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The Journal of Physical Chemistry. B Jan 2023The C≡C stretching frequencies of terminal alkynes appear in the "clear" window of vibrational spectra, so they are attractive and increasingly popular as...
The C≡C stretching frequencies of terminal alkynes appear in the "clear" window of vibrational spectra, so they are attractive and increasingly popular as site-specific probes in complicated biological systems like proteins, cells, and tissues. In this work, we collected infrared (IR) absorption and Raman scattering spectra of model compounds, artificial amino acids, and model proteins that contain terminal alkyne groups, and we used our results to draw conclusions about the signal strength and sensitivity to the local environment of both aliphatic and aromatic terminal alkyne C≡C stretching bands. While the IR bands of alkynyl model compounds displayed surprisingly broad solvatochromism, their absorptions were weak enough that alkynes can be ruled out as effective IR probes. The same solvatochromism was observed in model compounds' Raman spectra, and comparisons to published empirical solvent scales (including a linear regression against four meta-aggregated solvent parameters) suggested that the alkyne C≡C stretching frequency mainly reports on local electronic interactions (i.e., short-range electron donor-acceptor interactions) with solvent molecules and neighboring functional groups. The strong solvatochromism observed here for alkyne stretching bands introduces an important consideration for Raman imaging studies based on these signals. Raman signals for alkynes (especially those that are π-conjugated) can be exceptionally strong and should permit alkynyl Raman signals to function as probes at very low concentrations, as compared to other widely used vibrational probe groups like azides and nitriles. We incorporated homopropargyl glycine into a transmembrane helical peptide via peptide synthesis, and we installed -ethynylphenylalanine into the interior of the fatty acid acyl carrier protein using a genetic code expansion technique. The Raman spectra from each of these test systems indicate that alkynyl C≡C bands can act as effective and unique probes of their local biomolecular environments. We provide guidance for the best possible future uses of alkynes as solvatochromic Raman probes, and while empirical explanations of the alkyne solvatochromism are offered, open questions about its physical basis are enunciated.
Topics: Alkynes; Spectrum Analysis, Raman; Solvents
PubMed: 36538691
DOI: 10.1021/acs.jpcb.2c06176 -
International Journal of Molecular... Feb 2022The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is considered to be the most representative ligation process within the context of the "click... (Review)
Review
The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is considered to be the most representative ligation process within the context of the "click chemistry" concept. This CuAAC reaction, which yields compounds containing a 1,2,3-triazole core, has become relevant in the construction of biologically complex systems, bioconjugation strategies, and supramolecular and material sciences. Although many CuAAC reactions are performed under homogenous conditions, heterogenous copper-based catalytic systems are gaining exponential interest, relying on the easy removal, recovery, and reusability of catalytically copper species. The present review covers the most recently developed copper-containing heterogenous solid catalytic systems that use solid inorganic/organic hybrid supports, and which have been used in promoting CuAAC reactions. Due to the demand for 1,2,3-triazoles as non-classical bioisosteres and as framework-based drugs, the CuAAC reaction promoted by solid heterogenous catalysts has greatly improved the recovery and removal of copper species, usually by simple filtration. In so doing, the solving of the toxicity issue regarding copper particles in compounds of biological interest has been achieved. This protocol is also expected to produce a practical chemical process for accessing such compounds on an industrial scale.
Topics: Alkynes; Azides; Catalysis; Click Chemistry; Copper; Cycloaddition Reaction; Triazoles
PubMed: 35216495
DOI: 10.3390/ijms23042383 -
Chemical Communications (Cambridge,... Jan 2011In the last decades, hypervalent iodine reagents have raised from chemical curiosities to mainstream reagents in organic synthesis. The use of benziodoxole-derived... (Review)
Review
In the last decades, hypervalent iodine reagents have raised from chemical curiosities to mainstream reagents in organic synthesis. The use of benziodoxole-derived reagents has been especially successful in oxidation methods, whereas non-cyclic iodinanes have been used both for oxidation and atom-transfer reactions. On the other hand, the exceptional properties of benziodoxole reagents for atom-transfer reactions have only started to attract the attention of the synthetic community more recently. In this review, progress in the use of these compounds for C-X and C-C bond formations will be presented. In particular, recent breakthroughs in trifluoromethylation and alkynylation reactions have been realized since 2006 based on benziodoxole-derived reagents and these results are the main focus of this article.
