemical CO oxidation mechanism that requires a strained active site geometry, with Lewis acid/base frustration enforced by the protein secondary structure. This new mechanistic insight has the potential to inform synthetic design strategies for multimetallic energy storage catalysts.
Subject(s)
Aldehyde Oxidoreductases/metabolism , Carbon Monoxide/metabolism , Copper/metabolism , Lewis Acids/metabolism , Molybdenum/metabolism , Multienzyme Complexes/metabolism , Tungsten/metabolism , Aldehyde Oxidoreductases/chemistry , Base Pairing , Carbon Monoxide/chemistry , Copper/chemistry , Density Functional Theory , Lewis Acids/chemistry , Models, Molecular , Molecular Structure , Molybdenum/chemistry , Multienzyme Complexes/chemistry , Oxidation-Reduction , Tungsten/chemistryABSTRACT
Glycosyl phosphates are shown to be activated to stereospecific nucleophilic substitution reactions by precisely tailored bis-thiourea catalysts. Enhanced reactivity and scope is observed with phosphate relative to chloride leaving groups. Stronger binding (Km) to the H-bond donor and enhanced reactivity of the complex (kcat) enables efficient catalysis with broad functional group compatibility under mild, neutral conditions.
Subject(s)
Catalysis , Glycosylation , Phosphates/metabolism , Glycosylation/drug effects , Hydrogen Bonding , Lewis Acids/metabolism , Stereoisomerism , Thiourea/metabolismSubject(s)
Electron Spin Resonance Spectroscopy/methods , Fabaceae/chemistry , Leghemoglobin/metabolism , Nitric Oxide/analysis , Root Nodules, Plant/chemistry , Fabaceae/growth & development , Fabaceae/physiology , Fluorescein , Indicators and Reagents , Leghemoglobin/analysis , Lewis Acids/metabolism , Nitric Oxide/isolation & purification , Nitric Oxide/metabolism , Oxidation-Reduction , Root Nodules, Plant/growth & development , Root Nodules, Plant/physiology , Sensitivity and Specificity , Stress, PhysiologicalABSTRACT
The reduction of nitrate (NO3-) to nitrite (NO2-) is of significant biological and environmental importance. While MoIV(O) and MoVI(O)2 complexes that mimic the active site structure of nitrate reducing enzymes are prevalent, few of these model complexes can reduce nitrate to nitrite through oxygen atom transfer (OAT) chemistry. We present a novel strategy to induce nitrate reduction chemistry of a previously known catalyst MoIV(O)(SN)2 (2), where SN = bis(4- tert-butylphenyl)-2-pyridylmethanethiolate, that is otherwise incapable of achieving OAT with nitrate. Addition of nitrate with the Lewis acid Sc(OTf)3 (OTf = trifluoromethanesulfonate) to 2 results in an immediate and clean conversion of 2 to MoVI(O)2(SN)2 (1). The Lewis acid additive further reacts with the OAT product, nitrite, to form N2O and O2. This work highlights the ability of Sc3+ additives to expand the reactivity scope of an existing MoIV(O) complex together with which Sc3+ can convert nitrate to stable gaseous molecules.
