Small Molecule Transformations Research Articles

Aminosilane@mesoporoussilica/chitosan∗salicylaldehyde nanohybrid: synthesis, characterization and applications

“Hydrogen-borrowing” mechanism has enables the production of biologically active molecules with minimal waste, high efficiency and mild reaction conditions. However, majority of research on the above mechanism has been focused on small molecule transformations. Hence, using Fe-tetraphenylcyclopentadienone tricarbonyl complex as a catalyst for “hydrogen-borrowing” mechanism between amines and alcohols, a novel pH-responsive inorganic-organic hybrid nanocarrier based on mesoporous silica-chitosan (MSN@CONH2/CS∗SCA) was developed to overcome these limitations. The nanocarrier was fabricated through C-N bond formation between 1-[3-trimethoxysiliylpropyl] urea functionalized mesoporous silica and salicylaldehyde modified chitosan derivative for antibacterial, antioxidant and drug delivery application. The chemical composition of synthesized nanocarrier was characterized by FTIR, 1H NMR and XRD techniques while the thermal stability examined through TGA. The surface morphology and porosity were evaluated using BET, SEM, and TEM whereas elemental composition, particle size and surface charge were determined by EDX with mapping, PSA and Zeta-potential method respectively. The nanohybrid was loaded with quercetin and curcumin drug, with 82.68 % and 83.24 % encapsulation efficiency respectively. The controlled drug release for quercetin was observed with 76 % (pH-5.0) and 20 % (pH-7.4), while for curcumin it observed 70.36 % (pH-5.0) and 19.16 % (pH-7.4) in 72 h. The antibacterial performance of nanocarrier shows better zone of inhibition for E. coli [2.9 ± 0.2 cm(3)] as compared to B. subtilis [1.6 ± 0.3 cm(3)]. The antioxidant ability of nano-hybrid to scavenge DPPH and ABTS radicals were 53.18 % and 55.21 %, respectively. Thereafter, MTT cytotoxicity assay of nanohybrid on peripheral blood mononuclear cells) exhibited promising results for biomedical applications.

Small Molecule Activation at the acriPNP Pincer-Supported Nickel Sites.

ConspectusNickel pincer systems have recently attracted much attention for applications in various organometallic reactions and catalysis involving small molecule activation. Their exploration is in part motivated by the presence of nickel in natural systems for efficient catalysis. Among such systems, the nickel-containing metalloenzyme carbon monoxide dehydrogenase (CODH) efficiently and reversibly converts CO2 to CO at its active site. The generated CO moves through a channel from the CODH active site and is transported to a dinuclear nickel site of acetyl-coenzyme A synthase (ACS), which catalyzes organometallic C-S and C-C bond forming reactions. An analogous C-S bond activation process is also mediated by the nickel containing enzyme methyl-coenzyme M reductase (MCR). The nickel centers in these systems feature sulfur- and nitrogen-rich environments, and in the particular case of lactate racemase, an organometallic nickel pincer motif revealing a Ni-C bond is observed. These bioinorganic systems inspired the development of several nickel pincer scaffolds not only to mimic enzyme active sites and their reactivity but also to further extend low-valent organonickel chemistry. In this Account, we detail our continuing efforts in the chemistry of nickel complexes supported by acridane-based PNP pincer ligands focusing on our long-standing interest in biomimetic small molecule activation. We have employed a series of diphosphinoamide pincer ligands to prepare various nickel(II/I/0) complexes and to study the conversion of C1 chemicals such as CO and CO2 to value-added products. In the transformation of C1 chemicals, the key C-O bond cleavage and C-E bond (E = C, N, O, or S, etc.) formation steps typically require overcoming high activation barriers. Interestingly, enzymatic systems overcome such difficulties for C1 conversion and operate efficiently under ambient conditions with the use of nickel organometallic chemistry. Furthermore, we have extended our efforts to the conversion of NOx anions to NO via the sequential deoxygenation by nickel mediated carbonylation, which was applied to catalytic C-N coupling to produce industrially important organonitrogen compound oximes as a strategy for NOx conversion and utilization (NCU). Notably, the rigidified acriPNP pincer backbone that enforces a planar geometry at nickel was found to be an important factor for diversifying organometallic transformations including (a) homolysis of various σ-bonds mediated by T-shaped nickel(I) metalloradical species, (b) C-H bond activation mediated by a nickel(0) dinitrogen species, (c) selective CO2 reactivity of nickel(0)-CO species, (d) C-C bond formation at low-valent nickel(I or 0)-CO sites with iodoalkanes, and (e) catalytic deoxygenation of NOx anions and subsequent C-N coupling of a nickel-NO species with alkyl halides for oxime production. Broadly, our results highlight the importance of molecular design and the rich chemistry of organonickel species for diverse small molecule transformations.

