Pendant Amine Research Articles

A DFT Study: Why Do [Ni(PR2NR′2)2]2+ Complexes Facilitate the Electrocatalytic Oxidation of Formate?

We present a DFT study of the reaction mechanism on electrocatalytic oxidation of formate by a family of [Ni(P(R)2N(R('))2)2](2+) complexes (P(R)2N(R('))2 = 1,5-diR'-3,7-diR derivative of 1,5-diaza-3,7-diphosphacyclooctane, where R and R' are aryl or alkyl groups). [Ni(P(Ph)2N(Me)2)2](2+) complex 1 was used as a model complex to mimic a family of [Ni(P(R)2N(R('))2)2](2+) complexes. Our calculated results show that the decarboxylation step (corresponding to TS3) is the rate-determining step for the electrocatalytic oxidation of formate and that a Ni(II)-H intermediate is involved in the reaction mechanism. The pendant amine plays an important role in the deprotonation of the nickel hydride complex generated in the decarboxylation step. In addition, our study indicates that the choice of external bases is important for removing the proton (H(+)) from the nitrogen-protonated nickel(0) complexes. For the electrocatalytic oxidation of formate using the catalytically inactive [Ni(depe)2](2+) (depe = 1,2-bis(diethylphosphino)ethane) complex, calculations on 1-depe have also been carried out for comparison.

ChemInform Abstract: Enantioselective Total Synthesis of (‐)‐Minovincine in Nine Chemical Steps: An Approach to Ketone Activation in Cascade Catalysis.

ChemInform Abstract: Enantioselective Total Synthesis of (‐)‐Minovincine in Nine Chemical Steps: An Approach to Ketone Activation in Cascade Catalysis.

Ion-Tagged Phosphines as Ligands for Suzuki Coupling of Aryl Halides in a Phosphonium Ionic Liquid

Gramine-based N-substituted phosphines were synthesized and utilized as ligands in Suzuki–Miyaura coupling of aryl bromides and chlorides in the room temperature ionic liquid trihexyltetradecylphosphonium bis(trifluoromethanesulfonyl)imide. Increased yields were achieved with ion-tagged ligands compared to ligands bearing pendant amines, likely due to higher solubility of the former. Cyclohexyl groups on the phosphine moiety generally resulted in higher yields than tert-butyl groups. In addition, a biphasic ionic liquid/water system outperformed catalysis in neat ionic liquid and provided higher yields at lower temperatures.

Proton and Electron Additions to Iron(II) Dinitrogen Complexes Containing Pendant Amines

Protonation of an iron C–H activated complex containing pendant amines in the presence of N2 generated a cis-(H)FeII–N2 complex. Addition of acid protonates the pendant amines. Reduction of the protonated complex results in N2 loss and H2 formation, followed by N2 binding. The origin of H2 formation in this Fe system is compared to proposed mechanisms for H2 loss and N2 coordination in the E4 state of nitrogenase.

Development of Molecular Electrocatalysts for Energy Storage

Molecular electrocatalysts can play an important role in energy storage and utilization reactions needed for intermittent renewable energy sources. This manuscript describes three general themes that our laboratories have found useful in the development of molecular electrocatalysts for reduction of CO2 to CO and for H2 oxidation and production. The first theme involves a conceptual partitioning of catalysts into first, second, and outer coordination spheres. This is illustrated with the design of electrocatalysts for CO2 reduction to CO using first and second coordination spheres and for H2 production catalysts using all three coordination spheres. The second theme focuses on the development of thermodynamic models that can be used to design catalysts to avoid high- and low-energy intermediates. In this research, new approaches to the measurement of thermodynamic hydride donor and acceptor abilities of transition-metal complexes were developed. Combining this information with other thermodynamic information such as pKa values and redox potentials led to more complete thermodynamic descriptions of transition-metal hydride, dihydride, and related species. Relationships extracted from this information were then used to develop models that are powerful tools for predicting and understanding the relative free energies of intermediates in catalytic reactions. The third theme is control of proton movement during electrochemical fuel generation and utilization reactions. This research involves the incorporation of pendant amines in the second coordination sphere that can facilitate H-H bond heterolysis and heteroformation, intra- and intermolecular proton-transfer steps, and coupling of proton- and electron-transfer steps. Studies also indicate an important role for the outer coordination sphere in the delivery of protons to the second coordination sphere. Understanding these proton-transfer reactions and their associated energy barriers is key to the design of faster and more efficient molecular electrocatalysts for energy storage.

