Alkyne Fragment Research Articles

Synthesis of Pentaerythritol-Based Branching Reagents for Modification of Proteins and Nucleic Acids by [2+3] Dipolar Cycloaddition Reaction

Alkylation of pentaerythritol symmetrically substituted with propylene glycol with propargyl bromide afforded compounds containing two or three alkyne moieties. Amidophosphite reagents and solid supports were prepared for the introduction of two and three acetylene fragments into oligonucleotides at the 3'- and 5'-positions and inside the chain under conditions of automated solid-phase oligonucleotide synthesis. Based on the trialkynyl derivative, an N-hydroxysuccinimide ester was obtained which can be used to modify biomolecules attacking the amino group. Conjugates obtained can be used for multiple modifications by [3+2] dipolar cycloaddition reaction.

The Sonogashira reaction as a new method for the modification of borated analogues of the green fluorescence protein chromophore

The Sonogashira reaction was used for modifications of borated green fluorescence protein chromophore derivatives, 4-(2-(difluoroboryl)benzylidene)-1H-imidazol-5(4H)-ones, for the development of new fluorescent dyes. The derivatives bearing an acetylene fragment and a difluoroboryl group were obtained in high yields. The modification resulted in a significant bathochromic shift of the absorption and emission maxima and is a promising method for the development of new fluorescent dyes.

Target guided synthesis using DNA nano-templates for selectively assembling a G-quadruplex binding c-MYC inhibitor

The development of small molecules is essential to modulate the cellular functions of biological targets in living system. Target Guided Synthesis (TGS) approaches have been used for the identification of potent small molecules for biological targets. We herein demonstrate an innovative example of TGS using DNA nano-templates that promote Huisgen cycloaddition from an array of azide and alkyne fragments. A G-quadruplex and a control duplex DNA nano-template have been prepared by assembling the DNA structures on gold-coated magnetic nanoparticles. The DNA nano-templates facilitate the regioselective formation of 1,4-substituted triazole products, which are easily isolated by magnetic decantation. The G-quadruplex nano-template can be easily recovered and reused for five reaction cycles. The major triazole product, generated by the G-quadruplex inhibits c-MYC expression by directly targeting the c-MYC promoter G-quadruplex. This work highlights that the nano-TGS approach may serve as a valuable strategy to generate target-selective ligands for drug discovery.

Insights on the Reactivity of Terminal Phosphanido Metal Complexes toward Activated Alkynes from Theoretical Computations.

Herein we present a theoretical study on the reaction of [Re(PPh2) (CO)3(phen)] (phen = 1,10-phenanthroline) and [Re(PPh2) (CO)3(bipy)] (bipy = 2,2'-bipyridine) toward methyl propiolate. In agreement with experimental results for the phen ligand, the coupling of the substituted acetylenic carbon with the nonsubstituted ortho carbon of the phen ligand is the preferred route from both kinetic and thermodynamic viewpoints with a Gibbs energy barrier of 18.8 kcal/mol and an exoergicity of 11.1 kcal/mol. There are other two routes, the insertion of the acetylenic fragment into the P-Re bond and the coupling between the substituted acetylenic carbon and a carbonyl ligand in cis disposition, which are kinetically less favorable than the preferred route (by 2.8 and 1.9 kcal/mol, respectively). Compared with phen, the bipy ligand shows less electrophilic character and also less π electron delocalization due to the absence of the fused ring between the two pyridine rings. As a consequence, the route involving the coupling with a carbonyl ligand starts to be kinetically competitive, whereas the product of the attack to bipy is still the most stable and would be the one mainly obtained after spending enough time to reach thermal equilibrium.

Click reactions in chitosan chemistry

The review provides the first generalized and systematized information on the use of click reactions in chitosan chemistry for the preparation of novel polymers with attractive physicochemical and biological properties. The reactions of copper-catalyzed azide—alkyne cycloaddition and the click reactions of chitosan derivatives occurring in the absence of salts or metal complexes are discussed in detail. The data on the pre-click modification of chito-san (i.e., the introduction of azide function, alkyne fragment, highly dipolarophilic moieties, and thiol group into the polymer) are reviewed. Special attention is given to the application of new chitosan derivatives obtained by click modification.

NHC-Stabilised Acetylene-How Far Can the Analogy Be Pushed?

Experimental studies suggest that the compound (NHCbz )2 C2 H2 can be considered as a complex of a distorted acetylene fragment which is stabilised by benzoannelated N-heterocyclic carbene ligands (NHCbz )→(C2 H2 )←(NHCbz ). A quantum chemical analysis of the electronic structures shows that the description with dative bonds is more favourable than with electron-sharing double bonds (NHCbz )=(C2 H2 )=(NHCbz ).