Topics: Alkynes; Hydrocarbons, Iodinated; Indicators and Reagents; Iodobenzenes; Iodobenzoates; Methylation; Oxidation-Reduction
PubMed: 20820531
DOI: 10.1039/c0cc02265a -
Accounts of Chemical Research Jan 2020Cycloaddition reactions are a hallmark in organic synthesis because they provide an efficient way to construct highly substituted carbo- and heterocycles found in... (Review)
Review
Cycloaddition reactions are a hallmark in organic synthesis because they provide an efficient way to construct highly substituted carbo- and heterocycles found in natural products and pharmaceutical agents. Most cycloadditions occur under thermal or photochemical conditions, but transition-metal complexes can promote reactions that occur beyond these circumstances. Transition-metal complexation with alkynes, alkenes, allenes, or dienes often alters the reactivity of those π-systems and facilitates access to diverse cycloaddition products. This Account describes our efforts toward the design of novel five-carbon synthons for use in rhodium-catalyzed (5 + ) cycloadditions, which include 3-acyloxy-1,4-enynes (ACEs) for (5 + 1) and (5 + 2) cycloadditions and 3-hydroxy-1,4-enynes (HYEs) for (5 + 1) cycloadditions. Furthermore, this Account includes relevant computational information, mechanistic insights, and applications of these cycloadditions in the synthesis of various highly substituted carbo- and heterocycles. The (5 + ) cycloaddition reactions presented herein share the following common mechanistic features: the 1,2-migration of an acyloxy group in propargyl esters or the ionization of a hydroxyl group in propargylic alcohols, oxidative cyclization to form a metallacycle, insertion of the one- or two-carbon component, and reductive elimination to yield the final product. In conjunction with a cationic rhodium catalyst, we used ACEs for the intramolecular (5 + 2) cycloaddition with tethered alkynes, alkenes, and allenes. In some cases, an electron-deficient phosphine ligand improved the reaction yields, especially when the ACE featured an internal alkyne. We also demonstrated that chirality could be efficiently transferred from a relatively simple starting material to a more complex bicyclic product. Products derived from ACEs with tethered alkenes and allenes contained one or more stereocenters, and high diastereoselectivity was achieved in most of these cases. For ACEs tethered to an allene, the reaction preferentially occurred at the internal alkene. We also switched the positions of the alkene and the alkyne in the 1,4-enyne of our original ACE to provide an inverted ACE variant, which produced products with complementary functionalities. After we successfully developed the Rh-catalyzed intramolecular (5 + 2) cycloaddition, we optimized conditions for the intermolecular version, which required a neutral rhodium catalyst and phosphine ligand. When a terminal alkyne was used as the two-carbon component, high regioselectivity was observed. While investigating the effect of esters on the rate of the intermolecular (5 + 2) cycloadditions, we determined that an electron-rich ester significantly accelerated the reaction. Subsequently, we demonstrated that (5 + 1) cycloadditions undergo this rate enhancement as well in the presence of an ester. Aside from ACEs, we synthesized HYEs in four steps from commercially available 2-aminobenzoic acid for use in the (5 + 1) cycloaddition. Mechanistically, HYEs were designed so that the aniline nitrogen could serve as the nucleophile and the -OH could serve as the leaving group. Using HYEs, we developed a novel method to make substituted carbazoles, dibenzofurans, and tricyclic compounds with a cyclohexadienone moiety. Although the occurrence of transition-metal-catalyzed acyloxy migrations has been known for decades, only recently has their synthetic value been realized. We hope our studies that employ readily available 1,4-enynes as the five-carbon components in (5 + ) cycloadditions can inspire the design of new two-component and multicomponent cycloadditions.
