Class Of Substrates Research Articles

Cápsulas biodegradáveis podem ampliar a germinação de sementes de espécies florestais do Cerrado

ABSTRACT: A good grasp of the different facets of seed germination of the plant species native to the Cerrado will facilitate the selection of species that can be used to restore degraded ecosystems. Hence, the objective of the current study was to confirm the ways biodegradable capsules affect the germination of the seeds of three tree species typical of the physiognomies of the Cerrado forest (Enterolobium contortisiliquum, Anadenanthera colubrina and Dipteryx alata). The experiments, conducted in a greenhouse, included two treatments: seeding performed inside biodegradable capsules and direct seeding on the substrate surface. Two seeds from each of the species were sown in plastic bags containing the Quartzarenic Neosol class of substrates. Using five replicates for each treatment resulted in 20 plastic bags for each. The greenhouse conditions included controlled temperature and relative humidity. Inside the capsules, the findings revealed that the baru, angico-branco and tamboril seeds germinated at the rates of 97%, 42%, and 12%, respectively. However, during direct seeding, germination rates for baru, angico-branco and tamboril were 15%, 21% and 8%. From the findings, it is evident that when biodegradable capsules are used, the germination of all three Cerrado species investigated is favoured. Thus, both capsules and the cited species can be recommended for projects of ecological restoration.

N-Heterocyclic carbene (NHC) organocatalysis: from fundamentals to frontiers.

N-Heterocyclic carbenes (NHCs) have been used as organocatalysts for a multitude of C-C and C-heteroatom bond-forming reactions. They enable diverse modalities of activating a wide range of structurally distinct substrate classes and allow access to electronically distinct intermediates. The easy tunability of the NHC scaffold contributes to its versatility. Recent years have witnessed a surge of interest in various organocatalytic reactions of NHCs, leading to the forays of NHC catalysis into the relatively newer domains such as reactions involving radical intermediates, atroposelective synthesis, umpolung of electrophiles other than aldehydes, and the use of NHCs as non-covalent templates for enantioinduction. This tutorial review provides an overview of various important structural features and reactivity modes of NHCs and delves deep into some frontiers of NHC-organocatalysis.

Design of Chemoresponsive Liquid Crystals Using Metal-Coordinating Polymer Surfaces.

Liquid crystals (LCs), when interfaced with chemically functionalized surfaces, can amplify a range of chemical and physical transformations into optical outputs. While metal cation-binding sites on surfaces have been shown to provide a basis for the design of chemoresponsive LCs, the cations have been found to dissociate from the surfaces and dissolve slowly into LCs, resulting in time-dependent changes in the properties of LC-solid interfaces (which impacts the reliability of devices incorporating such surfaces). Here, we explore the use of surfaces comprising metal-coordinating polymers to minimize the dissolution of metal cations into LCs and characterize the impact of the interfacial environment created by the coordinating polymer on the ordering and time-dependent properties of LCs. In particular, by combining theoretical (electronic structure calculations) and experimental (polarization-modulation infrared reflection-adsorption spectroscopy) results, we determine that the pyridine groups of a thin film of poly(4-vinylpyridine-co-divinylbenzene) (P(4VP-co-DVB)) coordinate with Ni2+ when Ni(ClO4)2 is deposited onto the film. We provide evidence that the Ni2+-pyridine coordination weakens the binding of Ni2+ with 4'-n-pentyl-4-biphenylcarbonitrile (5CB), a room-temperature nematic LC, as compared to Ni(ClO4)2 supported on glass, although binding is still sufficiently strong to induce a homeotropic (perpendicular) orientation of the LC. Exposure of the 5CB films supported on Ni(ClO4)2-decorated P(4VP-co-DVB) substrates to parts-per-million vapor concentrations of dimethylmethylphosphonate (DMMP) was found to trigger orientational transitions (to planar (parallel) orientations) in the LC films. In contrast, 5CB supported on Ni(ClO4)2-decorated glass surfaces exhibited no response, even though displacement of 5CB by DMMP is predicted by computations to be thermodynamically favored in both cases. We propose that the distinct LC responses measured on glass and the coordinating polymer substrates are governed by the kinetics of displacement of 5CB by DMMP, a proposal that is supported by measurements performed with increasing temperature. Importantly, by using Ni2+ supported on P(4VP-co-DVB), we measured the ordering of 5CB to be stable and long-lived (>7 days), in contrast to unstable LC ordering (<14 h) when using Ni2+ supported on glass under dry conditions and at room temperature. We further demonstrate the stability of Ni(ClO4)2 supported on P(4VP-co-DVB) toward higher temperatures and humidity using E7 as the LC. Overall, these results demonstrate that metal-coordinating polymer films are a promising class of substrates for fabricating robust and long-lived chemoresponsive LCs.