Theoretical investigation of alignment-dependent intense-field fragmentation of acetylene

We analyze the alignment-dependent dissociative and nondissociative ionization of acetylene, ${\mathrm{C}}_{2}{\mathrm{H}}_{2}$. Numerical models describing the yield of the singly and doubly charged ions $({\mathrm{C}}_{2}{\mathrm{H}}_{2}{}^{+},{\mathrm{C}}_{2}{\mathrm{H}}_{2}{}^{2+})$ and several fragmentation and isomerization channels $({\mathrm{C}}_{2}{\mathrm{H}}^{+}+{\mathrm{H}}^{+},{\mathrm{CH}}^{+}+{\mathrm{CH}}^{+},{\mathrm{CH}}_{2}{}^{+}+{\mathrm{C}}^{+})$ as a function of the relative alignment angle between the laser polarization axis and the molecular axis are presented. We apply and compare two different approaches. The first is based on time-dependent density functional theory. The second is a quasi-single-particle approach using the Dyson orbitals. We find good agreement between the results of both methods. A comparison of our theoretical predictions with experimental data allows us to show that the alignment-dependent yield of most reaction channels is described to high accuracy assuming sequential ionization. However, for some of the fragmentation channels, namely, ${\mathrm{CH}}^{+}+{\mathrm{CH}}^{+}$ and ${\mathrm{C}}_{2}{\mathrm{H}}^{+}+{\mathrm{H}}^{+}$, we find non-negligible influence of recollisional ionization.

Click chemistry methodology in the synthesis of anabasine and cytisine conjugates with isoxazole derivatives

Cytisine and anabasine derivatives containing an acetylenic fragment were used as building blocks in 1,3-dipolar cycloaddition reactions with substituted N-hydroxybenzenecarboximidoyl chlorides, catalyzed by copper(I) salt. The reactions with N-propargylcytisine were not selective, and the products were mixtures of 3,5-disubstituted isoxazoles and small amounts (5–8%) of 3,4-disubstituted isomers. 1,3-Dipolar cycloaddition with N-propargylanabasine afforded 3,5-disubstituted isoxazole derivatives with high regioselectivity.

Reaction pathways and transition states of the C-C and C-H bond cleavage in the aromatic pyrenemolecule - A Density Functional study

The activation and reaction energies of the C-C and C-H bonds cleavage in pyrene molecule are calculated applying the Density Functional Theory and 6-311G Gaussian basis. Different values for the energies result for the different bonds, depending on the location of the bond and the structure of the corresponding transition states. The C-C bond cleavage reactions include H atom migration, in many cases, leading to the formation of CH 2 groups and H-C≡C- acetylenic fragments. The activation energy values of the C-C reactions are greater than 190.00 kcal/mol for all bonds, those for the C-H bonds are greater than 160.00 kcal/mol. The reaction energy values for the C-C bonds range between 56.497 to 191.503 kcal/mol. As for the C-H cleavage reactions the activation energies range from 163.535 to 165.116 kcal/mol, the reaction energies are nearly constant, 117.500kcal/mol. The geometries of the transition states and reaction products are discussed too.

ChemInform Abstract: Target cum Flexibility: Synthesis of Indolo[1,2‐b]isoquinoline Derivatives via Cobalt‐Catalyzed [2 + 2 + 2] Cyclotrimerization.

AbstractThe unnatural 6,11‐dihydroindolo[1,2‐b]isoquinoline tetracyclic core is successfully constructed by a highly modular overall strategy which involves a synchronized step‐by‐step assembly of three different alkyne fragments with a complete freedom to change the substituents on any of desired position.

Ab-initio simulation of the ionization and fragmentation of acetylene by strong femtosecond laser pulses

The electron and nuclear dynamics of acetylene when interacting with strong short laser pulses has been simulated in the framework of real-space Time Dependent Density Functional Theory (TDDFT) and molecular dynamics. The stretching and dissociation of individual bonds are reported, and are shown to depend on the laser field intensity and orientation relative to the laser polarization. The ionization dynamics, including ionization from individual Kohn-Sham orbitals, is also reported. The orbital ionization dynamics are shown to vary with an increase in the intensity of the laser field.

Theoretical study of isomerism of compounds of CN, HCN, and CH2NH molecules with a Ti-doped aluminum cluster

Segments of the potential energy surfaces corresponding to elementary stages of multistep fragmentation of the titled molecules upon their reaction with a Ti-doped aluminum cluster have been calculated by the density functional theory method. There have been localized Al12Ti · L isomers corresponding to absorption, chemisorption, and successive fragmentation of molecules L = CN, HCN, and CH2NH with different ways of insertion of their fragments into the Al12Ti metal cage. Relative energies, structural characteristics, and vibrational frequencies of coordinated and fragment isomers have been calculated, and the barriers separating these isomers have been evaluated. “Nonclassical” isomers with highly coordinated carbon and nitrogen atoms have been localized. The results are compared with the data of previous calculations of the PES of isomers corresponding to fragmentation of acetylene and diimine molecules in related Al12Ti · L complexes with symmetrical ligands L = C2H2 and N2H2.

Synthesis of spiroketal fragment of ossamycin via Prins cyclization

An asymmetric synthesis of spiroketal fragment of an antitumour antibiotic, ossamycin is described. Coupling of aldehyde and alkyne fragments followed by spiroketalization has afforded the spiroketal sub unit of ossamycin. Both the sub targets were constructed via Prins cyclization.

