Base-catalyzed Research Articles

Simulation-Guided Conformational Space Exploration to Assess Reactive Conformations of a Ribozyme.

Self-splicing ribozymes are small ribonucleic acid (RNA) enzymes that catalyze their own cleavage through a transphosphoesterification reaction. While this process is involved in some specific steps of viral RNA replication and splicing, it is also of importance in the context of the (putative) first autocatalytic RNA-based systems that could have preceded the emergence of modern life. The uncatalyzed phosphoester bond formation is thermodynamically very unfavorable, and many experimental studies have focused on understanding the molecular features of catalysis in these ribozymes. However, chemical reaction paths are short-lived and not easily characterized by experimental approaches, so molecular simulation approaches appear as an ideal tool to unveil the molecular details of the reaction. Here, we focus on the model hairpin ribozyme. We show that identifying a relevant initial conformation for reactivity studies, which is frequently overlooked in mixed quantum-classical studies that predominantly concentrate on the chemical reaction itself, can be highly challenging. These challenges stem from limitations in both available experimental structures (which are chemically altered to prevent self-cleavage) and the accuracy of force fields, together with the necessity for comprehensive sampling. We show that molecular dynamics simulations, combined with extensive conformational phase space exploration with Hamiltonian replica-exchange simulations, enable us to characterize the relevant conformational basins of the minimal hairpin ribozyme in the ligated state prior to self-cleavage. We find that what is usually considered a canonical reactive conformation with active site geometries and hydrogen-bond patterns that are optimal for the addition-elimination reaction with general acid/general base catalysis is metastable and only marginally populated. The thermodynamically stable conformation appears to be consistent with the expectations of a mechanism that does not require the direct participation of ribozyme residues in the reaction. While these observations may suffer from forcefield inaccuracies, all investigated forcefields lead to the same conclusions upon proper sampling, contrasting with previous investigations on shorter timescales suggesting that at least one reparametrization of the Amber99 forcefield allowed to stabilize aligned active site conformations. Our study demonstrates that identifying the most pertinent reactant state conformation holds equal importance alongside the accurate determination of the thermodynamics and kinetics of the chemical steps of the reaction.

Alkoxyalkylation of Electron-Rich Aromatic Compounds.

Alkoxyalkylation and hydroxyalkylation methods utilizing oxo-compound derivatives such as aldehydes, acetals or acetylenes and various alcohols or water are widely used tools in preparative organic chemistry to synthesize bioactive compounds, biosensors, supramolecular compounds and petrochemicals. The syntheses of such molecules of broad relevance are facilitated by acid, base or heterogenous catalysis. However, degradation of the N-analogous Mannich bases are reported to yield alkoxyalkyl derivatives via the retro-Mannich reaction. The mutual derivative of all mentioned species are quinone methides, which are reported to form under both alkoxy- and aminoalkylative conditions and via the degradation of the Mannich-products. The aim of this review is to summarize the alkoxyalkylation (most commonly alkoxymethylation) of electron-rich arenes sorted by the methods of alkoxyalkylation (direct or via retro-Mannich reaction) and the substrate arenes, such as phenolic and derived carbocycles, heterocycles and the widely examined indole derivatives.

Boosting biodiesel production from waste vegetable oil water using Acid-Base Sequential Catalysis

<p>The use of active and recyclable catalysts is advantageous for catalytic biodiesel synthesis from waste vegetable oils which is in demand owing to frequent calls on environmental pollution and for clean renewable energy production. For this study, homogenous catalysts are effective at converting single-origin feedstocks low in free fatty acids (FFA) and water into biodiesel. Biodiesel production based on waste vegetable oil was carried out to establish an optimal catalyst régime. Acid-catalyzed transesterification and sequential base catalysis were used to convert waste vegetable oil to biodiesel at varying amounts of catalyst (0.46-0.58%) and different contact times (1-2 hr). Optimal yields were obtained at 2 hrs contact time and 0.50% amount of catalyst. Characterization tests conducted were specific gravity (0.8718-0.8935), flash point (117-1370C), viscosity (4.29-6.09mm2/s) and cetane index (40-43) values were within biodiesel specifications. The study, therefore, confirmed that acid-base sequential catalysis holds a lot of promise for the creation of affordable, environmentally friendly technologies. The biodiesel's characteristics were also in good agreement with American (ASTM D6571) fuel specifications. Therefore, the work recommends the utilization of acid (H2SO4) and base (NaOH) catalysis in the technologically enhanced conversion of waste vegetable oil into biodiesel.</p>