From gem‐Dichlorocyclobutenones to Cyclobutenols: Unveiling a Ruthenium‐Catalyzed Allylic Reduction‐Asymmetric Transfer Hydrogenation Cascade

AbstractCyclobutenones constitute an appealing class of substrates in catalytic asymmetric transformations leading to diversely substituted enantioenriched four‐membered carbocycles, which are eliciting a growing interest in medicinal chemistry. Whilst several synthetically useful enantioselective conjugate addition reactions have been reported, the catalytic enantioselective reduction of the carbonyl group of simple cyclobutenones remains an elusive transformation. Herein, we disclose the discovery of a novel allylic reduction‐asymmetric transfer hydrogenation cascade, catalyzed by a Noyori‐Ikariya ruthenium complex, from readily available gem‐dichlorocyclobutenones, leading to 2‐chlorocyclobutenols with high optical purities, which can be engaged in postfunctionalization reactions enabling access to substituted four‐membered rings.

Site-Selective O-Arylation of Carbohydrate Derivatives through Nickel-Photoredox Catalysis.

Site-selective O-arylations of glycoside-derived diols have been achieved by couplings with bromoarenes upon irradiation with blue LEDs in the presence of an iridium photocatalyst and a nickel complex. The use of hexamethylenetetramine (hexamine) in place of quinuclidine, along with the application of a methoxy-substituted 2,2'-bipyridine ligand, provided improvements in yield for this relatively challenging substrate class. Selective arylation took place at the less sterically hindered OH group, as determined by the substitution pattern and configuration of the glycoside substrate. Percent buried volume calculations were used to quantify the relative levels of steric hindrance at the two reactive sites.

Artificial Gold Enzymes Using a Genetically Encoded Thiophenol‐Based Noble‐Metal‐Binding Ligand

AbstractIncorporating noble metals in artificial metalloenzymes (ArMs) is challenging due to the lack of suitable soft coordinating ligands among natural amino acids. We present a new class of ArMs featuring a genetically encoded noble‐metal‐binding site based on a non‐canonical thiophenol‐based amino acid, 4‐mercaptophenylalanine (pSHF), incorporated in the transcriptional regulator LmrR through stop codon suppression. We demonstrate that pSHF is an excellent ligand for noble metals in their low oxidation states. The corresponding gold(I) enzyme was characterised by mass spectrometry, UV/Vis spectroscopy and X‐ray crystallography and successfully catalysed hydroamination reactions of 2‐ethynyl anilines with turnover numbers over 50. Interestingly, two equivalents of gold(I) per protein dimer proved to be required for activity. Up to 98 % regioselectivity in the hydroamination of an ethynylphenylurea substrate was observed, yielding the corresponding phenyl‐dihydroquinazolinone product, consistent with a π‐activation mechanism by single gold centres. The ArM was optimized by site saturation mutagenesis using an on‐bead screening protocol. This resulted in a single mutant that showed higher activity for one class of substrates. This work brings the power of noble‐metal catalysis into the realm of enzyme engineering and establishes thiophenols as alternative ligands for noble metals, providing new opportunities in coordination chemistry and catalysis.

Defect-Engineered Coordination Compound Nanoparticles Based on Prussian Blue Analogues for Surface-Enhanced Raman Spectroscopy.