Bioinformatics in Neonatal/Pediatric Medicine-A Literature Review.

Bioinformatics is a scientific field that uses computer technology to gather, store, analyze, and share biological data and information. DNA sequences of genes or entire genomes, protein amino acid sequences, nucleic acid, and protein-nucleic acid complex structures are examples of traditional bioinformatics data. Moreover, proteomics, the distribution of proteins in cells, interactomics, the patterns of interactions between proteins and nucleic acids, and metabolomics, the types and patterns of small-molecule transformations by the biochemical pathways in cells, are further data streams. Currently, the objectives of bioinformatics are integrative, focusing on how various data combinations might be utilized to comprehend organisms and diseases. Bioinformatic techniques have become popular as novel instruments for examining the fundamental mechanisms behind neonatal diseases. In the first few weeks of newborn life, these methods can be utilized in conjunction with clinical data to identify the most vulnerable neonates and to gain a better understanding of certain mortalities, including respiratory distress, bronchopulmonary dysplasia, sepsis, or inborn errors of metabolism. In the current study, we performed a literature review to summarize the current application of bioinformatics in neonatal medicine. Our aim was to provide evidence that could supply novel insights into the underlying mechanism of neonatal pathophysiology and could be used as an early diagnostic tool in neonatal care.

Leveraging Electron Push-Pull Effect for Catalytic Polymerization and Degradation of a Cyclobutane Monomer System.

Ring-opening polymerization (ROP) offers a striking solution to solve problems encountered in step-growth condensation polymerization, including precise control over molecular weight, molecular weight distribution, and topology. This has inspired our interest in ROP of cycloalkanes with an ultimate goal to rethink polyolefins, which clearly poses a number of challenges. Practicality of ROP of cycloalkanes is actually limited by their low polymerizability and elusive mechanisms which arise from significantly varied ring size and non-polar C-C bonds in monomers. In this work, by using Lewis acid/Brønsted base/C(sp3)-H initiator system previously developed in our laboratory, we focus on cyclobutanes and explore the positional and electronic effects of substituents on the ring, namely electron push-pull effect, in promoting controlled polymerization to afford densely functionalized poly(cyclobutanes), as well as catalytic degradation of obtained polymers for upcycling. More importantly, experiments and DFT calculations unveil considerable population of Lewis-acid-induced thermostabilized 1,4-zwitterions, which distinguish cyclobutanes from cyclopropanes and others. All these findings would shed light on catalytic synthesis and degradation of saturated all-carbon main-chain polymers, as well as small molecule transformations of cyclobutanes.

Leveraging Electron Push‐Pull Effect for Catalytic Polymerization and Degradation of a Cyclobutane Monomer System

AbstractRing‐opening polymerization (ROP) offers a striking solution to solve problems encountered in step‐growth condensation polymerization, including precise control over molecular weight, molecular weight distribution, and topology. This has inspired our interest in ROP of cycloalkanes with an ultimate goal to rethink polyolefins, which clearly poses a number of challenges. Practicality of ROP of cycloalkanes is actually limited by their low polymerizability and elusive mechanisms which arise from significantly varied ring size and non‐polar C−C bonds in monomers. In this work, by using Lewis acid/Brønsted base/C(sp3)‐H initiator system previously developed in our laboratory, we focus on cyclobutanes and explore the positional and electronic effects of substituents on the ring, namely electron push‐pull effect, in promoting controlled polymerization to afford densely functionalized poly(cyclobutanes), as well as catalytic degradation of obtained polymers for upcycling. More importantly, experiments and DFT calculations unveil considerable population of Lewis‐acid‐induced thermostabilized 1,4‐zwitterions, which distinguish cyclobutanes from cyclopropanes and others. All these findings would shed light on catalytic synthesis and degradation of saturated all‐carbon main‐chain polymers, as well as small molecule transformations of cyclobutanes.