Topics: Alkynes; Carbon; Catalysis; Cycloaddition Reaction; Cycloparaffins; Molecular Structure; Rhodium
PubMed: 31820914
DOI: 10.1021/acs.accounts.9b00477 -
Yakugaku Zasshi : Journal of the... 2021The interaction between transition metals and ligands is important for catalytic reactions. The ligands are largely dominated by the covalent X-type (hydride, alkyl and... (Review)
Review
The interaction between transition metals and ligands is important for catalytic reactions. The ligands are largely dominated by the covalent X-type (hydride, alkyl and halogen) and/or dative L-type ligands (e.g., P, N, CO, olefin, etc.). Therefore, the interaction of the Z-type ligands (B, Al and Si, etc.) with transition metals is emerging as a new concept for the reactivity of the metal center. Recently, we developed the synthesis of the gold complex Au(DPB)X (DPB=diphosphine-borane) featuring the Z-type ligand, and their catalytic reaction. The gold catalysts showed a high activity compared to the general catalysts (without Z-ligand) for the various cyclization reactions due to the electron-withdrawing effect of the Z-ligand on the coordinating gold center. In this review, first the structure analysis of the synthesized Au→Z complex is introduced in detail, and second, the catalytic reactions based on the alkyne activation are described.
Topics: Alkynes; Catalysis; Cyclization; Electrons; Gold; Gold Compounds; Ligands; Molecular Structure
PubMed: 33642496
DOI: 10.1248/yakushi.20-00179-1 -
Applied and Environmental Microbiology Apr 2020Ammonia monooxygenase (AMO) is a key nitrogen-transforming enzyme belonging to the same copper-dependent membrane monooxygenase family (CuMMO) as the particulate methane...
Ammonia monooxygenase (AMO) is a key nitrogen-transforming enzyme belonging to the same copper-dependent membrane monooxygenase family (CuMMO) as the particulate methane monooxygenase (pMMO). The AMO from ammonia-oxidizing archaea (AOA) is very divergent from both the AMO of ammonia-oxidizing bacteria (AOB) and the pMMO from methanotrophs, and little is known about the structure or substrate range of the archaeal AMO. This study compares inhibition by C to C linear 1-alkynes of AMO from two phylogenetically distinct strains of AOA, " Nitrosocosmicus franklandus" C13 and " Nitrosotalea sinensis" Nd2, with AMO from and pMMO from (Bath). An increased sensitivity of the archaeal AMO to short-chain-length alkynes (≤C) appeared to be conserved across AOA lineages. Similarities in C to C alkyne inhibition profiles between AMO from AOA and pMMO from suggested that the archaeal AMO has a narrower substrate range than AMO. Inhibition of AMO from " Nitrosocosmicus franklandus" and by the aromatic alkyne phenylacetylene was also investigated. Kinetic data revealed that the mechanisms by which phenylacetylene inhibits " Nitrosocosmicus franklandus" and are different, indicating differences in the AMO active site between AOA and AOB. Phenylacetylene was found to be a specific and irreversible inhibitor of AMO from " Nitrosocosmicus franklandus," and it does not compete with NH for binding at the active site. Archaeal and bacterial ammonia oxidizers (AOA and AOB, respectively) initiate nitrification by oxidizing ammonia to hydroxylamine, a reaction catalyzed by ammonia monooxygenase (AMO). AMO enzyme is difficult to purify in its active form, and its structure and biochemistry remain largely unexplored. The bacterial AMO and the closely related particulate methane monooxygenase (pMMO) have a broad range of hydrocarbon cooxidation substrates. This study provides insights into the AMO of previously unstudied archaeal genera, by comparing the response of the archaeal AMO, a bacterial AMO, and pMMO to inhibition by linear 1-alkynes and the aromatic alkyne, phenylacetylene. Reduced sensitivity to inhibition by larger alkynes suggests that the archaeal AMO has a narrower hydrocarbon substrate range than the bacterial AMO, as previously reported for other genera of AOA. Phenylacetylene inhibited the archaeal and bacterial AMOs at different thresholds and by different mechanisms of inhibition, highlighting structural differences between the two forms of monooxygenase.
Topics: Alkynes; Ammonia; Archaea; Oxidoreductases
PubMed: 32086308
DOI: 10.1128/AEM.02388-19 -
Molecules (Basel, Switzerland) May 2022As one of the abundant and inexpensive metals on the earth, copper has demonstrated broad applications in synthetic chemistry and catalysis. Among these copper-catalyzed... (Review)
Review
As one of the abundant and inexpensive metals on the earth, copper has demonstrated broad applications in synthetic chemistry and catalysis. Among these copper-catalyzed advances, copper carbenes are versatile and reactive intermediates that can mediate a variety of transformations, which have attracted much attention in the past decades. The present review summarizes two different reaction models that take place between a copper carbene intermediate and alkyne species, including the cross-coupling reaction of copper carbene intermediate with terminal alkyne, and the addition of copper carbene intermediate onto the C-C triple bond. This article will cover the profile from 2010 to 2021 by placing emphasis on the detailed catalytic models and highlighting the synthetic applications offered by these practical and mild methods.