Surface-enhanced Raman spectroscopy (SERS) is a powerful tool for label-free chemical analysis. The emergence of nonmetallic materials as SERS substrates, offering chemical signal enhancements, presents an exciting direction for achieving reproducible and biocompatible SERS, a challenge with traditional metallic substrates. Despite the potential, the realm of nonmetallic SERS substrates, particularly nanoparticles, remains largely untapped. Here, we present defect-engineered coordination compounds (DECCs) based on Prussian blue analogues (PBAs) as a class of nonmetallic nanoparticle-based SERS substrates. We demonstrate the utility and flexibility of the DECC template by incorporating various metal (M) elements into PBAs to synthesize nanoparticles that deliver substantial chemical mechanism (CM)-based enhancements to the Raman signal with a ∼ 108-fold increase. The introduction of the M-PBA-based DECC nanoparticles as a class of SERS substrates represents a pioneering stride, enabling the straightforward and systematic exploration of a library of compounds for SERS-based analysis of a wide range of target molecules, especially biomolecules.

Isothiourea‐Catalysed Acylative Kinetic Resolution of Tertiary Pyrazolone Alcohols

AbstractThe development of methods for the selective acylative kinetic resolution (KR) of tertiary alcohols is a recognised synthetic challenge with relatively few successful substrate classes reported to date. In this manuscript, a highly enantioselective isothiourea‐catalysed acylative KR of tertiary pyrazolone alcohols is reported. The scope and limitations of this methodology have been developed, with high selectivity observed across a broad range of substrate derivatives incorporating varying substitution at N(2)‐, C(4)‐ and C(5)‐, as well as bicyclic constraints within the pyrazolone scaffold (30 examples, selectivity factors (s) typically &gt;100) at generally low catalyst loadings (1 mol %). The application of this KR method to tertiary alcohols derived directly from a natural product (geraniol), alongside pharmaceutically relevant drug compounds (indomethacin, gemfibrozil and probenecid), with high efficiency (s &gt;100) is also described. The KR process is readily amenable to scale up using bench grade solvents and reagents, with effective resolution on a 50 g (0.22 mol) scale demonstrated. The key structural motif leading to excellent selectivity in this KR process has been probed through computation, with an NC=O⋅⋅⋅isothiouronium interaction from substrate to acylated catalyst observed within the favoured transition state. Similarly, the effect of C(5)‐aryl substitution that leads to reduced experimental selectivity is probed, with a competitive π–isothiouronium interaction identified as leading to reduced selectivity.

Isothiourea-Catalysed Acylative Kinetic Resolution of Tertiary Pyrazolone Alcohols.

The development of methods for the selective acylative kinetic resolution (KR) of tertiary alcohols is a recognised synthetic challenge with relatively few successful substrate classes reported to date. In this manuscript, a highly enantioselective isothiourea-catalysed acylative KR of tertiary pyrazolone alcohols is reported. The scope and limitations of this methodology have been developed, with high selectivity observed across a broad range of substrate derivatives incorporating varying substitution at N(2)-, C(4)- and C(5)-, as well as bicyclic constraints within the pyrazolone scaffold (30 examples, selectivity factors (s) typically >100) at generally low catalyst loadings (1 mol%). The application of this KR method to tertiary alcohols derived from a natural product (geraniol), alongside pharmaceutically relevant drug compounds (indomethacin, gemfibrozil and probenecid), with high efficiency (s > 100) is also described. The KR process is readily amenable to scale up, with effective resolution on a 50 g (0.22 mol) scale demonstrated. The key structural motif leading to excellent selectivity in this KR process has been probed through computation, with an NC=O•••isothiouronium interaction observed within the favoured transition state. Similarly, the effect of C(5)-aryl substitution that leads to reduced experimental selectivity is probed, with a competitive π-isothiouronium interaction identified as leading to reduced selectivity.

Quantitative Reactivity Models for Oxidative Addition to L2Pd(0): Additional Substrate Classes, Solvents, and Mechanistic Insights.

Quantitative molecular structure-reactivity models are useful for generating predictions to guide synthesis design, and in formulating and testing mechanistic hypotheses. We report an expanded multivariate linear regression (MLR) model for the rate of (hetero)aryl (pseudo)halide oxidative addition to L2Pd(0), here exemplified by Pd(PCy3)2. This builds on a prior model from our group, with additional substrate classes (aryl chlorides and iodides) and reaction solvents (THF, toluene, THF/DMF mixture). Overall solvent effects across the entire substrate set are minimal under these conditions, enabling a unified MLR model without introduction of new molecular descriptors beyond the original five. Examining the mechanistic origin of the two molecular electrostatic potential (ESP) descriptors led to generation of a simpler, four descriptor model that is suitable for aryl halides, but not for 2-halopyridines. Using this model we identified a mechanistic outlier, 2-pyridyl triflate, which undergoes a nucleophilic displacement oxidative addition that does not involve the adjacent nitrogen atom. Finally, we discuss the relationship between C-X bond strength and oxidative addition rates, and compare the intrinsic bond strength index (IBSI) to bond dissociation enthalpy (BDE) as a bond strength descriptor.

