Alkyne Complexes Research Articles

Group 4 Metallocene Complexes and Cyanopyridines: Coordination or Coupling to Metallacycles

AbstractThe reactions of the group 4 metallocene alkyne complexes Cp*2M(η2‐Me3SiC2SiMe3) (M = Ti, Zr) with different cyanopyridines were investigated. For the zirconium compound, the unstable products Cp*2Zr(η2‐Me3SiC2SiMe3)(N≡C‐py) were first formed by the end‐on coordination of the substrate. Subsequent reaction with a second equivalent resulted in the elimination of the alkyne and in the formation of 1‐zircona‐2,5‐diazacyclopenta‐2,4‐dienes. By applying (2‐bromo)‐5‐cyanopyridine, Cp*2ZrBr2 was also isolated. Nitrile–nitrile C–C couplings of the cyanopyridines to five‐membered metallacycles also occurred for the titanium complexes, but without the generation of side products. By using 2,6‐dicyanopyridine, this reaction resulted in the formation of a tetranuclear complex. The structures, stability, and reactivity of the complexes were analysed and rationalised on the basis of DFT calculations.

Combined Interactions of Plant Homeodomain and Chromodomain Regulate NuA4 Activity at DNA Double-Strand Breaks.

DNA double-strand breaks (DSBs) represent one of the most threatening lesions to the integrity of genomes. In yeast Saccharomyces cerevisiae, NuA4, a histone acetylation complex, is recruited to DSBs, wherein it acetylates histones H2A and H4, presumably relaxing the chromatin and allowing access to repair proteins. Two subunits of NuA4, Yng2 and Eaf3, can interact in vitro with methylated H3K4 and H3K36 via their plant homeodomain (PHD) and chromodomain. However, the roles of the two domains and how they interact in a combinatorial fashion are still poorly characterized. In this study, we generated mutations in the PHD and chromodomain that disrupt their interaction with methylated H3K4 and H3K36. We demonstrate that the combined mutations in both the PHD and chromodomain impair the NuA4 recruitment, reduce H4K12 acetylation at the DSB site, and confer sensitivity to bleomycin that induces DSBs. In addition, the double mutant cells are defective in DSB repair as judged by Southern blot and exhibit prolonged activation of phospho-S129 of H2A. Cells harboring the H3K4R, H3K4R, K36R, or set1Δ set2Δ mutant that disrupts H3K4 and H3K36 methylation also show very similar phenotypes to the PHD and chromodomain double mutant. Our results suggest that multivalent interactions between the PHD, chromodomain, and methylated H3K4 and H3K36 act in a combinatorial manner to recruit NuA4 and regulate the NuA4 activity at the DSB site.

NAA10 mutation causing a novel intellectual disability syndrome with Long QT due to N-terminal acetyltransferase impairment.

We report two brothers from a non-consanguineous Irish family presenting with a novel syndrome characterised by intellectual disability, facial dysmorphism, scoliosis and long QT. Their mother has a milder phenotype including long QT. X-linked inheritance was suspected. Whole exome sequencing identified a novel missense variant (c.128 A > C; p.Tyr43Ser) in NAA10 (X chromosome) as the cause of the family’s disorder. Sanger sequencing confirmed that the mutation arose de novo in the carrier mother. NAA10 encodes the catalytic subunit of the major human N-terminal acetylation complex NatA. In vitro assays for the p.Tyr43Ser mutant enzyme showed a significant decrease in catalytic activity and reduced stability compared to wild-type Naa10 protein. NAA10 has previously been associated with Ogden syndrome, Lenz microphthalmia syndrome and non-syndromic developmental delay. Our findings expand the clinical spectrum of NAA10 and suggest that the proposed correlation between mutant Naa10 enzyme activity and phenotype severity is more complex than anticipated; the p.Tyr43Ser mutant enzyme has less catalytic activity than the p.Ser37Pro mutant associated with lethal Ogden syndrome but results in a milder phenotype. Importantly, we highlight the need for cardiac assessment in males and females with NAA10 variants as both patients and carriers can have long QT.