Electrochemical oxidation of H2 catalyzed by ruthenium hydride complexes bearing P2N2 ligands with pendant amines as proton relays

A new class of Ru electrocatalysts containing P2N2 diphosphine ligands with pendant amines converts the chemical bond energy of H2 to electricity.

Heterolytic cleavage of H2 by bifunctional manganese(i) complexes: impact of ligand dynamics, electrophilicity, and base positioning

A balance of metal electrophilicity and ligand steric influences is required for facile, reversible H–H heterolytic cleavage in Mn complexes with pendant amines.

Computing Free Energy Landscapes: Application to Ni-based Electrocatalysts with Pendant Amines for H2Production and Oxidation

A general strategy is reported for the computational exploration of catalytic pathways of molecular catalysts. Our results are based on a set of linear free energy relationships derived from extensive electronic structure calculations that permit predicting the thermodynamics of intermediates, with accuracy comparable to experimental data. The approach is exemplified with the catalytic oxidation and production of H2 by [Ni(diphosphine)2]2+ electrocatalysts with pendant amines incorporated in the second coordination sphere of the metal center. The analysis focuses upon prediction of thermodynamic properties including reduction potentials, hydride donor abilities, and pKa values of both the protonated Ni center and the pendant amine. It is shown that all of these chemical properties can be estimated from the knowledge of only the two redox potentials for the Ni(II)/Ni(I) and Ni(I)/Ni(0) couples of the nonprotonated complex, and the pKa of the parent primary aminium ion. These three quantities are easily acc...

Minimal Proton Channel Enables H2 Oxidation and Production with a Water-Soluble Nickel-Based Catalyst

Hydrogenase enzymes use first-row transition metals to interconvert H2 with protons and electrons, reactions that are important for the storage and recovery of energy from intermittent sources such as solar, hydroelectric, and wind. Here we present Ni(P(Cy)2N(Gly)2)2, a water-soluble molecular electrocatalyst with the amino acid glycine built into the diphosphine ligand framework. Proton transfer between the outer coordination sphere carboxylates and the second coordination sphere pendant amines is rapid, as observed by cyclic voltammetry and FTIR spectroscopy, indicating that the carboxylate groups may participate in proton transfer during catalysis. This complex oxidizes H2 (1-33 s(-1)) at low overpotentials (150-365 mV) over a range of pH values (0.1-9.0) and produces H2 under identical solution conditions (>2400 s(-1) at pH 0.5). Enzymes employ proton channels for the controlled movement of protons over long distances-the results presented here demonstrate the effects of a simple two-component proton channel in a synthetic molecular electrocatalyst.

Thermochemical and Mechanistic Studies of Electrocatalytic Hydrogen Production by Cobalt Complexes Containing Pendant Amines

Two cobalt(tetraphosphine) complexes [Co(P(nC-PPh2)2N(Ph)2)(CH3CN)](BF4)2 with a tetradentate phosphine ligand (P(nC-PPh2)2N(Ph)2 = 1,5-diphenyl-3,7-bis((diphenylphosphino)alkyl)-1,5-diaza-3,7-diphosphacyclooctane; alkyl = (CH2)2, n = 2 (L2); (CH2)3, n = 3 (L3)) have been studied for electrocatalytic hydrogen production using 1:1 [(DMF)H](+):DMF. A turnover frequency (TOF) of 980 s(-1) with an overpotential at Ecat/2 of 1210 mV was measured for [Co(II)(L2)(CH3CN)](2+), and a TOF of 980 s(-1) with an overpotential at Ecat/2 of 930 mV was measured for [Co(II)(L3)(CH3CN)](2+). Addition of water increases the TOF of [Co(II)(L2)(CH3CN)](2+) to 18,000 s(-1). The catalytic wave for each of these complexes occurs at the reduction potential of the corresponding HCo(III) complex. Comprehensive thermochemical studies of [Co(II)(L2)(CH3CN)](2+) and [Co(II)(L3)(CH3CN)](2+) and species derived from them by addition/removal of protons/electrons were carried out using values measured experimentally and calculated using density functional theory (DFT). Notably, HCo(I)(L2) and HCo(I)(L3) were found to be remarkably strong hydride donors, with HCo(I)(L2) being a better hydride donor than BH4(-). Mechanistic studies of these catalysts reveal that H2 formation can occur by protonation of a HCo(II) intermediate, and that the pendant amines of these complexes facilitate proton delivery to the cobalt center. The rate-limiting step for catalysis is a net intramolecular isomerization of the protonated pendant amine from the nonproductive exoisomer to the productive endo isomer.