Highly Acidic Electron-Rich Brønsted Acids Accelerate Asymmetric Pictet-Spengler Reactions by Virtue of Stabilizing Cation-π Interactions.

Electron-rich heteroaromatic imidodiphosphorimidates (IDPis) catalyze the asymmetric Pictet-Spengler reaction of N-carbamoyl-β-arylethylamines with high stereochemical precision. This particular class of catalysts furthermore provides a vital rate enhancement compared to related Brønsted acids. Here we present experimental studies on the underlying reaction kinetics that shed light on the specific origins of rate acceleration. Analysis of Hammett plots, kinetic isotope effects, reaction orders, Eyring plots, and isotopic scrambling experiments, allowed us to gather insights into the molecular interactions between the chiral Brønsted acid and catalytically formed intermediates. Based on rigorously determined pKa values as well as the experimental evidence, we propose that attractive intermolecular forces offered by electron-rich π-surfaces of the chiral counteranion enthalpically stabilize cationic intermediates and transition states by way of cation-π interactions. This view is furthermore supported by in-depth density functional theory calculations. Our deepened understanding of the reaction mechanism allowed us to develop a method for accessing 1-aryltetrahydroisoquinolines from aromatic dimethyl acetals, a substrate class that was thus far inaccessible via catalytic asymmetric Pictet-Spengler reactions.

Reaction of acetylenic carbanions with C=N bond: dynamics of development, synthetic divergence, environmental safety

This review highlights dynamics of development and synthetic application of the recently discovered reaction of acetylenic carbanions, generated in superbase media, with C=N bond of different classes of substrates. A fundamental feature of this reaction is its synthetic divergence, i.e. its ability to proceed in various directions that manifests in novel transformations to selectively deliver (depending on structure of the acetylenes and substrates with C=N bond) structurally different synthetically important products. The review also discusses cascade processes, in which the key intermediates containing the C=N bond add acetylenes thereby participating in the self-organization of diverse and potentially useful compounds. The competitive advantage of the reaction and its daughter branches is environmental safety (neutrality), based on the fundamental chemical nature of these reactions as addition processes that occur without the release of by-products.&lt;br&gt; The bibliography includes 133 references.

Enantioselective Transfer Hydrogenation of α-Methoxyimino-β-keto Esters.

α-Methoxyimino-β-keto esters are reported to undergo highly enantioselective catalytic transfer hydrogenation using the Noyori-Ikariya complex RuCl(p-cymene)[(S,S)-Ts-DPEN] in a mixture of formic acid-triethylamine and dimethylformamide at 25 °C. The experimental study performed on over 25 substrates combined with computational analysis revealed that a Z-configured methoxyimino group positioned alpha to a ketone carbonyl leads to higher reactivity and mostly excellent enantioselectivity within this substrate class. Density functional theory calculations of competing transition states were used in rationalizing the origins of enantioselectivity and the possible role of the methoxyimino group in the reaction outcome.

Raman enhancement via double optical resonances in all-dielectric photonic crystal slabs

All-dielectric photonic structures are an important class of substrates in surface-enhanced Raman spectroscopy (SERS), utilizing optical resonant modes to significantly enhance the electromagnetic field and amplify the Raman signals. In this study, we demonstrate the double-resonance approach to realize significant Raman enhancement using all-dielectric photonic crystal (PhC) slab. The double-resonance condition is satisfied by designing optical resonant modes in photonic bands to match frequencies of both excitation laser and Raman signals. By the fabricated PhC slab, the significant enhancement for the Raman signal of silicon is demonstrated. The enhanced Raman signals exhibit a uniform distribution on the PhC slab. The method of Raman enhancement via double optical resonances can advance the field of all-dielectric SERS and holds potential for future SERS applications.

Sulfotransferase-mediated phase II drug metabolism prediction of substrates and sites using accessibility and reactivity-based algorithms.

