Alkyne Fragment Research Articles

The Acetylene Bridge in Intramolecular Singlet Fission: A Boon or A Nuisance?

Various analogues of the alkylsilylacetylene group are frequently used as auxiliary groups to enhance the solubility and stability of the acene dimer core, widely used as platforms to investigate intramolecular singlet fission (iSF) mechanisms. However, while in the 2,2'-linked dimers they are primarily auxiliary groups, these are essential fragments of the bridging units in 6,6'/5,5'-linked dimers, the two preferred choices for dimerization. The starkly different iSF dynamics observed in the two variants raise the question of what role the acetylene bridges play. Here, we systematically designed a set of (oligo-)para-phenylene bridged 2,2'-linked pentacene dimers with an additional acetylene fragment in the bridging unit to mimic the structure of 6,6'-linked dimers. Contrasting the results with previously reported analogous 2,2'-linked and 6,6'-linked pentacene dimers reveals that the acetylene bridges contribute to significant conformational freedom. This effect provides a mechanism to promote spin evolution within the triplet pair to achieve free triplets but also offers new parasitic pathways for triplet-pair recombination, revealing that this structural motif can be both a boon and a nuisance. Additionally, our analysis reveals that these bridges directly modify the electronic states, highlighting significant pitfalls of the standard chromophore-bridge-chromophore framework used to design and interpret photophysics of iSF materials.

The Acetylene Bridge in Intramolecular Singlet Fission: A Boon or A Nuisance?

Various analogues of the alkylsilylacetylene group are frequently used as auxiliary groups to enhance the solubility and stability of the acene dimer core, widely used as platforms to investigate intramolecular singlet fission (iSF) mechanisms. However, while in the 2,2’‐linked dimers they are primarily auxiliary groups, these are essential fragments of the bridging units in 6,6’/5,5’‐linked dimers, the two preferred choices for dimerization. The starkly different iSF dynamics observed in the two variants raise the question of what role the acetylene bridges play. Here, we systematically designed a set of (oligo‐)para‐phenylene bridged 2,2’‐linked pentacene dimers with an additional acetylene fragment in the bridging unit to mimic the structure of 6,6’‐linked dimers. Contrasting the results with previously reported analogous 2,2’‐linked and 6,6’‐linked pentacene dimers reveals that the acetylene bridges contribute to significant conformational freedom. This effect provides a mechanism to promote spin evolution within the triplet pair to achieve free triplets but also offers new parasitic pathways for triplet‐pair recombination, revealing that this structural motif can be both a boon and a nuisance. Additionally, our analysis reveals that these bridges directly modify the electronic states, highlighting significant pitfalls of the standard chromophore‐bridge‐chromophore framework used to design and interpret photophysics of iSF materials.

Rh-Catalyzed C-H Alkynylation of Indole Derivatives with Silver(I)-Controlled Regiodivergence.

We have disclosed silver(I)-induced switching of regioselectivity in rhodium-catalyzed C-H alkynylation of indole derivatives with the help of a pivaloyl directing group by tuning C-H metalation modes. The judicious choice of AgOAc, Ag2O, and Ag2CO3 affords an array of C2-alkynylated indoles, C4-alkynylated indoles, and C2,C4-dialkynylated indoles, respectively. The synthetic utility of the alkyne fragment is demonstrated by derivatization into valuable indole-based compounds.

One-Stage Pathway from Hollongdione to C17-Alkyne and Vinyl Chloride Following Mannich Bases and Carboxylic Acid.

Hollongdione is the first recorded example of the occurrence of a dammarane hexanor-triterpene in nature possessing antiviral and cytotoxic activity. Its simple one-stage transformation into compounds with terminal alkyne and vinyl chloride fragments via the interaction with phosphorus halides is reported. The copper(I)-catalyzed Mannich reaction of 3-oxo-22,23,24,25,26,27-hexanor-dammar-20(21)-in 3 led to a series of aminomethylated products, while 17-carboxylic acid was obtained by ozone oxidation of 3-oxo-22,23,24,25,26,27-hexanor-dammar-20-chloro-20(21)-en 4; the following direct amidation of the latter has been developed. The structures of all new molecules were established by spectroscopic studies that included 2D NMR correlation methods; the molecular structures of compounds 2-5 were determined by X-ray analysis.