Hypercrosslinked porous polymer as catalyst for efficient biodiesel production

While porous organic polymers (POPs) are known for their unique properties, their application in basic biodiesel catalysis is innovative. This study introduces a novel catalyst, hypercrosslinked polymer (HCP-SB-K), synthesized through mechanochemical polymerization of styrene and benzaldehyde with a cross-linking agent and FeCl3, followed by calcination of the previous polymer impregnated with KNO3. The synthesis costs 3.328 euros per gram of catalyst, covering energy and reagent expenses. The catalyst's basic character is explored, demonstrating efficient transesterification with diverse feedstocks. Under optimal conditions, the HCP-SB-K catalyst exhibits exceptional catalytic activity, yielding 99.9% FAME (Fatty Acid Methyl Esters) at 60 °C, 2 h and 3% w/w catalyst. Investigation of free fatty acid (FFA) content highlights the catalyst's effectiveness with oils varying FFA levels: oils with acid value of 0.44 mgKOH goil−1 reached 92.1% FAME at 60 °C, 1 h and 3% w/w catalyst; oils with an acid value of 1.11 mgKOH goil−1, reached 75.9% FAME, under the same conditions. Catalyst leaching evaluation indicates no discharge of basic sites. The regenerated catalyst (impregnation with KNO3 and calcination, after the first use) exhibits a 98.2% FAME like the fresh catalyst. This suggests that HCP-SB-K can be regenerated without noticeable deactivation, emphasizing its industrial potential.

Double layer silica antireflective films with high strength and rub resistance prepared by sol gel method

The single-layer silica antireflective film with base catalysis prepared by sol gel method is an important part of the high-power laser facility for inertial confinement fusion, while the weak adhesion between the single-layer silica film and the substrate during the preparation process makes it susceptible to be contacted erasure and unable to be used. Double-layer silica antireflective (DLAR) films of different thicknesses were obtained using the base catalysis sol–gel method, in which the upper layer was coated with a relatively dense thin layer, and the performances of the films were characterized. The results showed that the transmittances of the DLAR films with different thicknesses were ˃99.0%, and in which one of the maximum transmittance peaks reached to 99.83% @ 1000 nm. The surface roughness of the DLAR films was < 2.0 nm, and the surfaces of the films were flat. The contact angles between DLAR films and water reached 118° and maintained stable in high humidity environment. The laser induced damage thresholds for different thickness DLAR films (peak transmittances @ 400, 600, 800, 1000 nm) were comparable to device requirements by 1-on-1 testing method, and the DLAR films exhibited high strength and good friction resistance.Graphical abstract

Metal-free solid base catalysis: Boron-doped graphitic carbon nitride for the efficient synthesis of ethyl coumarin-3-carboxylate

In this work, boron doped graphitic carbon nitride materials (BgCN-x) were successfully prepared by thermal copolymerization of melamine and boric acid. The comprehensive characterization using various techniques, including powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR), UV-Visible spectroscopy (UV-Vis), Field emission scanning electron microscopy (FESEM), Energy-Dispersive X-ray spectroscopy (EDS), Field emission transmission electron microscopy (FETEM), and X-ray photoelectron spectroscopy (XPS) revealed the uniform doping of boron in the tri-s-triazine rings of g-C3N4 by substituting the carbon or nitrogen atoms. Furthermore, the basic site concentrations of the catalysts were evaluated using CO2-TPD technique. The BgCN catalysts exhibited significantly enhanced catalytic activity in the base-catalyzed Knoevenagel condensation between salicylaldehyde and diethyl malonate for coumarin synthesis. This work underscores the potential of boron-doped or two-dimensional boron-dominant materials as promising candidates for metal-free heterogeneous base catalysis, paving the way for further advancements in the field.