ChemInform Abstract: Selective Thiolative Lactonization of Internal Alkynes Bearing a Hydroxyl Group with Carbon Monoxide and Organic Disulfides Catalyzed by Transition‐Metal Complexes

AbstractPd(PPh3)4 or Co2(CO)8

Photolysis of triruthenium μ3-alkyne complexes capped by a μ3-oxo ligand

Triruthenium alkyne complexes containing a triply bridging oxo ligand, (Cp*Ru)3{μ3-η2(||)-RCCH}(μ3-O)(μ-H) (9a, R = Ph; 9b, R = n-Pr; 9c, R = t-Bu), were synthesized. Although 9 was quite stable under thermal conditions, photolysis by 313 nm light caused the transformation of 9 into the μ3-acetylido complexes, (Cp*Ru)3(μ3-η2:η2-CCR)(μ3-O) (10a–c). In contrast, a 47-electron alkyne complex, (Cp*Ru)3{μ3-η2:η2(⊥)-PhCCPh}(μ3-O) (11d), in which the alkyne ligand was coordinated to one of the Ru–Ru bonds in a perpendicular fashion, was obtained by the irradiation of the internal alkyne complex (Cp*Ru)3{μ3-η2(||)-PhCCPh}(μ3-O)(μ-H) (9d) by hydride abstraction. Dynamic property of the μ3-acetylido ligand, so called “edge hopping” motion, was also studied using variable-temperature 1H NMR techniques, which clearly demonstrated that the mobility of the acetylido ligand increases along with the bulkiness of the substituent on the β-carbon.

Spontaneous Formation of an η2‐C, S‐Thioketene Complex in Pursuit of Tungsten(IV)‐Sulfanylalkyne Complexes

AbstractThe oxo tungsten(IV) alkyne complexes [Tp′W(O)(I)(η2‐C2Ph2)] (1), [Tp′W(O)(I){η2‐C2(SC2H4SiMe3)2}] (2), and [Tp′W(O)(I){η2‐C2(SBn)2}] (3) [Tp′ = hydridotris(3, 5‐dimethylpyrazolyl)borate, Bn = benzyl] were synthesized from [Tp′W(O)(CO)(I)]. All three compounds were fully characterized including structure determination by X‐ray diffraction analysis. Further elucidation of these reactions led to the isolation of several by‐products including an unexpected tungsten(IV) thioketene complex [Tp′W(O)(I){η2‐S = C=C(H)(SBn)}] (4), which is formed by removal of one Bn group from the alkyne, and dinuclear [Tp′W(O)(I)]2(μ‐O) (6). Both complexes were also fully characterized. X‐ray diffraction analysis reveals an η2‐S, C side‐on binding mode for 4 and a planar O–W–O–W–O moiety for 6. In addition, by changing the solvent from THF to dichloromethane formation of the chiral dihalogen complex [Tp′W(O)(Cl)(I)] (5) was proven.

Second hyperpolarizability of delta shaped disubstituted acetylene complexes of beryllium, magnesium, and calcium.

Present theoretical study involves the delta shape complexes of beryllium, magnesium, and calcium where the metal atom interacts perpendicularly with disubstituted acetylene. Most of the complexes are found to be fairly stable. The dependence of second-hyperpolarizability on the basis set with increasing polarization and diffuse functions has been examined which showed the importance of 'f-type' type polarization function for heavy metal (Mg, Ca) and 'd-type' polarization function for beryllium. Larger second hyperpolarizability has been predicted for complexes having significant ground state polarization and low lying excited states favoring strong electronic coupling. Transition energy plays the most significant role in modulating the second hyperpolarizability.

Intramolecular competition between n-pair and π-pair hydrogen bonding: Microwave spectrum and internal dynamics of the pyridine-acetylene hydrogen-bonded complex.