Small-Molecule Activation by Low-Coordinated Germanium Compounds

AbstractWe have been interested in the differences between the properties of low-coordinated carbon compounds and their heavier homologues based on elements of group 14, e.g., Si and Ge. Fundamental research on the synthesis and characterization of divalent and multiply bonded compounds of heavier group 14 elements has led to a variety of isolated low-coordinated species of heavier group 14 elements that can replace transition metals in small-molecule transformations. We have focused on low-coordinated germanium compounds with double or triple bonds between germanium atoms, as well as germanium-containing aromatic compounds. Once isolated, the reactivity of these low-coordinated germanium compounds was examined with regard to small-molecule activation. In this account, the reactivity patterns of these compounds will be described.1 Introduction2 1,2-Dibromodigermenes and Bromogermylenes3 Digermynes4 1,2-Digermacyclobutene5 1,3-Digerma-2-silaallene6 Digerma-Aromatic Compounds7 Germanium-Catalyzed Cyclotrimerization of Alkynes8 Summary

Utilising Fourier Transform Voltammetry to Advance the Enzyme Electrochemistry Toolkit

Electron transfer and redox chemistry drives life and Biology can provide inspiration for the design of sustainable fuel catalysts that achieve highly active and selective small molecule transformations. In particular, the Parkin group are interested in hydrogenases,1 biological H2-producing enzymes, and lytic polysaccharide monooxygenases (LPMOs),2, 3 enzymes that breakdown cellulose. We seek to understand how the rate and energetics of electron transfer controls catalysis in such enzymes;4 to do this we collaborate with the Gavaghan and Bond groups to develop more powerful bioelectrochemical methodologies.5 This talk will describe our most recent efforts to integrate sinusoidal voltammetry into our enzyme-electrochemistry toolkit.6, 7 The technique offers advantages in terms of simulation speed, which in turn enables the powerful application of Bayesian statistical analysis to visualise the uncertainty in the modelling approach. However, we still rely on large amplitude Fourier transform voltammetry and direct current methodologies to visualise the Faradaic current and readily define redox reaction parameter bounds.

Heck Migratory Insertion Catalyzed by a Single Pt Atom Site.

Single-atom catalysts (SACs) have generated excitement for their potential to downsize metal particles to the atomic limit with engineerable local environments and improved catalytic reactivities and selectivities. However, successes have been limited to small-molecule transformations with little progress toward targeting complex-building reactions, such as metal-catalyzed cross-coupling. Using a supercritical carbon-dioxide-assisted protocol, we report a heterogeneous single-atom Pt-catalyzed Heck reaction, which provides the first C-C bond-forming migratory insertion on SACs. Our quantum mechanical computations establish the reaction mechanism to involve a novel C-rich coordination site (i.e., PtC4) that demonstrates an unexpected base effect. Notably, the base was found to transiently modulate the coordination environment to allow migratory insertion into an M-C species, a process with a high steric impediment with no previous example on SACs. The studies showcase how SACs can introduce coordination structures that have remained underexplored in catalyst design. These findings offer immense potential for transferring the vast and highly versatile reaction manifold of migratory-insertion-based bond-forming protocols to heterogeneous SACs.

Novel Triangulenes: Computational Investigations of Energy Thresholds for Photocatalytic Water Splitting.