Topics: Alkynes; Catalysis; Copper; Methane
PubMed: 35630567
DOI: 10.3390/molecules27103088 -
Biomacromolecules Jun 2023Oligonucleotides are powerful molecules for programming function and assembly. When arrayed on nanoparticle scaffolds in high density, the resulting molecules, spherical...
Oligonucleotides are powerful molecules for programming function and assembly. When arrayed on nanoparticle scaffolds in high density, the resulting molecules, spherical nucleic acids (SNAs), become imbued with unique properties. We used the copper-catalyzed azide-alkyne cycloaddition to graft oligonucleotides on Qβ virus-like particles to see if such structures also gain SNA-like behavior. Copper-binding ligands were shown to promote the click reaction without degrading oligonucleotide substrates. Reactions were first optimized with a small-molecule fluorogenic reporter and were then applied to the more challenging synthesis of polyvalent protein nanoparticle-oligonucleotide conjugates. The resulting particles exhibited the enhanced cellular uptake and protection from nuclease-mediated oligonucleotide cleavage characteristic of SNAs, had similar residence time in the liver relative to unmodified particles, and were somewhat shielded from immune recognition, resulting in nearly 10-fold lower antibody titers relative to unmodified particles. Oligonucleotide-functionalized virus-like particles thus provide an interesting option for protein nanoparticle-mediated delivery of functional molecules.
Topics: Oligonucleotides; Copper; Proteins; Nucleic Acids; Nanoparticles; Azides; Alkynes; Click Chemistry; Cycloaddition Reaction
PubMed: 37257068
DOI: 10.1021/acs.biomac.3c00178 -
Ultrasonics Sonochemistry Jul 2011The search for more efficient and greener synthetic procedures to obtain highly functionalized chemical structures has always found in metal-assisted reactions a... (Review)
Review
The search for more efficient and greener synthetic procedures to obtain highly functionalized chemical structures has always found in metal-assisted reactions a noteworthy strategy. All these reactions fall in the main domain of sonochemistry; in fact few techniques can compete with power ultrasound in so efficiently activating a metal surface, thus enhancing and accelerating its subsequent reaction with an organic substrate. Young researchers will certainly benefit from the rich literature and past experience of several pioneers who have, since the early eighties, laid the foundations of modern sonochemical synthetic protocols. Herein we provide a concise overview that describes how ultrasound acts in such a way as to make it a fundamental tool in improving the classical one-step coupling promoted by zero-valent metal species, usually referred to as Barbier-like reactions. From early hallmarks to recent accomplishments, especially the latest Cu-catalyzed alkyne-azide reaction (the so-called Click reaction), intended to be a universal ligation in chemistry and biology; we highlight the role and crucial effects of sonication on these processes.
Topics: Alcohols; Alkynes; Azides; Catalysis; Click Chemistry; Copper; Ultrasonics
PubMed: 21216171
DOI: 10.1016/j.ultsonch.2010.11.020 -
Chemical Society Reviews Apr 2010Copper-catalyzed azide-alkyne cycloaddition (CuAAC) is a widely utilized, reliable, and straightforward way for making covalent connections between building blocks... (Review)
Review
Copper-catalyzed azide-alkyne cycloaddition (CuAAC) is a widely utilized, reliable, and straightforward way for making covalent connections between building blocks containing various functional groups. It has been used in organic synthesis, medicinal chemistry, surface and polymer chemistry, and bioconjugation applications. Despite the apparent simplicity of the reaction, its mechanism involves multiple reversible steps involving coordination complexes of copper(I) acetylides of varying nuclearity. Understanding and controlling these equilibria is of paramount importance for channeling the reaction into the productive catalytic cycle. This tutorial review examines the history of the development of the CuAAC reaction, its key mechanistic aspects, and highlights the features that make it useful to practitioners in different fields of chemical science.
Topics: Alkynes; Azides; Catalysis; Copper; Cyclization; Iodine; Sulfones
PubMed: 20309487
DOI: 10.1039/b904091a