Exploring the Impact of Elements on the Reactivity of a Straightforward Procedure for Generating Vinyl-Carbazole Derivatives via a Frustrated Lewis Pair Mechanism.

The effect of chemical element on the reactivity for carbazolation reaction of phenylacetylene utilizing G13(C6F5)3 (Lewis acid) and G15-carbazole (Lewis base) was theoretically investigated using density functional theory (M06-2X-D3/def2-TZVP), where G13 represents Group 13 elements and G15 represents Group 15 elements. Through activation strain model (ASM) analysis, it is apparent that the reactivity of the entire carbazolation reaction is chiefly governed by the structural strain energy of the alkyne fragment. In other words, if G13(C6F5)3 or G15-carbazole features an atomic radius that is either too small (e.g., B atom) or too large (e.g., Tl or Bi atom), it results in inadequate orbital overlap between the reactants due to the impact of steric effects. This, in turn, results in an elevation of the activation energy for such reactions, thereby impeding the alkyne from undergoing the carbazole catalytic reaction. In light of the above analyses, our theoretical findings suggest that, except for Tl(C6F5)3, the other four Lewis acid catalysts (B(C6F5)3, Al(C6F5)3, Ga((C6F5)3, and In((C6F5)3) demonstrate effectiveness in catalyzing the carbazolation reaction of alkyne alongside with N-carbazole. Additionally, it is anticipated that, among the five categories of G15-carbazole molecules studied, only N-carbazole can participate in the carbazolation reaction with alkyne catalyzed by B(C6F5)3, considering both kinetic and thermodynamic factors at room temperature. Our theoretical investigations, as outlined in this study, indicate that the carbazolation reaction of the alkyne, catalyzed by G13(C6F5)3 and G15-carbazole, follows Hammond's postulate. To put it more plainly, when the transition state of the chemical reaction occurs earlier, it results in a decrease in activation energy.

Combating multidrug-resistance in S. pneumoniae: a G-quadruplex binding inhibitor of efflux pump and its bio-orthogonal assembly.

Antibiotic resistance poses a significant global health threat, necessitating innovative strategies to combat multidrug-resistant bacterial infections. Streptococcus pneumoniae, a pathogen responsible for various infections, harbors highly conserved DNA quadruplexes in genes linked to its pathogenesis. In this study, we introduce a novel approach to counter antibiotic resistance by stabilizing G-quadruplex structures within the open reading frames of key resistance-associated genes (pmrA, recD and hsdS). We synthesized An4, a bis-anthracene derivative, using Cu(I)-catalyzed azide-alkyne cycloaddition, which exhibited remarkable binding and stabilization of the G-quadruplex in the pmrA gene responsible for drug efflux. An4 effectively permeated multidrug-resistant S. pneumoniae strains, leading to a substantial 12.5-fold reduction in ciprofloxacin resistance. Furthermore, An4 downregulated pmrA gene expression, enhancing drug retention within bacterial cells. Remarkably, the pmrA G-quadruplex cloned into the pET28a(+) plasmid transformed into Escherichia coli BL21 cells can template Cu-free bio-orthogonal synthesis of An4 from its corresponding alkyne and azide fragments. This study presents a pioneering strategy to combat antibiotic resistance by genetically reducing drug efflux pump expression through G-quadruplex stabilization, offering promising avenues for addressing antibiotic resistance.

Synthesis and Biophysical Properties of Triazole-Incorporated PMOs (TzPMOs): A Convergent, Click Ligation Approach.