Organic materials with Inverted Singlet-Triplet (INVEST) gaps are interesting for their potential use in photocatalytic small molecule transformations such as the entirely solar-driven water splitting reaction. However, only a few INVEST emitters are thermodynamically able to split water requiring a first singlet excited dark state, S1 , above 1.27 or 1.76 eV, and absorption near solar the maximum, 2.57 eV. These requirements and the INVEST character are key for achieving a long-lived photocatalyst for water splitting. The only known INVEST emitters that conform to these criteria are large triangular boron carbon nitrides with unknown synthesis pathways. Using ADC(2), a quantum-mechanical method, we describe three triangulenes. 3 a is a cyano azacyclopenta[cd]phenalene derivative while 3 b and 3 c are cycl[3.3.3]azine derivatives. 3 b has a previously undescribed disulfide bridge. Overall, 3 a fulfills requirements for photocatalytic four-electron reduction of water while the S1 states of 3 b and 3 c are likely slightly low for the two-electron reduction process. By analyzing impacts of ligands, we find that there are guidelines describing how S1 -S5 energies and oscillator strengths, T1 energies, and ΔES1T1 gaps are affected, requiring deep-learning algorithms for which studies will be presented by us in due time. The impact of ground-state geometries, solvation effects, as well as reduced-cost ADC(2) algorithms on our findings are also discussed.

Enzymatic Bioconjugation: A Perspective from the Pharmaceutical Industry.

Enzymes have firmly established themselves as bespoke catalysts for small molecule transformations in the pharmaceutical industry, from early research and development stages to large-scale production. In principle, their exquisite selectivity and rate acceleration can also be leveraged for modifying macromolecules to form bioconjugates. However, available catalysts face stiff competition from other bioorthogonal chemistries. In this Perspective, we seek to illuminate applications of enzymatic bioconjugation in the face of an expanding palette of new drug modalities. With these applications, we wish to highlight some examples of current successes and pitfalls of using enzymes for bioconjugation along the pipeline and try to illustrate opportunities for further development.

Comparisons of bpy and phen Ligand Backbones in Cr-Mediated (Co-)Electrocatalytic CO2 Reduction

Due to the rise in atmospheric carbon dioxide (CO2) concentrations, there is a need for the development of new strategies to enhance the selectivity and activity of the electrocatalytic conversion of CO2 to value-added products. The incorporation of redox mediators (RMs) as cocatalysts to enhance the transfer of redox equivalents during catalysis has been gaining more attention in recent years across a variety of small molecule transformations. We have shown that using Cr-centered complexes with sulfone-based RMs leads to an enhancement of CO2 reduction electrocatalysis under protic conditions via an inner-sphere mechanism. In these cocatalytic systems, an oxygen atom of the reduced RM binds to the Cr center to form a key intermediate stabilized by pancake bonding between the reduced aromatic components of the catalyst ligand backbone and the RM. This interaction facilitates the transfer of an electron and accesses a more kinetically favorable reaction pathway. Here, we show that expanding the aromatic character of the ligand backbone of the catalyst as well as the RM can cause a greater enhancement of coelectrocatalytic activity. These results suggest that further activity improvements can be achieved by focusing on the kinetic and thermodynamic parameters which control association between the catalyst and RM.

Circular Discovery in Small Molecule and Conjugated Polymer Synthetic Methodology.

Simple and efficient methods are a key consideration for small molecule and polymer syntheses. Direct arylation polymerization (DArP) is of increasing interest for preparing conjugated polymers as an effective approach compared to conventional cross-coupling polymerizations. As DArP sees broader utilization, advancements are needed to access materials with improved properties and different monomer structures and to improve the scalability of conjugated polymer synthesis. Presented herein are considerations for developing new methods of conjugated polymer synthesis from small molecule transformations, exploring how DArP has successfully used this approach, and presenting how emerging polymerization methodologies are developing similarly. While it is common to adapt small molecule methods to polymerizations, we demonstrate the ways in which information gained from studying polymerizations can inform and inspire greater advancements in small molecule transformations. This circular approach to organic synthetic method development underlines the value of collaboration between small molecule and polymer-based synthetic research groups.

Extreme Enhancement of Carbon Hydrogasification via Mechanochemistry.