Subject(s)
Biomimetic Materials/chemistry , Lewis Acids/chemistry , Molybdenum/chemistry , Nitrates/chemistry , Organometallic Compounds/chemistry , Oxidoreductases/chemistry , Biomimetic Materials/metabolism , Lewis Acids/metabolism , Molecular Structure , Molybdenum/metabolism , Nitrates/metabolism , Organometallic Compounds/metabolism , Oxidation-Reduction , Oxidoreductases/metabolismABSTRACT
Bent metallocenes Cp2MCl2 (M = Ti, V, Nb, Mo) are known to exhibit cytotoxic activity against a variety of cancer types. Though the mechanism of action is not fully understood yet, the accumulation of the metal ions in the nucleus points towards DNA as one of the primary targets. A set of eight deoxydinucleoside monophosphates was used to study the adduct yields with metallocenes and cisplatin. The binding affinities are reflected by the relative intensities of the adducts and were found to follow the order of Pt > V > Ti > Mo (no adducts were detected with Nb). High-resolution tandem mass spectrometry was applied to locate the binding patterns in the deoxydinucleoside monophosphates. Whereas cisplatin binds to the soft nitrogen atoms in the purine nucleobases, the metallocenes additionally interact with the hard phosphate oxygen, which is in good agreement with the hard and soft (Lewis) acids and bases (HSAB) concept. However, the binding specificities were found to be unique for each metallocene. The hard Lewis acids titanium and vanadium predominantly bind to the deprotonated phosphate oxygen, whereas molybdenum, an intermediate Lewis acid, preferentially interacts with the nucleobases. Nucleobases comprise alternative binding sites for titanium and vanadium, presumably oxygen atoms for the first and nitrogen atoms for the latter. In summary, the intrinsic binding behavior of the different metallodrugs is reflected by the gas-phase dissociation of the adducts. Consequently, MS/MS can provide insights into therapeutically relevant interactions between metallodrugs and their cellular targets. Graphical Abstract á .
Subject(s)
Antineoplastic Agents/chemistry , Dinucleoside Phosphates/chemistry , Metallocenes/chemistry , Antineoplastic Agents/metabolism , Dinucleoside Phosphates/metabolism , Lewis Acids/chemistry , Lewis Acids/metabolism , Metallocenes/metabolism , Tandem Mass SpectrometryABSTRACT
This study aimed to transform food waste into a value-added chemical, hydroxymethylfurfural (HMF), and unravel the tangled effects induced by the metal catalysts on each single step of the successive conversion pathway. The results showed that using cooked rice and bread crust as surrogates of starch-rich food waste, yields of 8.1-9.5% HMF and 44.2-64.8% glucose were achieved over SnCl4 catalyst. Protons released from metal hydrolysis and acidic by-products rendered Brønsted acidity to catalyze fructose dehydration and hydrolysis of glycosidic bond. Lewis acid site of metals could facilitate both fructose dehydration and glucose isomerization via promoting the rate-limiting internal hydride shift, with the catalytic activity determined by its electronegativity, electron configuration, and charge density. Lewis acid site of a higher valence also enhanced hydrolysis of polysaccharide. However, the metals also catalyzed undesirable polymerization possibly by polarizing the carbonyl groups of sugars and derivatives, which should be minimized by process optimization.
Subject(s)
Food , Furaldehyde/analogs & derivatives , Metals , Waste Products , Carbohydrate Metabolism , Carbohydrates/chemistry , Catalysis , Furaldehyde/metabolism , Hydrolysis , Ions , Isomerism , Lewis Acids/metabolismABSTRACT
Cellulosic pulps have been successfully isolated from wheat straw through a Lewis acids organosolv treatment. The use of Lewis acids with different hardness produced pulps with different delignification degrees. The cellulosic residue was characterised by chemical composition, X-ray diffraction, FT-IR spectroscopy, N2 physisorption, scanning electron microscopy and potential for anaerobic digestibility. Surface area and pore volume increased with the hardness of the Lewis acid, in correspondence with the decrease of the amount of lignin and hemicellulose in the pulp. The non linearity of the correlation between porosity and composition suggests that an agglomeration of cellulose fibrils occurs in the early stages of pulping. All organosolv pulps presented a significantly higher methane potential than the parent straw. A methane evolution of 295Ncm(3)/g OM was reached by a moderate improvement of the accessibility of the native straw.
Subject(s)
Biotechnology/methods , Cellulose/metabolism , Lewis Acids/metabolism , Methane/biosynthesis , Triticum/chemistry , Waste Products , Adsorption , Biodegradation, Environmental , Crystallization , Lignin/metabolism , Polysaccharides/metabolism , Porosity , Spectroscopy, Fourier Transform Infrared , TemperatureABSTRACT
A direct, general and efficient method to synthesize 2H-chromenes (2H-benzo[b]pyrans), identified as environmentally friendly pesticides, has been developed. This approach lays on the new concept of ecocatalysis, which involves the use of biomass from phytoextraction processes, as a valuable source of metallic elements for chemical synthesis. This methodology is similar or superior to known methods, affording 2H-chromenes with good to excellent yields (60-98%), including the preparation of precocene I, a natural insect growth regulator, with 91% yield. The approach is ideal for poor reactive substrates such as phenol or naphthol, classically transformed into 2H-chromenes by methodologies associated with environmental issues. These results illustrate the interest of combining phytoextraction and green synthesis of natural insecticides.