Metal and Ligand‐Free Approach Towards the Efficient One‐Pot Synthesis of Dipyridopyrimidinimine Derivatives

AbstractWe report a facile, expeditious, user‐friendly, and convenient metal‐free synthesis employing base catalysis in a one‐pot procedure to construct 11H‐dipyrido[1,2‐a : 3′,2′‐d]pyrimidin‐11‐imine derivatives. This protocol involves a domino process leading to the formation of double C−N bonds utilising KOtBu as the base and DMAc as the superior solvent at 25 °C for 2 h. The versatility of this methodology was demonstrated by its successful application to substrates with both electron‐withdrawing and electron‐donating functional groups, yielding novel functionalized stable 11H‐dipyrido[1,2‐a : 3′,2′‐d]pyrimidin‐11‐imine derivatives in good to excellent yields. Additionally, we have discussed a plausible reaction pathway for the synthesis.

Competing Reaction Mechanisms of Peptide Bond Formation in Water Revealed by Deep Potential Molecular Dynamics and Path Sampling.

The formation of an amide bond is an essential step in the synthesis of materials and drugs, and in the assembly of amino acids to form peptides. The mechanism of this reaction has been studied extensively, in particular to understand how it can be catalyzed, but a representation capable of explaining all the experimental data is still lacking. Numerical simulation should provide the necessary molecular description, but the solvent involvement poses a number of challenges. Here, we combine the efficiency and accuracy of neural network potential-based reactive molecular dynamics with the extensive and unbiased exploration of reaction pathways provided by transition path sampling. Using microsecond-scale simulations at the density functional theory level, we show that this method reveals the presence of two competing distinct mechanisms for peptide bond formation between alanine esters in aqueous solution. We describe how both reaction pathways, via a general base catalysis mechanism and via direct cleavage of the tetrahedral intermediate respectively, change with pH. This result contrasts with the conventional mechanism involving a single pathway in which only the barrier heights are affected by pH. We show that this new proposal involving two competing mechanisms is consistent with the experimental data, and we discuss the implications for peptide bond formation under prebiotic conditions and in the ribosome. Our work shows that integrating deep potential molecular dynamics with path sampling provides a powerful approach for exploring complex chemical mechanisms.

K2CO3-catalyzed highly efficient O and N-acylation under mild conditions

An eco-friendly, mild and efficient acylation of various nucleophiles with alkenyl carboxylates via inorganic base catalysis is described. Among five inorganic base species examined, K2CO3 was proved to be the most efficient catalyst for the acylation. A broad variety of acylated products were achieved within 15 min at room temperature in high yields. In addition, we found that the 3-position of indoles should have a suitable substituent group under this procedure.

Sustainable synthesis of chromene derivatives catalysed by magnetite nanoparticle cored polyamine dendrimer

Chromene derivatives are naturally occurring heterocyclic compounds used as cosmetic agents, food additives, and potential biodegradable agrochemicals. Normally, its synthesis is carried out with three component/substrates with a suitable base. Dendrimer with amine functionality has several applications in catalysis, more specifically, dendrimers having enriched amino groups with accessible void makes a significant impact in base catalysis. Moreover, polar periphery of the dendrimers may enhance the solubility of material in the reaction medium. Therefore, herein we report the base catalytic efficiency of magnetite nanoparticle supported polyamine dendrimer with enriched amine groups and peripheral carboxyl groups. Actually, magnetite supported polyamine dendrimer synthesis involves the synthesis of PAMAM G3 on magnetite nanoparticle core, followed by reduction of amide group with subsequent functionalization of carboxylic acid terminals. Further, it is used as versatile polyvalent base for the synthesis of chromene derivatives. The magnetite supported dendritic scaffold has accessible voids and polar periphery which enables them dispersible in the reaction medium. The recycle efficiency study confirms, the competency of the material to work in industrial catalysis.