Carbon hydrogasification is the slowest reaction among all carbon-involved small-molecule transformations. Here, we demonstrate a mechanochemical method that results in both a faster reaction rate and a new synthesis route. The reaction rate was dramatically enhanced by up to 4 orders of magnitude compared to the traditional thermal method. Simultaneously, the reaction exhibited very high selectivity (99.8 % CH4 , versus 80 % under thermal conditions) with a cobalt catalyst. Our study demonstrated that this extreme increase in reaction rate originates from the continuous activation of reactive carbon species via mechanochemistry. The high selectivity is intimately related to the activation at low temperature, at which higher hydrocarbons are difficult to form. This work is expected to advance studies of carbon hydrogasification, and other solid-gas reactions.

Heterogenization of Molecular Electrocatalysts for Small Molecule Transformations

Heterogenization of Molecular Electrocatalysts for Small Molecule Transformations

Nanometals Templated by Tobacco Mosaic Virus Coat Protein with Enhanced Catalytic Activity

Bio-nano hybrid materials feature eco-friendly synthesis, various self-assembly patterns and numerous possibilities of surface functionalization. Owing to these unique advantages, biological scaffolds have been be regarded as green alternatives to fabricate metallic nanomaterials for catalytic applications. In this study, a bulky tobacco mosaic virus coat protein (TMVCP) has been employed as a versatile template to synthesize nanometals (Pd, Pt and Au) in alkaline buffer at room temperature. Protein-functionalized nanoparticles (NPs) with ca. 3 nm in diameter were obtained with uniform size distributions. These materials are green catalytic systems with exceptional performance for small organic molecule transformations in water. Remarkably, while Au NPs showed rapid kinetics in 4-nitrophenol reduction (rate constant with Au NPs: 0.01862 s-1), Pd NPs exhibited superior catalytic activity towards hydrogenation of allyl alcohol (Turnover frequency of Pd NPs: 6382 ± 200 mol product (mol Pd * h)-1) and a set of derivatives. The enhanced catalytic performance is strongly related to the protein ligand. To ascertain the protein structure-function effect on the catalytic performance, an in-depth analysis was performed for the TMVCP-Pd NP system via molecular dynamic (MD) simulations. Our results suggest that due to the moderate interaction between Pd and protein and the steric hindrance of the bulky protein, a large portion of the Pd NP surface remains approachable for the reactant molecules, thus resulting in enhanced reaction rate.

Enhancing the efficiency of semiconducting quantum dot photocatalyzed atom transfer radical polymerization by ligand shell engineering.

Manipulating the ligand shell of semiconducting quantum dots (QDs) has proven to be a promising strategy to enhance their photocatalytic performance for small molecule transformations, such as H2 evolution and CO2 reduction. However, ligand-controlled catalysis for macromolecules, which differ from small molecules in penetrability and charge transfer behavior due to their bulky sizes, still remains undiscovered. Here, we systematically investigate the role of surface ligands in the photocatalytic performance of cadmium selenide (CdSe) QDs in light-induced atom transfer radical polymerization (ATRP) by using thiol-based ligands with various polarities and chain lengths. A highly enhanced polymerization efficiency was observed when 3-mercapto propionic acid (MPA), a short-chain and polar ligand, was used to modify the CdSe QDs' surface, achieving high chain-end fidelity, good temporal control, and a dispersity of 1.18, while also tolerating a wide-range of functional monomers ranging from acrylates to methacrylates and fluorinated monomers. Transient absorption spectroscopy and time-resolved photoluminescence studies reveal interesting mechanistic details of electron and hole transfers from the excited QDs to the initiators and 3-MPA capping ligands, respectively, providing key mechanistic insight of these ligand controlled and QD photocatalyzed ATRP processes. The thiolate ligands were found to serve as an efficient hole acceptor for QDs, which facilitates the formation of a charge-separated state, followed by electron transfer from the conduction band edge to initiators and ultimately suppressing charge recombination within the QD.