Subject(s)
Biodegradation, Environmental , Environmental Pollutants/pharmacokinetics , Green Chemistry Technology/methods , Insecticides/chemical synthesis , Magnoliopsida/metabolism , Metals, Heavy/pharmacokinetics , Pest Control/methods , Benzopyrans/chemistry , Benzopyrans/metabolism , Cannabinoids/chemical synthesis , Cannabinoids/metabolism , Catalysis , Environmental Pollutants/analysis , Lewis Acids/chemistry , Lewis Acids/metabolism , Metals, Heavy/analysis , Molecular StructureABSTRACT
Among the phytotechnologies used for the reclamation of degraded mining sites, phytoextraction aims to diminish the concentration of polluting elements in contaminated soils. However, the biomass resulting from the phytoextraction processes (highly enriched in polluting elements) is too often considered as a problematic waste. The manganese-enriched biomass derived from native Mn-hyperaccumulating plants of New Caledonia was presented here as a valuable source of metallic elements of high interest in chemical catalysis. The preparation of the catalyst Eco-Mn1 and reagent Eco-Mn2 derived from Grevillea exul exul and Grevillea exul rubiginosa was investigated. Their unusual polymetallic compositions allowed to explore new reactivity of low oxidative state of manganese-Mn(II) for Eco-Mn1 and Mn(IV) for Eco-Mn2. Eco-Mn1 was used as a Lewis acid to catalyze the acetalization/elimination of aldehydes into enol ethers with high yields; a new green and stereoselective synthesis of (-)-isopulegol via the carbonyl-ene cyclization of (+)-citronellal was also performed with Eco-Mn1. Eco-Mn2 was used as a mild oxidative reagent and controlled the oxidation of aliphatic alcohols into aldehydes with quantitative yields. Oxidative cleavage was interestingly noticed when Eco-Mn2 was used in the presence of a polyol. Eco-Mn2 allowed direct oxidative iodination of ketones without using iodine, which is strongly discouraged by new environmental legislations. Finally, the combination of the properties in the Eco-Mn catalysts and reagents gave them an unprecedented potential to perform sequential tandem oxidation processes through new green syntheses of p-cymene from (-)-isopulegol and (+)-citronellal; and a new green synthesis of functionalized pyridines by in situ oxidation of 1,4-dihydropyridines.
Subject(s)
Biodegradation, Environmental , Green Chemistry Technology/methods , Lewis Acids/metabolism , Magnoliopsida/metabolism , Manganese/pharmacokinetics , Acyclic Monoterpenes , Alcohols/metabolism , Aldehydes/metabolism , Catalysis , Cymenes , Dihydropyridines/metabolism , Gas Chromatography-Mass Spectrometry , Hydrogen-Ion Concentration , Ketones/metabolism , Magnetic Resonance Spectroscopy , Manganese/chemistry , Monoterpenes/metabolism , New Caledonia , Oxidation-ReductionABSTRACT
Aryl-keto-containing α-amino acids are of great importance in organic chemistry and biochemistry. They are valuable intermediates for the construction of hydroxyl α-amino acids, nonproteinogenic α-amino acids, as well as other biofunctional components. Friedel-Crafts acylation is an effective method to prepare aryl-keto derivatives. In this review, we summarize the preparation of aryl-keto containing α-amino acids by Friedel-Crafts acylation using acidic α-amino acids as acyl-donors and Lewis acids or Brönsted acids as catalysts.