Crystal structure of activating sulfotransferase SgdX2 involved in biosynthesis of secondary metabolite sungeidine

Microorganisms synthesize a plethora of complex secondary metabolites, many of which are beneficial to human health, such as anticancer agents and antibiotics. Among these, the Sungeidines are a distinct class of secondary metabolites known for their bulky and intricate structures. They are produced by a specific biosynthetic gene cluster within the genome of the soil-dwelling actinomycete Micromonospora sp. MD118. A notable enzyme in the Sungeidine biosynthetic pathway is the activating sulfotransferase SgdX2. In this pathway, SgdX2 mediates a key sulfation step, after which the product undergoes spontaneous dehydration to yield a Sungeidine compound. To delineate the structural basis for SgdX2's substrate recognition and catalytic action, we have determined the crystal structure of SgdX2 in complex with its sulfate donor product, 3′-phosphoadenosine 5′-phosphate (PAP), at a resolution of 1.6 Å. Although SgdX2 presents a compact overall structure, its core elements are conserved among other activating sulfotransferases. Our structural analysis reveals a unique substrate-binding pocket that accommodates bulky, complex substrates, suggesting a specialized adaptation for Sungeidine synthesis. Moreover, we have constructed a substrate docking model that provides insights into the molecular interactions between SgdX2 and Sungeidine F, enhancing our understanding of the enzyme's specificity and catalytic mechanism. The model supports a general acid-base catalysis mechanism, akin to other sulfotransferases, and underscores the minor role of disordered regions in substrate recognition. This integrative study of crystallography and computational modeling advances our knowledge of microbial secondary metabolite biosynthesis and may facilitate the development of novel biotechnological applications.

A method for basicity determination of thermally labile samples

BackgroundLayered double hydroxides (LDH) belong to the group of catalytic materials used in basic catalysis. Their basicity is the most important property for catalytic performance. Our work presents a possible method for the determination of such thermally labile materials' basicity using liquid phase sorption of a specific probe. ResultsAnthranilic acid was chosen as an optimal probe, and two methods were used for measuring the basic site amount – HPLC-MS and DRUV–Vis. The chosen methods described exactly the behavior of the tested LDHs in the model reaction. The basicity of LDHs increased in the row LDH2 < LDH3 < LDH2.5 which was the same trend for the conversion of reactant achieved in a model reaction. The important parameter in the model reaction and in the basicity determination was the particle size of the materials. The amount of adsorbed anthranilic acid on LDHs was in the range 197.8–199.7 mg/g, which was ten times higher than the amount adsorbed on mixed oxides (MO, the precursor for LDH preparation, adsorbed amount of anthranilic acid 13.8–18.5 mg/g). The MO adsorption of anthranilic acid showed differences in overall basicity that were not visible under conventionally used method (TPD). SignificanceThe developed method seems to be promising in the determination of the basicity of especially thermally labile materials for which the conventional methods cannot be used.

Catalytic Generation and Intermolecular Addition of Diarylmethyl Anions Utilizing [1,2]‐Phospha‐Brook Rearrangement Under Brønsted Base Catalysis

AbstractAn intermolecular addition reaction involving an unconventional combination of a diarylmethyl anion and an electrophile, which is mediated by the [1,2]‐phospha‐Brook rearrangement under Brønsted base catalysis, was developed. Diarylmethyl anions having a benzofuran moiety were generated through the rearrangement with the aid of a catalytic amount of phosphazene base P2‐tBu. The resulting carbanion intermediates were trapped by various electrophiles, such as α,β‐unsaturated ketones, aryl aldehydes, α‐ketoesters, and N‐Boc imines, providing the corresponding diarylalkane derivatives in good yields.

