Facile Cleavage Research Articles

Phenylselenolate mercury alkyl compounds, PhSeHgMe and PhSeHgEt: Molecular structures, protolytic Hg–C bond cleavage and phenylselenolate exchange

The phenylselenolate mercury alkyl compounds, PhSeHgMe and PhSeHgEt, have been structurally characterized by X-ray diffraction, thereby demonstrating that both compounds are monomeric with approximately linear coordination geometries; the mercury centers do, nevertheless, exhibit secondary Hg⋯Se intermolecular interactions that serve to increase the coordination number in the solid state. The ethyl derivative, PhSeHgEt, undergoes facile protolytic cleavage of the Hg–C bond to release ethane at room temperature, whereas PhSeHgMe exhibits little reactivity under similar conditions. Interestingly, the cleavage of the Hg–C bond of PhSeHgEt is also more facile than that of the thiolate analog, PhSHgEt, which demonstrates that coordination by selenium promotes protolytic cleavage of the mercury–carbon bond. The phenylselenolate compounds PhSeHgR (R=Me, Et) also undergo degenerate exchange reactions with, for example, PhSHgR and RHgCl. In each case, the alkyl groups preserve coupling to the 199Hg nuclei, thereby indicating that the exchange process involves metathesis of the Hg–SePh/Hg–X groups rather than metathesis of the Hg–R/Hg–R groups.

Bromine isotopic signature facilitates de novo sequencing of peptides in free-radical-initiated peptide sequencing (FRIPS) mass spectrometry.

We recently showed that free-radical-initiated peptide sequencing mass spectrometry (FRIPS MS) assisted by the remarkable thermochemical stability of (2,2,6,6-tetramethyl-piperidin-1-yl)oxyl (TEMPO) is another attractive radical-driven peptide fragmentation MS tool. Facile homolytic cleavage of the bond between the benzylic carbon and the oxygen of the TEMPO moiety in o-TEMPO-Bz-C(O)-peptide and the high reactivity of the benzylic radical species generated in •Bz-C(O)-peptide are key elements leading to extensive radical-driven peptide backbone fragmentation. In the present study, we demonstrate that the incorporation of bromine into the benzene ring, i.e. o-TEMPO-Bz(Br)-C(O)-peptide, allows unambiguous distinction of the N-terminal peptide fragments from the C-terminal fragments through the unique bromine doublet isotopic signature. Furthermore, bromine substitution does not alter the overall radical-driven peptide backbone dissociation pathways of o-TEMPO-Bz-C(O)-peptide. From a practical perspective, the presence of the bromine isotopic signature in the N-terminal peptide fragments in TEMPO-assisted FRIPS MS represents a useful and cost-effective opportunity for de novo peptide sequencing.

The identification of disulfides in ricin D using proteolytic cleavage followed by negative-ion nano-electrospray ionization mass spectrometry of the peptide fragments.

To use negative-ion nano-electrospray ionization mass spectrometry of peptides from the tryptic digest of ricin D, to provide sequence information; in particular, to identify disulfide position and connectivity. Negative-ion fragmentations of peptides from the tryptic digest of ricin D was studied using a Waters QTOF2 mass spectrometer operating in MS and MS(2) modes. Twenty-three peptides were obtained following high-performance liquid chromatography and studied by negative-ion mass spectrometry covering 73% of the amino-acid residues of ricin D. Five disulfide-containing peptides were identified, three intermolecular and two intramolecular disulfide-containing peptides. The [M-H](-) anions of the intermolecular disulfides undergo facile cleavage of the disulfide units to produce fragment peptides. In negative-ion collision-induced dissociation (CID) these source-formed anions undergo backbone cleavages, which provide sequencing information. The two intramolecular disulfides were converted proteolytically into intermolecular disulfides, which were identified as outlined above. The positions of the five disulfide groups in ricin D may be determined by characteristic negative-ion cleavage of the disulfide groups, while sequence information may be determined using the standard negative-ion backbone cleavages of the resulting cleaved peptides. Negative-ion mass spectrometry can also be used to provide partial sequencing information for other peptides (i.e. those not containing Cys) using the standard negative-ion backbone cleavages of these peptides.