Reactivity of Organogold Compounds with B(C6F5)3: Gold–Boron Transmetalation via σ-B/π-Au Species

The reactions of gold-acetylides with B(C6F5)3 afford alkynyl borate species and cationic π-coordinated gold complexes. The analogous reactions with aryl gold species generate gem-diaurated compounds containing a borate counteranion. These new σ-B/π-Au alkynyl borate complexes can be employed as active catalysts in homogeneous catalysis and represent a new silver-free activation pathway. The new alkynyl borate species are fully characterized, and the alkyne fragments are shown to be bound in a σ-B/π-Au fashion. Upon prolonged heating, these compounds undergo a slow C6F5 group transfer to gold affording LAuC6F5 species.

Electronic Structures of Carbon-Based Kagomé Lattices

A structurally stable two-dimensional carbon allotrope of graphene is studied theoretically based on the first-principles calculations. This allotrope can be formed by inserting acetylene and diacetylene fragments into β-graphyne. The calculations on structure and electronic energy spectra show that the carbon Kagomé lattice is a structurally stable semimetal with the Dirac cones below the Fermi surface, in contrast to the Dirac points at the Fermi surface in intrinsic graphene.

Stereoselective total synthesis of (+)-hyptolide

Stereoselective synthesis of the naturally occurring 6-membered lactone hyptolide 1 is described. The main feature of the synthesis is the utility of the hitherto unexplored alkyne fragment derived from commercially available 3-butyn-1-ol (homopropargylic alcohol).

Observation of the controlled assembly of preclick components in the in situ click chemistry generation of a chitinase inhibitor

The Huisgen cycloaddition of azides and alkynes, accelerated by target biomolecules, termed "in situ click chemistry," has been successfully exploited to discover highly potent enzyme inhibitors. We have previously reported a specific Serratia marcescens chitinase B (SmChiB)-templated syn-triazole inhibitor generated in situ from an azide-bearing inhibitor and an alkyne fragment. Several in situ click chemistry studies have been reported. Although some mechanistic evidence has been obtained, such as X-ray analysis of [protein]-["click ligand"] complexes, indicating that proteins act as both mold and template between unique pairs of azide and alkyne fragments, to date, observations have been based solely on "postclick" structural information. Here, we describe crystal structures of SmChiB complexed with an azide ligand and an O-allyl oxime fragment as a mimic of a click partner, revealing a mechanism for accelerating syn-triazole formation, which allows generation of its own distinct inhibitor. We have also performed density functional theory calculations based on the X-ray structure to explore the acceleration of the Huisgen cycloaddition by SmChiB. The density functional theory calculations reasonably support that SmChiB plays a role by the cage effect during the pretranslation and posttranslation states of selective syn-triazole click formation.

ChemInform Abstract: Facile Synthesis of Electrophilic Vinyl Boranes: Reactions of Alkynyl‐Borates and Diazonium Salts.

AbstractThe title reaction is thought to proceed via the interaction of the electron‐deficient cation derived from the diazonium salt (II) and the alkyne fragment of the alkynylborate (I) generating a transient carbocation adjacent the borate center.

Probing the Binding Site of Abl Tyrosine Kinase Using in Situ Click Chemistry

Modern combinatorial chemistry is used to discover compounds with desired function by an alternative strategy, in which the biological target is directly involved in the choice of ligands assembled from a pool of smaller fragments. Herein, we present the first experimental result where the use of in situ click chemistry has been successfully applied to probe the ligand-binding site of Abl and the ability of this enzyme to form its inhibitor. Docking studies show that Abl is able to allow the in situ click chemistry between specific azide and alkyne fragments by binding to Abl-active sites. This report allows medicinal chemists to use protein-directed in situ click chemistry for exploring the conformational space of a ligand-binding pocket and the ability of the protein to guide its inhibitor. This approach can be a novel, valuable tool to guide drug design synthesis in the field of tyrosine kinases.

Exo/endo Selectivity of the Ring-Closing Enyne Methathesis Catalyzed by Second Generation Ru-Based Catalysts. Influence of Reactant Substituents

The influence of enyne substituents in the product selectivity of the Ring-Closing Enyne Methathesis (RCEYM) catalyzed by the most common mesithyl-containing second-generation Ru-based Grubbs type complexes has been studied by means of density functional theory (DFT, B3LYP-D) calculations. For this, we have computed the energetics of the three proposed mechanism (ene-then-yne; exo-yne-then-ene, and endo-yne-then-ene) of a series of 11 different enynes that share the 1-allyloxyprop-2-yne skeleton. Three different substitutions have been taken into account: the alkyne fragment terminal position, the propargylic carbon, and the internal carbon of the alkene fragment. For the first two substitution positions, models including hypothetical electron-donor and electron-withdrawing substituents have been considered. Present calculations show that nonproductive pathways leading to catalyst deactivation are competitive with the catalytic cycle when nonsubstituted enynes are made to react. Nevertheless, these nonpro...