Conformational Dynamics and Proton Relay Positioning in Nickel Catalysts for Hydrogen Production and Oxidation

The [Ni(PR2NR′2)2]2+ complexes (where PR2NR′2 is 1,5-R′-3,7-R-1,5-diaza-3,7-diphosphacyclooctane) are fast electrocatalysts for H2 production and oxidation. Binding of a fifth ligand (CH3CN or BF4–) or chair/boat isomerization has the potential to slow catalysis by blocking the addition of H2 or by incorrectly positioning the pendant amines. We report the structural dynamics of a series of nickel complexes characterized by NMR spectroscopy and theoretical modeling to examine the effects of the fifth ligand for the Ni(II) complexes, including CH3CN, BF4–, Cl–, and H–, as well as the differences in dynamics between the Ni(II) and Ni(0) oxidation states. A fast exchange process was observed for the [Ni(CH3CN)(PR2NR′2)2]2+ complexes, with rates ranging from 104 to 107 s–1 depending on the phosphorus and nitrogen substituents on the PR2NR′2 ligand. This exchange process was identified to occur through a multistep mechanism, which consists of dissociation of the acetonitrile, boat/chair isomerization of each of the four rings (including nitrogen inversion), and reassociation of an acetonitrile on the opposite side of the complex. The rate of the chair/boat inversion was found to be influenced by varying the substituent on the nitrogen atom, but the rate of the overall exchange process is at least an order of magnitude faster than the catalytic rate in acetonitrile, demonstrating that the structural dynamics of the [Ni(CH3CN)(PR2NR′2)2]2+ complexes do not hinder catalysis. Possible catalytic implications of the coordination of a fifth ligand to the Ni(II) complex are discussed.

Polydiacetylene-Based Colorimetric and Fluorescent Chemosensor for the Detection of Carbon Dioxide

We developed a colorimetric and fluorescent turn-on carbon dioxide sensor that relies on a polydiacetylene, PDA-1, functionalized with amines and imidazolium groups. The pendant amines react with CO2 under basic conditions to form carbamoate anions, which partially neutralize the polymer's positive charges, inducing a phase transition. PDA-1 allows for the selective sensing of CO2 with high sensitivity, down to atmospheric concentrations. Naked-eye detection of CO2 is accomplished either in water solutions of PDA-1 or in the solid state with electrospun coatings of PDA-1 nanofibers.

Poly(ethylene oxide)‐graft‐methotrexate Macromolecular Drugs Conjugating via Aminopteridine Ring Exhibit Potent Anticancer Activity

AbstractWater soluble poly(ethylene oxide)‐graft‐methotrexate (PEO‐g‐MTX) conjugates with a robust amide linkage via the amine or carboxylic acid groups of MTX were designed, prepared and investigated for in vitro anti‐tumor effects. MTX was conjugated to multi‐functional PEO containing multiple pendant carboxylic acid (PEO‐g‐COOH) or amine groups (PEO‐g‐NH2) via the carbodiimide chemistry, which afforded PEO‐g‐MTX conjugates with an amide bond to the aminopteridine ring or carboxylic acid groups of MTX (denoted as PEO‐g‐MTX(COOH) and PEO‐g‐MTX(NH2), respectively). Dynamic light scattering (DLS) revealed that all PEO‐g‐MTX conjugates, with MTX contents varying from 4.8 to 19.6 wt%, existed as unimers in phosphate buffer (PB, pH 7.4, 20 mmol·L−1). Interestingly, MTT assays showed that PEO‐g‐MTX(COOH) exhibited potent anti‐tumor activity in HeLa, A549, KB and NIH3T3 cells with cytotoxicity profiles comparable to that of free MTX. In contrast, PEO‐g‐MTX(NH2) revealed diminishing cytostatic effect with IC50 (half maximal inhibitory concentration) ten to hundred times higher than that of PEO‐g‐MTX(COOH). Moreover, PEO‐g‐MTX(COOH) conjugates allowed facile conjugation with targeting ligands. Notably, folate‐decorated PEO‐g‐MTX(COOH) macromolecular drugs showed apparent targetability to folate receptor‐overexpressing KB cells with an IC50 over 12‐fold lower than non‐targeting PEO‐g‐MTX(COOH) control and about 2‐fold lower than free MTX under otherwise the same conditions.