Palladium(0) π-Lewis Base Catalysis: Concept and Development.

The development of a new catalytic strategy plays a vital role in modern organic chemistry since it permits bond formation in an unprecedented and more efficient manner. Although the application of preformed metal complexes as π-base-activated reagents have enabled diverse transformations elegantly, the concept and strategy by directly utilizing transition metals as efficient π-Lewis base catalysts remain underdeveloped, especially in the field of asymmetric catalysis. Here, we outline our perspective on the discovery of palladium(0) as an efficient π-Lewis base catalyst, which is capable of increasing the highest occupied molecular orbital (HOMO) energy of both electron-neutral and electron-deficient 1,3-dienes and 1,3-enynes upon flexible η2-complexes formed in situ and resultant π-backdonation. Thus, fruitful carbon-carbon-forming reactions with diverse electrophiles can be achieved enantioselectively in a vinylogous addition pattern, which is conceptually different from the classical oxidative cyclization mechanism. Emphasis will be given to the concept and mechanism elucidation, catalytic features, and reaction design together with perspective on the further development of this emerging field.

Potassium tert‐Butoxide‐Catalyzed Selective Synthesis of 1,4‐Benzodioxepines via 7‐exo/7‐endo‐dig Cyclization of Alkynol: Experimental and DFT Study

AbstractA new method utilizing base catalysis is outlined for the synthesis of 1,4‐benzodioxepines, introducing a unique scaffold containing a seven‐membered ring heterocycle. The reaction proceeded under thermal conditions, with no waste was generated during the transformation, highlighting its remarkable atom efficiency and environmental friendliness. A straightforward metal‐free reaction condition utilizing 2‐propynyloxy benzyl alcohols as starting material and a catalytic amount of t‐BuOK in mesitylene at 100 °C for 1 hour was employed for this intramolecular cyclization transformation, resulting in the formation of 1,4‐Benzodioxepines in good to excellent yields and high regio‐ and diastereo‐selectivity. The density functional theory (DFT) calculations yielded the relative internal energy (U), enthalpy (H), and Gibbs free energy (G) values for all possible products, aligning closely with our experimental data.

Comprehensive understanding of base catalysis derived from nitrogen species incorporated into the frameworks of silica and carbon porous materials

A base-catalytic nitrogen site in a specific and confined nanospace on the surfaces of silica and carbon was developed using mesoporous silica SBA-15 and its replicated porous carbon nitride PCN. Knoevenagel condensation reactions using differentially active methylene compounds and diffusion studies using CO2 as the probe molecule for the basic site revealed that the primary amine-based N component showed high activity for the base-catalyzed reaction. Among the samples investigated, primary amine-grafted SBA-15 showed the highest performance owing to the activity and location density of primary amines, as well as its surrounding hydrophobic nature. Although NSBA-15 showed moderate catalytic performance owing to an isolated active N species located on its mesopore surface, methylation of the N species led to enhanced catalytic performance because of its isolation effect. Carbonaceous PCN showed high hydrophobicity and durability during reaction and storage. A general design for N-based basic catalytic materials was also proposed.

Bifunctional two-dimensional copper-organic framework for high catalytic performance on cycloaddition of CO2 with epoxides and deacetalization-Knoevenagel condensation