The synthesis of phosphorodiamidate morpholino oligonucleotides (PMOs) incorporating single or double triazole rings in the backbone has been achieved via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The synthetic approach implemented is fundamentally convergent, involving the ligation of a 5'-azide PMO fragment to a 3'-alkyne fragment both in solution and on solid support. To access the 3'-alkyne PMO fragment, we synthesized 3'-N-propargyl chlorophosphoramidate morpholino monomers for all four nucleobases. The resulting triazole-incorporated PMOs (TzPMOs) have exhibited comparable or improved binding affinity toward complementary deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) strands compared to its regular analogues. Finally, a full-length TzPMO was designed to target the Nanog gene, demonstrating almost identical hybridization properties when compared to its regular version. Circular dichroism studies revealed a B-type helical conformation for the duplexes formed by TzPMOs.

Ca(II) and Yb(II) complexes featuring M(C≡C)4 structural motif: enforced proximity or genuine η2 -bonding?

Bis(carbazolide) complexes M[3,6-tBu2 -1,8-(RC≡C)2 Carb]2 (THF)n (R=SiMe3 , n=0, M=Ca, Yb; R=Ph, n=1, M=Ca, Yb; n=0, M=Yb) were synthesized through transamination reaction of M[N(SiMe3 )2 ]2 (THF)2 with two molar equivalents of carbazoles. The complexes feature M(η2 -C≡C)4 structural motif composed of M(II) ions encapsulated by four acetylene fragments due to atypical for alkaline- and rare-earth metals η2 -interactions with triple C≡C bond. This interaction is evidenced experimentally by X-ray diffraction, Raman spectroscopy in the solid state and by NMR-spectroscopy in the solution. According to QTAIM analysis there are 4 bond critical points (3;-1) between the metal atom and each of the triple bonds, which are connected by a strongly curved, almost T-shaped bond pathway.

The scandium organometallic behavior. Design of a chamber of reaction to trap CO2

Scandium has shown it can interact with aromatic rings in η5 or η1 fashion, in this work both possibilities are studied by means DFT methods and the properties of the resultant structures are exploited for the design of a reaction chamber. Interestingly, according to our first results analyzed, the origin of this chamber is an organometallic complex which bears two η4-Cp and one η1-benzene unities. From the frontier molecular orbitals and AIM analysis we inferred that this last bond can be described as a σ dative bond C-Sc. Whit base on AIM and NBO analysis, the association of six of these species gives place to a complex containing two cavities, where an electron density coming from the acetylene fragments in the wall of the chamber can conform a reactive zone, that due to its properties is studied with the aim to trap CO2 and H2 in order to produce formic acid. Thermodynamic and kinetic results predict that this reaction can occur with an activation energy of 24.79 Kcal/mol and energy of reaction of −7.05 kcal/mol.

Neutral Three Membered 2π Aromatic Beryllacycle having σ hole

AbstractThe electronic structure, bonding, and reactivity of three‐membered cyclic beryllium compounds BeR (R=C2H2 (1), C2(CH3)2 (2)) were studied at the M06/def2‐TZVPP//BP86/def2‐TZVPP level of theory. The molecular orbital analysis shows that BeR is a 2π electron aromatic system with a σ‐hole on the beryllium atom. EDA‐NOCV analysis has been carried out with Be and R in their different electronic state as fragments at the BP86/TZ2P level of theory. The results reveal the preference for three bonding situations, (a) charge‐separated interaction where anionic acetylenic fragment R− forms one electron sharing and one donor‐acceptor σ‐interaction and one donor‐acceptor π interaction with Be+ having 2s02px02py12pz0 electronic configuration (A), (b) charge separated interaction where anionic acetylenic fragment R− forms one electron sharing and one donor‐acceptor σ‐interaction and one donor‐acceptor π interaction with Be+ having 2s12px02py02pz0 electronic configuration (B), and (c) neutral acetylenic fragment forms two electron sharing σ bonds and one donor‐acceptor π bond with beryllium having 2s12px02py12pz0 electronic configuration (C). BeR compounds show high proton affinity and hydride affinity. The reactivity was studied in detail with different ligands CO, NHC, cAAC, and PMe3. The reaction energy for the formation of adducts is exothermic and follows the order of cAAC>NHC>PMe3>CO.