a-type rotational spectra of the hydrogen-bonded complex formed from pyridine and acetylene are reported. Rotational and (14)N hyperfine constants indicate that the complex is planar with an acetylenic hydrogen directed toward the nitrogen. However, unlike the complexes of pyridine with HCl and HBr, the acetylene moiety in HCCH-NC5H5 does not lie along the symmetry axis of the nitrogen lone pair, but rather, forms an average angle of 46° with the C2 axis of the pyridine. The a-type spectra of HCCH-NC5H5 and DCCD-NC5H5 are doubled, suggesting the existence of a low lying pair of tunneling states. This doubling persists in the spectra of HCCD-NC5H5, DCCH-NC5H5, indicating that the underlying motion does not involve interchange of the two hydrogens of the acetylene. Single (13)C substitution in either the ortho- or meta-position of the pyridine eliminates the doubling and gives rise to separate sets of spectra that are well predicted by a bent geometry with the (13)C on either the same side ("inner") or the opposite side ("outer") as the acetylene. High level ab initio calculations are presented which indicate a binding energy of 1.2 kcal/mol and a potential energy barrier of 44 cm(-1) in the C2v configuration. Taken together, these results reveal a complex with a bent hydrogen bond and large amplitude rocking of the acetylene moiety. It is likely that the bent equilibrium structure arises from a competition between a weak hydrogen bond to the nitrogen (an n-pair hydrogen bond) and a secondary interaction between the ortho-hydrogens of the pyridine and the π electron density of the acetylene.

Polymer Soft-Landing Isolation of Acetylene on Polystyrene and Poly(vinylpyridine): A Novel Approach to Probing Hydrogen Bonding in Polymers.

Hydrogen-bonded complexes of acetylene (Ac) with the polymers polystyrene (PS), poly(4-vinylpyridine) (P4VP), and poly(2-vinylpyridine) (P2VP) have been characterized for the first time at 16 K in a "polymer soft-landing isolation" experiment which is being pioneered in our research laboratory. In particular, changes in vibrational modes of Ac provide ample evidence for hydrogen-bonded complexes between Ac and the phenyl groups of PS or the pyridyl groups of P4VP and P2VP. With PS, the proton on the top Ac molecule of the classic T-shaped Ac dimer interacts with the π cloud of the benzene (Bz) ring to form a C-H---π interaction, while the π cloud of the lower Ac forms a second C-H---π interaction with a proton on the Bz ring. An analogous (ring)1-(Ac)2 double interaction occurs between an Ac dimer and the pyridine (Pyr) rings on both P2VP and P4VP, yielding a C-H---N and C-H---π interaction. With P4VP and P2VP a second bridged (ring)2-(Ac)2 product is formed, with the Ac dimer forming nearly collinear C-H---N hydrogen bonds to adjacent Pyr rings. On P2VP this bridged product is the only one after extensive annealing. These complexes in which Ac acts as both proton donor and acceptor have not previously been observed in conventional matrix isolation experiments. This study is the second from our laboratory employing this method, which represents a slight modification of the traditional matrix isolation technique.

ChemInform Abstract: Niobium Complexes in Organic Transformations: From Stoichiometric Reactions to Catalytic [2 + 2 + 2] Cycloaddition Reactions

AbstractReview: [57 refs.

Competitive Inhibition Can Linearize Dose-Response and Generate a Linear Rectifier

Many biological responses require a dynamic range that is larger than standard bi-molecular interactions allow, yet the also ability to remain off at low input. Here we mathematically show that an enzyme reaction system involving a combination of competitive inhibition, conservation of the total level of substrate and inhibitor, and positive feedback can behave like a linear rectifier-that is, a network motif with an input-output relationship that is linearly sensitive to substrate above a threshold but unresponsive below the threshold. We propose that the evolutionarily conserved yeast SAGA histone acetylation complex may possess the proper physiological response characteristics and molecular interactions needed to perform as a linear rectifier, and we suggest potential experiments to test this hypothesis. One implication of this work is that linear responses and linear rectifiers might be easier to evolve or synthetically construct than is currently appreciated.