Guanylated Polymethacrylates: A Class of Potent Antimicrobial Polymers with Low Hemolytic Activity

We have synthesized a series of copolymers containing both positively charged (amine, guanidine) and hydrophobic side chains (amphiphilic antimicrobial peptide mimics). To investigate the structure-activity relationships of these polymers, low polydispersity polymethacrylates of varying but uniform molecular weight and composition were synthesized, using a reversible addition-fragmentation chain transfer (RAFT) approach. In a facile second reaction, pendant amine groups were converted to guanidines, allowing for direct comparison of cation structure on activity and toxicity. The guanidine copolymers were much more active against Staphylococcus epidermidis and Candida albicans compared to the amine analogues. Activity against Staphylococcus epidermidis in the presence of fetal bovine serum was only maintained for guanidine copolymers. Selectivity for bacterial over mammalian cells was assessed using hemolytic and hemagglutination toxicity assays. Guanidine copolymers of low to moderate molecular weight and hydrophobicity had high antimicrobial activity with low toxicity. Optimum properties appear to be a balance between charge density, hydrophobic character, and polymer chain length. In conclusion, a suite of guanidine copolymers has been identified that represent a new class of antimicrobial polymers with high potency and low toxicity.

Amine-functionalization of glycidyl methacrylate-containing emulsion-templated porous polymers and immobilization of proteinase K for biocatalysis

Glycidyl methacrylate (GMA) emulsion-templated porous polymers (polyHIPEs) were prepared by thermal and photopolymerisation and derivatised with morpholine, tris(2-aminoethylamine) and a bisamino-PEG homobifunctional molecule. The extent of the functionalization reactions was investigated by a range of qualitative and quantitative techniques (FTIR, CHN analysis, titration, XPS, HR-MAS NMR spectroscopy, ninhydrin assay and Fmoc number determination) and was found to be excellent for small molecule amines (up to 89% conversion) but low for the reaction with PEG (2% conversion). This was ascribed to the high exclusion volume of the PEG chains in solution. Proteinase K (Pro K) was subsequently immobilized covalently onto the GMA polyHIPE material, both directly via reaction with surface epoxy groups and indirectly by activation of the pendent amine groups of PEGylated polyHIPE with glutaraldehyde then reductive amination with the enzyme. The activity of the supported enzymes was determined by a continuous electrochemical assay involving the hydrolysis of N-acetyl-l-tyrosine ethyl ester. The directly immobilized Pro K was found to have an activity of only 3.6 U/g whereas the activity of the enzyme immobilized via the PEG linker was much higher (up to 78 U/g).

Catalytic Activation of H2 under Mild Conditions by an [FeFe]-Hydrogenase Model via an Active μ-Hydride Species

A [FeFe]-hydrogenase model (1) containing a chelating diphosphine ligand with a pendant amine was readily oxidized by Fc(+) (Fc = Cp2Fe) to a Fe(II)Fe(I) complex ([1](+)), which was isolated at room temperature. The structure of [1](+) with a semibridging CO and a vacant apical site was determined by X-ray crystallography. Complex [1](+) catalytically activates H2 at 1 atm at 25 °C in the presence of excess Fc(+) and P(o-tol)3. More interestingly, the catalytic activity of [1](+) for H2 oxidation remains unchanged in the presence of ca. 2% CO. A computational study of the reaction mechanism showed that the most favorable activation free energy involves a rotation of the bridging CO to an apical position followed by activation of H2 with the help of the internal amine to give a bridging hydride intermediate.

Visualization of peroxynitrite-induced changes of labile Zn2+ in the endoplasmic reticulum with benzoresorufin-based fluorescent probes.

Zn(2+) plays essential roles in biology, and the homeostasis of Zn(2+) is tightly regulated in all cells. Subcellular distribution and trafficking of labile Zn(2+), and its inter-relation with reactive nitrogen species, are poorly understood due to the scarcity of appropriate imaging tools. We report a new family of red-emitting fluorescent sensors for labile Zn(2+), ZBR1-3, based on a benzoresorufin platform functionalized with dipicolylamine or picolylamine-derived metal binding groups. In combination, the pendant amines and fluorophore afford an [N3O] binding motif that resembles that of previously reported fluorescein-based sensors of the Zinpyr family, reproducing well their binding capabilities and yielding comparable Kd values in the sub-nanomolar and picomolar ranges. The ZBR sensors display up to 8.4-fold emission fluorescence enhancement upon Zn(2+) binding in the cuvette, with similar responses obtained in live cells using standard wide-field fluorescence microscopy imaging. The new sensors localize spontaneously in the endoplasmic reticulum (ER) of various tested cell lines, allowing for organelle-specific monitoring of zinc levels in live cells. Study of ER zinc levels in neural stem cells treated with a peroxynitrite generator, Sin-1, revealed an immediate decrease in labile Zn(2+) thus providing evidence for a direct connection between ER stress and ER Zn(2+) homeostasis.