A novel HBI-based ratiometric fluorescent probe for rapid detection of trifluoroborate.

A 2-(2'-hydroxyphenyl)benzimidazole (HBI)-based ratiometric fluorescent probe, known as BTEP, was synthesized using 5-bromosalicylaldehyde as the raw material via Sonogashira coupling and condensation reaction. This probe was designed for rapid detection of boron trifluoride solutions and gases. The N and O coordination atoms in the probe undergo a boron difluoride addition with BF3, which affects the process of excited state intramolecular proton transfer (ESIPT) leading to a blue shift of fluorescence emission. Obvious changes in the fluorescence signal can be observed within 60 seconds. The introduction of an acetylene trimethylsilane fragment increases the conjugate plane and is beneficial to improving the selectivity of the probe. The I408/I479 fluorescence ratio of the probe displays a linear relationship with the concentration of BF3 in the range of 5-50 μM, with a detection of limit as low as 69.5 nM. Furthermore, the probe demonstrates specific and selective recognition of BF3 among eight common interference substances. Test strips prepared using BTEP have the capability of real-time naked-eye detection of trace BF3 gas.

Expanding the Toolbox of Target Directed Bio-Orthogonal Synthesis: In Situ Direct Macrocyclization by DNA Templates.

Herein, we demonstrate for the first time that noncanonical DNA can direct macrocyclization-like challenging reactions to synthesize gene modulators. The planar G-quartets present in DNA G-quadruplexes (G4s) provide a size complementary reaction platform for the bio-orthogonal macrocyclization of bifunctional azide and alkyne fragments over oligo- and polymerization. G4s immobilized on gold-coated magnetic nanoparticles have been used as target templates to enable easy identification of a selective peptidomimetic macrocycle. Structurally similar macrocycles have been synthesized to understand their functional role in the modulation of gene function. The innate fluorescence of the in situ formed macrocycle has been utilized to monitor its cellular localization using a G4 antibody and its in cell formation from the corresponding azide and alkyne fragments. The successful execution of in situ macrocyclization in vitro and in cells would open up a new dimension for target-directed therapeutic applications.

Expanding the Toolbox of Target Directed Bio‐Orthogonal Synthesis: In Situ Direct Macrocyclization by DNA Templates

AbstractHerein, we demonstrate for the first time that noncanonical DNA can direct macrocyclization‐like challenging reactions to synthesize gene modulators. The planar G‐quartets present in DNA G‐quadruplexes (G4s) provide a size complementary reaction platform for the bio‐orthogonal macrocyclization of bifunctional azide and alkyne fragments over oligo‐ and polymerization. G4s immobilized on gold‐coated magnetic nanoparticles have been used as target templates to enable easy identification of a selective peptidomimetic macrocycle. Structurally similar macrocycles have been synthesized to understand their functional role in the modulation of gene function. The innate fluorescence of the in situ formed macrocycle has been utilized to monitor its cellular localization using a G4 antibody and its in cell formation from the corresponding azide and alkyne fragments. The successful execution of in situ macrocyclization in vitro and in cells would open up a new dimension for target‐directed therapeutic applications.

Voltammetric and Spectroscopic Investigation of Electrogenerated Oligo-Thiophenes: Effect of Substituents on the Energy-Gap Value