Extended Threefold‐Symmetric Second‐Harmonic‐Generation Chromophores Based on 1,3,5‐Trisubstituted Benzene Complexes

The elongation of the π system of a donor–π–acceptor (D–π–A) chromophore has often proven to be beneficial for its nonlinear optical (NLO) activity. Against this background, different alkynyl protecting groups such as organosilyl and dicobalt hexacarbonyl functions were investigated with respect to their ability to enable the coordination of an electron-withdrawing CpRu+ fragment (Cp = cyclopentadienyl) to a threefold ethynyl-substituted benzene ring, acting as a potential 2D NLOphore, without undesired side reactions. In addition, the influence of the perpendicularly coordinated CpRu+ unit on the NLO properties was examined. The obtained organometallic triisopropylsilyl-substituted benzene ruthenium complex and the multinuclear dicobalt hexacarbonyl protected ferrocene complex were fully characterized. Owing to the problems during the purification of the trimethylsilyl-protected benzene ruthenium complex and the subsequent deprotection to the free alkyne complex, it was not possible to fully characterize those complexes. The introduction of the CpRu+ fragment was sensitive to the steric demands of the benzene substituents but beneficial for the generation of NLO activity. The first hyperpolarizabilities of the triisopropyl and dicobalt hexacarbonyl complexes were investigated by hyper-Rayleigh scattering. The molecular structures were characterized by X-ray crystallography and infrared (IR) spectroscopy. The structures and IR spectra were compared with Kohn–Sham density functional theory calculations.

ChemInform Abstract: Synthesis, Structure, and Reactivity of Niobium and Tantalum Alkyne Complexes

AbstractReview: 110 refs.

Plant coumarins: XV. Oreoselone in the synthesis of 3-[(Z)-alkenyl]- and 3-(1H-1,2,3-triazol-4-yl)psoralens

Sonogashira reaction of 2-isopropyl-3-(trifluoromethanesulfonyloxy)psoralen with terminal arylacetylenes gave 2-isopropyl-3-(arylethynyl)psoralens which were converted into the corresponding Z-alkenes by reduction with hydrogen in the presence of Lindlar catalyst or by thermal decomposition of preliminarily prepared Ti(II)–alkyne complexes. The reaction of 2-isopropyl-3-(trifluoromethanesulfonyloxy)psoralen with trimethylsilylacetylene afforded 2-isopropyl-3-[(trimethylsilyl)ethynyl]psoralen which reacted with 4-(ω-azidoalkyl) phenols in the presence of copper(I) bromide and triethylamine to produce 3-{1-[ω-(4-hydroxyaryl)-alkyl]-1H-1,2,3-triazol-4-yl}-2-isopropylpsoralens.

Synthesis and Reactivity of Oxorhenium(V) Methyl, Benzyl, and Phenyl Complexes with CO: Implications for a Unique Mechanism for Migratory Insertion

The complexes [(DAAm)Re(O)(R)] [DAAm = N,N-bis(2-arylaminoethyl)methylamine; aryl = C6F5], 1, R = Me; 3a–d (R = benzyl, a; 4-methylbenzyl, b; 4-fluorobenzyl, c; 4-methoxybenzyl, d); and 4, R = Ph, were synthesized. CO insertion into the Re–R bond in 1 and 3a–d resulted in the formation of the acetyl complex, 2, and the (aryl)acetyl complexes, 5a–d respectively. The formation of 5a–d proceeded at a faster rate (7 h) than the formation of 2 (72 h) under the same conditions. No reaction was observed however for the phenyl complex 4 with CO. Kinetics for CO insertion into the various Re–R bonds were examined, and the experimental rate law was determined to be Rate = kobs[Re][CO]. The activation parameters for CO insertion into 1 and 3a were determined to be ΔG⧧(298 K) = 24(1). The enthalpy of activation ΔH⧧ was determined to be 9(1) and 10(3) kcal/mol for 1 and 3a, respectively, and the entropy of activation, ΔS⧧, was −49(2) and −36(4) cal/mol·K. Computational studies (M06) are consistent with the hypothesis ...

Evaluating the Effect of Catalyst Nuclearity in Ni-Catalyzed Alkyne Cyclotrimerizations.

An evaluation of catalyst nuclearity effects in Ni-catalyzed alkyne oligomerization reactions is presented. A dinuclear complex, featuring a Ni-Ni bond supported by a naphthyridine-diimine (NDI) ligand, promotes rapid and selective cyclotrimerization to form 1,2,4-substituted arene products. Mononickel congeners bearing related N-donor chelates (2-iminopyridines, 2,2'-bipyridines, or 1,4,-diazadienes) are significantly less active and yield complex product mixtures. Stoichiometric reactions of the dinickel catalyst with hindered silyl acetylenes enable characterization of the alkyne complex and the metallacycle that are implicated as catalytic intermediates. Based on these experiments and supporting DFT calculations, the role of the dinuclear active site in promoting regioselective alkyne coupling is discussed. Together, these results demonstrate the utility of exploring nuclearity as a parameter for catalyst optimization.