Sulphotransferases (SULTs) are a major phase II metabolic enzyme class contributing ~20 % to the Phase II metabolism of FDA-approved drugs. Ignoring the potential for SULT-mediated metabolism leaves a strong potential for drug-drug interactions, often causing late-stage drug discovery failures or black-boxed warnings on FDA labels. The existing models use only accessibility descriptors and machine learning (ML) methods for class and site of sulfonation (SOS) predictions for SULT. In this study, a variety of accessibility, reactivity, and hybrid models and algorithms have been developed to make accurate substrate and SOS predictions. Unlike the literature models, reactivity parameters for the aliphatic or aromatic hydroxyl groups (R/Ar-O-H), the Bond Dissociation Energy (BDE) gave accurate models with a True Positive Rate (TPR)=0.84 for SOS predictions. We offer mechanistic insights to explain these novel findings that are not recognized in the literature. The accessibility parameters like the ratio of Chemgauss4 Score (CGS) and Molecular Weight (MW) CGS/MW and distance from cofactor (Dis) were essential for class predictions and showed TPR=0.72. Substrates consistently had lower BDE, Dis, and CGS/MW than non-substrates. Hybrid models also performed acceptablely for SOS predictions. Using the best models, Algorithms gave an acceptable performance in class prediction: TPR=0.62, False Positive Rate (FPR)=0.24, Balanced accuracy (BA)=0.69, and SOS prediction: TPR=0.98, FPR=0.60, and BA=0.69. A rule-based method was added to improve the predictive performance, which improved the algorithm TPR, FPR, and BA. Validation using an external dataset of drug-like compounds gave class prediction: TPR=0.67, FPR=0.00, and SOS prediction: TPR=0.80 and FPR=0.44 for the best Algorithm. Comparisons with standard ML models also show that our algorithm shows higher predictive performance for classification on external datasets. Overall, these models and algorithms (SOS predictor) give accurate substrate class and site (SOS) predictions for SULT-mediated Phase II metabolism and will be valuable to the drug discovery community in academia and industry. The SOS predictor is freely available for academic/non-profit research via the GitHub link.

Nature-Inspired Radical Pyridoxal-Mediated C-C Bond Formation.

Pyridoxal-5'-phosphate (PLP) and derivatives of this cofactor enable a plethora of reactions in both enzyme-mediated and free-in-solution transformations. With few exceptions in each category, such chemistry has predominantly involved two-electron processes. This sometimes poses a significant challenge for using PLP to build tetrasubstituted carbon centers, especially when the reaction is reversible. The ability to access radical pathways is paramount to broadening the scope of reactions catalyzed by this coenzyme. In this study, we demonstrate the ability to access a radical PLP-based intermediate and engage this radical intermediate in a number of C-C bond-forming reactions. By selection of an appropriate oxidant, single-electron oxidation of the quinonoid intermediate can be achieved, which can subsequently be applied to C-C bond-forming reactions. Through this radical reaction pathway, we synthesized a series of α-tertiary amino acids and esters to investigate the substrate scope and identify nonproductive reaction pathways. Beyond the amino acid model system, we demonstrate that other classes of amine substrates can be applied in this reaction and that a range of small molecule reagents can serve as coupling partners to the semiquinone radical. We anticipate that this versatile semiquinone radical species will be central to the development of a range of novel reactions.

Chemogenetic Evolution of Diversified Photoenzymes for Enantioselective [2 + 2] Cycloadditions in Whole Cells.

Artificial photoenzymes with novel catalytic modes not found in nature are in high demand; yet, they also present significant challenges in the field of biocatalysis. In this study, a chemogenetic modification strategy is developed to facilitate the rapid diversification of photoenzymes. This strategy integrates site-specific chemical conjugation of various artificial photosensitizers into natural protein cavities and the iterative mutagenesis in cell lysates. Through rounds of directed evolution, prominent visible-light-activatable photoenzyme variants were developed, featuring a thioxanthone chromophore. They successfully enabled the enantioselective [2 + 2] photocycloaddition of 2-carboxamide indoles, a class of UV-sensitive substrates that are traditionally challenging for known photoenzymes. Furthermore, the versatility of this photoenzyme is demonstrated in enantioselective whole-cell photobiocatalysis, enabling the efficient synthesis of enantioenriched cyclobutane-fused indoline tetracycles. These findings significantly expand the photophysical properties of artificial photoenzymes, a critical factor in enhancing their potential for harnessing excited-state reactivity in stereoselective transformations.