Subject(s)
Amino Acids, Acidic/chemistry , Lewis Acids/chemistry , Mesylates/chemistry , Acylation , Amino Acids, Acidic/metabolism , Catalysis , Lewis Acids/metabolism , Mesylates/metabolismABSTRACT
The activities of several Lewis acid catalysts such SnCl2, FeCl3, ZnCl2, AlCl3, and NbCl5 for the in situ transesterification/esterification of lipid contained within a microalga (Chlorella pyrenoidosa) in ethanol at 350°C were examined to identify the most suitable catalyst in term of crude biodiesel (CBD) yield. Of those catalysts tested, ZnCl2 showed the highest performance toward the CBD production. Using ZnCl2 as catalyst, effects of reaction temperature (200-370 °C), time (0-120 min), ethanol to microalga ratio (EtOH:MA) (5/5-40/5), catalyst loading (0-30 wt.%), and algae moisture (0-80 wt.%) on the yields of product fractions and the properties of CBD were studied. The presence of ZnCl2 not only promoted the production of CBD but also showed activities toward the deoxygenation and denitrogenation of CBD. The moisture content in the starting material is the most influential factor affecting the yield and properties of CBD.
Subject(s)
Chlorella/metabolism , Ethanol/metabolism , Lewis Acids/metabolism , Microalgae/metabolism , Biofuels/microbiology , Catalysis , Esterification , Gas Chromatography-Mass Spectrometry , Humidity , Temperature , Thermogravimetry , Time FactorsABSTRACT
Water or low molecular weight alcohols are, due to their availability, low price and low toxicity ideal reagents for organic synthesis. Recently, it was reported that, despite the very strong BDE of the O-H bond, they can be used as hydrogen atom donors in place of expensive and/or toxic group 14 metal hydrides when boron and titanium(III) Lewis acids are present. This finding represents a considerable innovation and uncovers a new perspective on the paradigm of hydrogen atom transfers to radicals. We discuss here the influence of complex formation and other association processes on the efficacy of the hydrogen transfer step. A delicate balance between activation by complex formation and deactivation by further hydrogen bonding is operative.
Subject(s)
Ethanol/chemistry , Free Radicals/chemistry , Hydrogen/chemistry , Lewis Acids/chemistry , Water/chemistry , Ethanol/metabolism , Hydrogen/metabolism , Hydrogen Bonding , Lewis Acids/metabolism , Models, Molecular , Molecular Structure , Water/metabolismABSTRACT
The Lewis acid-catalyzed domino 1,2-addition/1,4-addition/elimination between (Z)-3-hexene-2,5-dione and 1,3-dicarbonyls delivers 3-methyl-6,7-dihydrobenzofuran-4(5H)-ones exclusively with yields up to 82%. The combination of this new process with the laccase-catalyzed formation of (Z)-3-hexene-2,5-dione by oxidative cleavage of 2,5-dimethylfuran allows for the synthesis of 6,7-dihydrobenzofuran-4(5H)-ones starting directly from 2,5-dimethylfuran.
Subject(s)
Benzofurans/chemical synthesis , Benzofurans/metabolism , Cyclohexanones/chemistry , Furans/chemistry , Laccase/chemistry , Lewis Acids/chemistry , Benzofurans/chemistry , Catalysis , Crystallography, X-Ray , Cyclohexanones/metabolism , Furans/metabolism , Laccase/metabolism , Lewis Acids/metabolism , Models, Molecular , Molecular StructureABSTRACT
Results emanating from the synthesis of proanthocyanidins played a crucial role in defining the constitution, regiochemistry, and absolute configuration of this complex but fascinating group of plant secondary metabolites. The initial efforts, commencing in 1966, were focused on structure elucidation of, especially, the procyanidins, profisetinidins, and prorobinetinidins. However, over the past 12 years the emphasis has shifted to the synthesis of the bioactive procyanidins and some of their derivatives at a scale that would permit assessment of their pharmacological properties. With a few exceptions, the vast majority of these synthetic protocols involve the formation of the interflavanyl bond by acid/Lewis acid activation at C-4 of a flavan-3,4-diol or its equivalent, and subsequent trapping of the incipient C-4 carbocation by the nucleophilic centers of a flavan-3-ol (catechin). This review represents the first comprehensive chronicle depicting the development of the subject of proanthocyanidin synthesis.