Due to the larger external surface areas and more accessible active sites, two-dimensional (2D) metal-organic frameworks (MOFs) have aroused great interest in the catalytic field. Herein, the exquisite combination of Cu2+ and designed flexible tetracarboxylic acid of 1,1′-(1,3-phenylenebis(methylene))bis(1H-benzo[d]imidazole-5,6-dicarboxylic acid) (H4PBDA) under the solvothermal condition offers a highly robust 2D network of [Cu(H2PBDA)(H2O)]n (NUC-130), which are interlaced via hydrogen-bonding interactions to form a 3D skeleton. After removing associated solvent molecules by activation, NUC-130a is a scarcely reported Lewis acid/Brönsted acid mediated host framework, which can serve as a promising multifunctional catalyst due to the plentiful active sites including exposed penta-coordinated Cu2+ ions, Brønsted acidic sites of -COOH, and Lewis basic sites of Nbenzimidazole atoms and C=O groups. Performed experiments confirmed that NUC-130a had the high catalytic performance on the cycloaddition of CO2 with a series of epoxide derivatives under solvent-free mild conditions. Furthermore, for deacetalization-Knoevenagel condensation based on acid-base catalysis, NUC-130a also shows excellent catalytic activity, which should be ascribed to that dimethyl acetal can be more effectively hydrolyzed by free -COOH group into formyl group than simple Lewis acidic metal sites. Hence, this work not only provides a type of promising catalyst for efficient chemical fixation of CO2 and deacetalization-Knoevenagel condensation, but also opens up an avenue to creating multifunctional MOFs with integrating multiple active sites and larger external surface areas.

Facile Synthesis of Quinoline-Substituted 3-Hydroxy-2-oxindoles and 3-Amino-2-oxindoles via a Palladium-Catalyzed Cascade Intramolecular Cyclization/Intermolecular Nucleophilic Addition Reaction.

An efficient cascade intramolecular cyclization/intermolecular nucleophilic addition reaction of allenyl benzoxazinone with isatin or isatin-derived ketimine has been established by using Pd0-π-Lewis base catalysis. A series of 3-hydroxy-2-oxindoles and 3-amino-2-oxindoles with quaternary carbon atoms at the C3 position were synthesized in good yields under mild conditions through this protocol.

Flavin-N5OOH Functions as both a Powerful Nucleophile and a Base in the Superfamily of Flavoenzymes.

Flavoenzymes can mediate a large variety of oxidation reactions through the activation of oxygen. However, the O2 activation chemistry of flavin enzymes is not yet fully exploited. Normally, the O2 activation occurs at the C4a site of the flavin cofactor, yielding the flavin C4a-(hydro)hydroperoxyl species in monooxygenases or oxidases. Using extensive MD simulations, QM/MM calculations and QM calculations, our studies reveal the formation of the common nucleophilic species, Flavin-N5OOH, in two distinct flavoenzymes (RutA and EncM). Our studies show that Flavin-N5OOH acts as a powerful nucleophile that promotes C-N cleavage of uracil in RutA, and a powerful base in the deprotonation of substrates in EncM. We reason that Flavin-N5OOH can be a common reactive species in the superfamily of flavoenzymes, which accomplish generally selective general base catalysis and C-X (X=N, S, Cl, O) cleavage reactions that are otherwise challenging with solvated hydroxide ion base. These results expand our understanding of the chemistry and catalysis of flavoenzymes.

Flavin‐N5OOH Functions as both a Powerful Nucleophile and a Base in the Superfamily of Flavoenzymes

AbstractFlavoenzymes can mediate a large variety of oxidation reactions through the activation of oxygen. However, the O2 activation chemistry of flavin enzymes is not yet fully exploited. Normally, the O2 activation occurs at the C4a site of the flavin cofactor, yielding the flavin C4a‐(hydro)hydroperoxyl species in monooxygenases or oxidases. Using extensive MD simulations, QM/MM calculations and QM calculations, our studies reveal the formation of the common nucleophilic species, Flavin‐N5OOH, in two distinct flavoenzymes (RutA and EncM). Our studies show that Flavin‐N5OOH acts as a powerful nucleophile that promotes C−N cleavage of uracil in RutA, and a powerful base in the deprotonation of substrates in EncM. We reason that Flavin‐N5OOH can be a common reactive species in the superfamily of flavoenzymes, which accomplish generally selective general base catalysis and C−X (X=N, S, Cl, O) cleavage reactions that are otherwise challenging with solvated hydroxide ion base. These results expand our understanding of the chemistry and catalysis of flavoenzymes.