Electrochemistry of Ru(edta) complexes relevant to small molecule transformations: Catalytic implications and challenges

Electrochemistry of Ru(edta) complexes (edta4− = ethylenediaminetetraacetate) progressed over a period of several decades, with significant increase in understanding of the electro-catalytic processes involving the substrate coordinated to the metal center. While electrochemistry studies of many Ru(edta) complexes were published in several papers, no attempt has been made to provide a comprehensive and systematic overview of its electrochemical properties, evaluating its application to catalytic electrochemical transformation of small molecules. In this article, results of the electrochemical studies of both mononuclear and binuclear complexes of Ru(edta) are reviewed with regard to electron-transfer reaction mechanism and activity. Their potential to act as redox mediators or catalysts in electrochemical transformations of small molecules and enzymatic reactions, are highlighted. This review aims to contribute to the mechanistic understanding of Ru(edta) complexes in catalysis of such electrochemical transformations.

Activating Water and Hydrogen by Ligand-Modified Uranium and Neptunium Complexes: A Density Functional Theory Study

Organometallic uranium complexes that can activate small molecules are well-known. In contrast, there are no known organometallic trans-uranium species capable of small-molecule transformations. Using density functional theory, we previously showed that changing actinide-ligand bonds from U-O groups to Np-N- (amide/imido) bonds makes redox small-molecule activation more energetically favorable for Np species. Here, we determine how general this ligand-modulation strategy is for affecting small-molecule activation in Np species. We focus on two reactions, one involving redox transformation of the actinide(s) and the other involving no change in the oxidation state of the actinide(s). Specifically, we considered the hydrogen evolution reaction (HER) from H2O by actinide tris-aryloxide species. We also considered H2 capture and hydride transfer by actinide siloxide and silylamide complexes. For the HER, the barriers for Np(III) systems are much higher than those of U(III). The overall reaction energies are also much worse. An-O → An-N substitutions marginally improve the barriers by 1-4 kcal/mol and more substantially improve the reaction energies by 9-15 kcal/mol. For H2 capture and hydride transfer, the reaction energies for the U and Np species are similar. For both actinides, like-for-like An-O → An-N substitutions lead to improved reaction energies. Interestingly, in a recent report, it seemingly appears that U-O (siloxide) → U-N (silylamide) leads to complete shutdown of reactivity for H2 capture and hydride transfer. This observation is reproduced and explained with calculations. The ligand environments of the siloxide and silylamide that were compared are vastly different. The steric environment of the siloxide is conducive for reactivity while the particular silylamide is not. We conclude that small-molecule activation with organometallic neptunium species is achievable with a guided choice of ligands. Additional emphasis should be placed on ligands that can allow for improved transition state barriers.

Organo-f-Complexes for Efficient and Selective Hydroborations

Organo-f-complexes catalyzing small molecule transformations have been a hot topic in the past few years. Compared to other transformations, the hydroboration of C=X (X = C, N, O) unsaturated bonds serves as an important strategy to prepare organoborane derivatives, which are important intermediates in organic synthesis. This review outlines recent advances in organolanthanide and organoactinide complexes promoting the hydroboration of C=X containing substrates. After a brief introduction, three types of hydroboration will be presented: alkene hydroboration, carbonyl hydroboration, and imine and nitrile hydroborations. The catalytic performance, mechanism, and kinetic studies are discussed in detail, aiming to emphasize the catalytic differences between the diverse organo-f-catalysts. Additionally, challenges and future directions of this field are also presented.1 Introduction2 Alkene Hydroboration3 Carbonyl Hydroboration4 Imine and Nitrile Hydroboration5 Conclusions and Outlook

Olefin metathesis catalysts embedded in β-barrel proteins: creating artificial metalloproteins for olefin metathesis.

This review summarizes the recent progress of Grubbs–Hoveyda (GH) type olefin metathesis catalysts incorporated into the robust fold of β-barrel proteins. Anchoring strategies are discussed and challenges and opportunities in this emerging field are shown from simple small-molecule transformations over ring-opening metathesis polymerizations to in vivo olefin metathesis.