Mapping the Interactions of I2 , I(.) , I(-) , and I(+) with Alkynes and Their Roles in Iodocyclizations.

A combination of experiment and theory has been used to explore the mechanisms by which molecular iodine (I2 ) and iodonium ions (I(+) ) activate alkynes towards iodocyclization. Also included in the analysis are the roles of atomic iodine (I(.) ) and iodide ion (I(-) ) in mediating the competing addition of I2 to the alkyne. These studies show that I2 forms a bridged I2 -alkyne complex, in which both alkyne carbons are activated towards nucleophilic attack, even for quite polarized alkynes. By contrast, I(+) gives unsymmetrical, open iodovinyl cations, in which only one carbon is activated toward nucleophilic attack, especially for polarized alkynes. Addition of I2 to alkynes competes with iodocyclization, but is reversible. This fact, together with the capacity of I2 to activate both alkyne carbons towards nucleophilic attack, makes I2 the reagent of choice (superior to iodonium reagents) for iodocyclizations of resistant substrates. The differences in the nature of the activated intermediate formed with I2 versus I(+) can also be exploited to accomplish reagent-controlled 5-exo/6-endo-divergent iodocyclizations.

Niobium Complexes in Organic Transformations: From Stoichiometric Reactions to Catalytic [2+2+2] Cycloaddition Reactions

AbstractNiobium complexes in organic reactions have received a lot of attention in recent years. Niobium is one of the early transition metals, which possess unique reactivity distinct from that of other transition metals. This review focuses mainly on stoichiometric reactions and catalytic reactions involving niobium complexes. In particular, recent results relating to NbV‐mediated or NbIII‐catalyzed [2+2+2] cycloaddition of unsaturated compounds (alkyne, alkenes, nitriles, and isocyanates) are mainly presented in this review. In one example of a set of catalytic reactions involving a low‐valent niobium species, the reaction between NbCl5 and tris(trimethylsilyl)silane generated a low‐valent niobium(III) species, and this promoted [2+2+2] cycloaddition of terminal alkynes and olefins to provide cyclohexa‐1,3‐dienes. In addition, the use of low‐valent niobium(III) species in stoichiometric reactions has also been reported. Many of these reactions are carried out by formation of Nb–alkyne complexes through reactions between low‐valent niobium(III) and internal alkynes. Some examples of the use of Nb complexes as Lewis acids have also been reported. In these reactions, the valence of the Nb complexes is V.

Ring-Closing Metathesis of Co2(CO)6-Alkyne Complexes for the Synthesis of 11-Membered Dienediynes: Overcoming Thermodynamic Barriers.

The feasibility of ring-closing metathesis (RCM) as a synthetic entry to 10- and 11-membered dienediynes fused to a benzothiophene core was explored by experimental and theoretical investigations. An established sequence of iodocyclization of o-(buta-1,3-diynyl)thioanisoles followed by Sonogashira coupling to form diethynylbenzothiophenes was used to synthesize terminal benzothiophene-fused enediyne diolefins as substrates for RCM. Encountering an unexpected lack of reactivity of these substrates under standard RCM conditions, we applied DFT calculations to reveal that the underlying cause was a positive change in Gibbs free energy. The change in Gibbs free energy was also found to be positive for RCM of indole- and benzannulated terminal diolefins when affording smaller than 12-membered rings. We found that modification of the enediyne-diolefin substrate as the Co2(CO)6-alkyne complex allowed the target benzothiophene-fused 11-membered dienediyne to be obtained via RCM; the alkyne complexation strategy therefore provides one valid technique for overcoming challenges to macrocyclization of this kind.

ChemInform Abstract: Advancements in the Mechanistic Understanding of the Copper‐Catalyzed Azide‐Alkyne Cycloaddition

AbstractReview: 232 refs.