Oligothiophenes are especially appealing due to their promising applications in different fields, including photosensitive devices. In this context, anchoring a selected substituent on the main structure of the starting material can induce changes in redox and spectroscopic features, according to the nature of the substituent and its position on central or terminal rings. Here, an electrochemical and spectroscopic comparison between 2,2′:5′,2″-terthiophene (2), 5-Br-terthiophene (3) and 5-ethynyl-terthiophene (5-ET) is reported, aimed at elucidating the effect of the nature of the substituent on the energy gap value of the terthiophene skeleton. Furthermore, in order to understand the influence of a selected substituent in varying its position on the terthiophene backbone, 5-ET is compared to the previously described 3′-ethynyl-terthiophene (3′-ET). Experimental results are confirmed by DFT calculations, showing a higher extension of the electron density in 5-ET compared to 2 and 3, as well as to 3′-ET. In addition, as a consequence of the presence of the unsaturated fragment on the C-5-position, the energy gap value of poly-5-ET (the electrogenerated film from 5-ET) appears significantly lower than poly-2 and poly-3. Finally, the higher conjugation effect of a terminal acetylene fragment compared to a central one is confirmed by the energy gap values of poly-5-ET and poly-3′-ET.

The Synthesis of Novel 7-(Substituted benzyl)-4,5-dihydro[1,2,3]triazolo[1,5-a]pyrazin-6(7H)-ones via Tandem Ugi–Huisgen Reactions

AbstractA convenient method for the synthesis of 2-azido-3-arylpropanoic acids via the Meerwein halogenoarylation reaction of acrylic acid esters with diazonium salts, subsequent nucleophilic substitution of the halogen by an azide, and saponification is developed. The newly formed 2-azido-3-arylpropanoic acids react under the conditions of non-catalytic four-component Ugi reactions, leading to the formation of α-azidoamides in good yields. The use of propargylamine as the amine component allows the formation of Ugi adducts with azide and acetylene motifs ready for intramolecular 1,3-dipolar Huisgen cycloaddition to give the [1,2,3]triazolo[1,5-a]pyrazine annulated system. The Ugi reaction is found to give 2-azido-3-aryl-N-(2-oxo-1,2-disubstituted ethyl)-N-(prop-2-yn-1-yl)propanamides at room temperature without azide–alkyne cycloaddition. These dipeptides are converted into 4,5-dihydro[1,2,3]triazolo[1,5-a]pyrazin-6(7H)-ones in near quantitative yields by heating in toluene. However, when the Ugi reaction is carried out by heating, it results in a one-pot Ugi–Huisgen tandem reaction leading to 4,5-dihydro[1,2,3]triazolo[1,5-a]pyrazin-6(7H)-ones in excellent yields. Moreover, the possibility of the incorporation of a bromovinyl fragment (the synthetic equivalent of an acetylene fragment) via the aldehyde component of the Ugi reaction is demonstrated in an alternative preparation of the [1,2,3]triazolo[1,5-a]pyrazine system.

On the mechanism of the Au(I)‐mediated addition of alkynes to anthranils to furnish 7‐acylindoles

Indole is a very common structural motif in alkaloids with a remarkable history in pharma industry. In the continuous search for more direct and efficient access to these valuable structures, a new and rather elegant approach was found by Jin and coworkers, which involved a gold(I)-mediated addition of alkynes onto anthralins. This approach selectively furnishes 7-acylindoles in a rather expeditious way, and it has been shown to be compatible with a large range of decorated reactants, both at the alkyne side and at the anthralin side. We studied the mechanism of this reaction with a set of different alkynes, including disubstituted ones, to establish similarities and differences between them and to aid in the elucidation of key steps in the reaction pathway. The observed regioselectivity seems to be connected to the irreversible formation of a key α-imino gold carbene intermediate, common to all reaction profiles, through the initial regioselective nucleophilic attack of the anthranil N atom onto the alkyne fragment.