MECHANISM OF DEPROTONATION OF THE AMINO GROUP OF GLUTAMATE UPON BINDING TO N-ACETYLGLUTAMATE SYNTHASE

Gcn5-related N-acetyltransferases catalyze the transfer of an acetyl group to a primary amino group of a wide class of substrates. Protonation of the amino group upon binding to the enzyme is necessary to activate the nucleophilic attack on the substrate. The process of glutamate binding to N-acetylglutamate synthase is considered using molecular modeling and quantum chemistry methods. It has been shown that deprotonation of the primary amino group of glutamate occurs upon binding to the active site of the enzyme with the participation of the side chain of the aspartate residue.

Engineering of Rieske dioxygenase variants with improved cis-dihydroxylation activity for benzoates.

Rieske dioxygenases have a long history of being utilized as green chemical tools in the organic synthesis of high-value compounds, due to their capacity to perform the cis-dihydroxylation of a wide variety of aromatic substrates. The practical utility of these enzymes has been hampered however by steric and electronic constraints on their substrate scopes, resulting in limited reactivity with certain substrate classes. Herein, we report the engineering of a widely used member of the Rieske dioxygenase class of enzymes, toluene dioxygenase (TDO), to produce improved variants with greatly increased activity for the cis-dihydroxylation of benzoates. Through rational mutagenesis and screening, TDO variants with substantially improved activity over the wild-type enzyme were identified. Homology modeling, docking studies, molecular dynamics simulations, and substrate tunnel analysis were applied in an effort to elucidate how the identified mutations resulted in improved activity for this polar substrate class. These analyses revealed modification of the substrate tunnel as the likely cause of the improved activity observed with the best-performing enzyme variants.

Phosphorus Content of Several Plant-Based Yogurts

ObjectiveIn people with chronic kidney disease (CKD), hyperphosphatemia is an independent risk factor for mortality in observational studies. Despite not having proven benefit, dietary control of phosphorus is thought to be essential in CKD. Though dietary and serum phosphorus are correlated, ingested phosphate is less bioavailable from plant-foods rich in phytate than from animal and processed foods. Yogurt is considered a useful food due to its relatively low phosphorus and high protein content but may be detrimental since the protein content is from animal sources. Instead, plant-based yogurts (PBYs) may offer similar benefits without the associated downsides of animal protein in kidney disease, but little is known about the phosphorus contents of PBYs. Design and MethodsProtein contents and phosphorus additives were obtained from nutrition labels of several, widely available PBYs of almond, cashew, oat, coconut, and soy substrates. Phosphorus content was measured via emission spectrometry by Eurofins (Madison, WI). Based on these data, phosphorus-to-protein ratio (PPR) for each PBY was calculated. ResultsPhosphorus was highest in Silk Soy Strawberry, then Silk Almond Strawberry and Siggi’s Coconut Mixed Berries. Phosphorus was lowest in So Delicious Coconut Strawberry, then Oatly Oat Strawberry, Forager Cashew Strawberry, and Kite Hill Almond Strawberry. According to the ingredient labels, Silk Soy Strawberry, Silk Almond Strawberry, and Oatly Oat Strawberry contained phosphorus additives while Siggi’s Coconut Mixed Berries contained pea protein additives. Of PBYs from the same substrate class, So Delicious Coconut Strawberry and Siggi’s Coconut Mixed Berries had the largest differences in their phosphorus and protein contents. These seven samples’ PPR ratios were higher than that of dairy yogurt values reported from the literature, including Stonyfield Organic Oikos Strawberry, Chobani Nonfat Strawberry, and Yoplait Greek Strawberry. ConclusionLow phosphorus-to-protein ratio (PPR) foods are emphasized for people with CKD. Siggi’s Coconut Mixed Berries had the lowest PPR. However, So Delicious Coconut Strawberry had the highest ratio which underscores product variability despite both using the same PBY substrate. Of the samples analyzed, Siggi’s Coconut Mixed Berries may be the most desirable for patients with CKD because its PPR was the lowest.