A Simple and Versatile Synthetic Strategy to Functional Polypeptides via Vinyl Sulfone-Substituted l-Cysteine N-Carboxyanhydride

Vinyl sulfone-substituted l-cysteine N-carboxyanhydride (VSCys-NCA) monomer was designed and developed to afford a novel and versatile family of vinyl sulfone (VS)-functionalized polypeptides, which further offer a facile access to functional polypeptide-based materials including glycopolypeptides, functional polypeptide coatings, and in situ forming polypeptide hydrogels through Michael-type addition chemistry under mild conditions. VSCys-NCA was obtained in two straightforward steps with a high overall yield of 76%. The copolymerization of γ-benzyl l-glutamate NCA (BLG-NCA), N-benzyloxycarbonyl-l-lysine NCA (ZLL-NCA), or l-leucine NCA (Leu-NCA) with VSCys-NCA using 1,1,1-trimethyl-N-2-propenylsilanamine (TMPS) as an initiator proceeded smoothly in DMF at 40 °C, yielding P(BLG-co-VSCys), P(ZLL-co-VSCys), or P(Leu-co-VSCys) with defined functionalities, controlled molecular weights, and moderate polydispersities (PDI = 1.15–1.50). The acidic deprotection of P(BLG-co-VSCys) and P(ZLL-co-VSCys) furnished water-soluble VS-functionalized poly(l-glutamic acid) (P(Glu-co-VSCys)) and VS-functionalized poly(l-lysine) (P(LL-co-VSCys)), respectively. These VS-functionalized polypeptides were amenable to direct, efficient, and selective postpolymerization modification with varying thiol-containing molecules such as 2-mercaptoethanol, 2-mercaptoethylamine hydrochloride, l-cysteine, and thiolated galactose providing functional polypeptides containing pendant hydroxyl, amine, amino acid, and saccharide, respectively. The contact angle and fluorescence measurements indicated that polymer coatings based on P(Leu-co-VSCys) allowed direct functionalization with thiol-containing molecules under aqueous conditions. Moreover, hydrogels formed in situ upon mixing aqueous solutions of P(Glu-co-VSCys) and thiolated glycol chitosan at 37 °C. These vinyl sulfone-functionalized polypeptides have opened a new avenue to a broad range of advanced polypeptide-based materials.

Evaluation of the Role of Water in the H2 Bond Formation by Ni(II)-Based Electrocatalysts

We investigate the role of water in the H-H bond formation by a family of nickel molecular catalysts that exhibit high rates for H2 production in acetonitrile solvent. A key feature leading to the high reactivity is the Lewis acidity of the Ni(II) center and pendant amines in the diphosphine ligand that function as Lewis bases, facilitating H-H bond formation or cleavage. Significant increases in the rate of H2 production have been reported in the presence of added water. Our calculations show that molecular water can displace an acetonitrile solvent molecule in the first solvation shell of the metal. One or two water molecules can also participate in shuttling a proton that can combine with a metal hydride to form the H-H bond. However the participation of the water molecules does not lower the barrier to H-H bond formation. Thus these calculations suggest that the rate increase due to water in these electrocatalysts is not associated with the elementary step of H-H bond formation or cleavage but rather with the proton delivery steps. We attribute the higher barrier in the H-H bond formation in the presence of water to a decrease in direct interaction between the protic and hydridic hydrogen atoms forced by the water molecules.

Rapid, Reversible Heterolytic Cleavage of Bound H2

Heterolytic cleavage of dihydrogen into a proton and a hydride ion is a fundamentally important step in many reactions, including the oxidation of hydrogen by hydrogenase enzymes and ionic hydrogenation of organic compounds. We report the facile, reversible heterolytic cleavage of H2 in a manganese complex bearing a pendant amine, leading to the formation of a manganese hydride and a protonated amine that undergo H(+)/H(-) exchange at an estimated rate of >10(7) s(-1) at 25 °C.