On the formation chemistry of brominated polycyclic aromatic hydrocarbons (BrPAHs)

Brominated polycyclic aromatic hydrocarbons (BrPAHs) have been consistently detected in various environmental matrices, and measured at alarming rates in stack emissions. However, formation mechanisms and bromination patterns of BrPAHs remain unclear. This contribution constructs detailed mechanistic pathways for the synthesis of selected BrPAHs (namely bromine-bearing naphthalene, acenaphthylene, anthracene, and phenanthrene). Mapped-out pathways follow the Bittner-Howard's route in the hydrogen abstraction acetylene addition (HACA) mechanism, in which a second C2HBr molecule is added to the first one. Constructed kinetic model portrays temperature-dependent profiles of major and minor species. Direct loss of an H atom from the acetylenic fragment appears to be more important at elevated temperatures, when compared with further addition of C2HBr cuts or ring-cyclization reactions. The occurrence of closed-shell Diels-Alder pathway should be inhibited owing to sizable enthalpic barriers. Fukui Indices for electrophilic substitutions (f−1) establish bromination’ s pattern of selected BrPAHs. The diradical character of BrPAHs coupled with electron-deficient C(Br) sites, render BrPAHs as potent precursors for the formation of environmentally persistent free radicals (EPFRs). Findings reported herein shall be useful in comprehending the formation chemistry of BrPAHs, a less-investigated category of toxicants in thermal systems.

Stereoselective Synthesis of the C19–C39 Fragment of Bastimolide A

AbstractThis paper describes the synthesis of the C19–C39 fragment of the antimalarial natural product bastimolide A via addition of a functionalized C19–C26 alkyne fragment to a C27–C39 aldehyde fragment. Opening of a terminal epoxide and Noyori asymmetric reduction were used as key steps in the synthesis.

Correlation between bonding, philicity and substituent effects in cyclopropenylidenes

The electronic structure and bonding of cyclopropenylidenes with different substituents at the olefinic position viz., –H (1), electron-withdrawing groups (–CHO (2) and –COOH (3)) and electron-donating groups (–N(CH3)2 (4) and –N(iPr)2 (5)), have been explored at the M06/def2-TZVPP//BP86/def2-TZVPP level of theory. The ground state of cyclopropenylidenes 1 – 5 is a singlet 2π-aromatic system with a considerable singlet–triplet energy gap. The geometrical and electronic structure analyses indicate that the nucleophilicity of the carbene lone pair increases when substituents change from electron-withdrawing to electron-donating groups. The energy decomposition analysis combined with natural orbitals for chemical valence (EDA-NOCV) analysis indicates that the bonding interaction between the carbene carbon and the –C2R2 fragment in the parent cyclopropenylidene (1) can be best represented by two electron-sharing σ-bonds and a donor–acceptor π-bond from –C2R2 fragment to the carbene carbon. The pz-orbital on the carbene carbon atom is susceptible to nucleophilic attack if the incoming nucleophile is stronger than the π -MO of the acetylenic fragment. When the substituents change to electron-withdrawing groups, −CHO (2) and –COOH (3), the σ-bonds turn into donor–acceptor interactions. The py and pz-orbitals on the carbene carbon atom are accepting electrons from the acetylenic fragment. Hence these orbitals are susceptible to nucleophilic attack. On the other hand, when the substituents change to electron-donating groups, −N(CH3)2 (4) and −N(iPr)2 (5), the best bonding situation changes into one electron-sharing σ-bond and π-bond along with one donor–acceptor σ-bond from −C2R2 fragment to the carbene carbon. The py-orbital is accepting electrons from the acetylenic fragment. Hence, py-orbital is susceptible to nucleophilic attack, which in turn leads to Ccarbene–C bond cleavage. These bonding descriptions are in agreement with the experimental isolation of several derivatives of cyclopropenylidene.

P‐12.8: Synthesis Method for Obtaining Arylacetylenecarboxylic Acids ‐ Synthons for Liquid Crystalline Compounds

One of the methods for achieving high values of refractive indices (n│ / n┴) in the nematic phase is the use of unsaturated hydrocarbon fragments C = C C≡C in 1,4‐polyphenylene systems. Tolanic and terminal acetylene fragments are widely used in liquid crystal molecules, which are practically used in liquid crystal compositions. Arylacetylenecarboxylic acids are useful building blocks for tolanic structure synthesis. In this article we present an alternative method of synthesis arylacetylenecarboxylic acids in a two‐phase system using PEG as a catalyst.