Catalytic α-monoallylation of aryl acetonitriles.

α-Cyano aldehydes undergo selective transition-metal-catalyzed monoallylation to provide α-allylated nitriles. The transformation leads to linear substitution products with palladium catalysts or branched allylated nitriles using an iridium catalyst. Facile TBD-catalyzed retro-Claisen cleavage is leveraged to attain selective monoallylation.

Photo‐induced thiol‐ene polysulfide‐crosslinked materials with tunable thermal and mechanical properties

ABSTRACTPhoto‐induced thiol‐ene crosslinked polymeric networks have been extensively explored in constructing a variety of new materials with enhanced mechanical properties for optical, biomedical, and sensing applications. Toward the broad applications, however, tunable mechanical properties are greatly desired. Here, an effective approach utilizing high‐molecular‐weight methacrylate copolymers having pendant thiol and vinyl groups (MCPsh and MCPenes) to modulate thermal and mechanical properties of photo‐induced thiol‐ene crosslinked materials is reported. The MCP copolymers are synthesized by an industrially friendly polymerization method, followed by post‐modification including either a facile coupling reaction or reductive cleavage. Upon UV irradiation, thiol‐ene reactive blends of MCPsh and MCPenes yield highly crosslinked materials through the formation of flexible sulfide linkages. These polysulfide‐crosslinked materials based on rigid MCP backbones exhibit enhanced mechanical properties. Further, their thermal and mechanical properties are tuned by modulating monomer compositions of MCPs as well as varying numbers of pendant SH or vinyl groups (i.e., extent of crosslinking densities). This approach is versatile and effective for development of high performance polymeric materials. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 3060–3068

Imaging molecular interaction of NO on Cu(110) with a scanning tunneling microscope.

Molecular interaction on metal surfaces is one of the central issues of surface science for the microscopic understanding of heterogeneous catalysis. In this Personal Account, I review the recent studies on NO/Cu(110) employing a scanning tunneling microscope (STM) to probe and control the molecule-molecule interaction on the surface. An individual NO molecule was observed as a characteristic dumbbell-shaped protrusion, visualizing the 2π* orbital. By manipulating the intermolecular distance with the STM, the overlap of the 2π* orbital between two NO molecules was controlled. The interaction causes the formation of the bonding and antibonding orbitals below and above the Fermi level, respectively, as a function of the intermolecular distance. The 2π* orbital also plays a role in the reaction of NO with water molecules. A water molecule donates a H-bond to NO, giving rise to the down-shift of the 2π* level below the Fermi level. This causes electron transfer from the substrate to NO, weakening, and eventually rupturing, the N-O bond. The facile bond cleavage by water molecules has implications for the catalytic reduction of NO under ambient conditions.

Synthetic control of isolated, single functional groups on silica surfaces.

We report control of the density of isolated, single functional groups in homogeneously mixed trichloroalkyl silanes on various silica surfaces. The functional groups are covalently bound to a silane derived from the Rink resin. This Rink-silane is reactive to any nucleophile. Control over the density of functional groups is achieved by diluting the immersion solution containing the Rink-silane with an inert silane, octadecyltrichlorsilane. The isolated nature of the functional groups is confirmed by the stochastic blinking of fluorescent single boron-dipyrromethane dyes imaged in total internal reflection geometry. The robust character of silane monolayers allows facile covalent binding and cleavage of molecular species from silica surfaces as well as general synthetic transformations to be conducted. This is shown by the covalent attachment and then cleavage of a naphthalene chromophore. This low-cost and scalable platform has great potential for use in sensing, molecular electronics, semiconductor processing, and the investigation of fundamental processes in catalysis and the kinetics of molecular association.

Fragmentation of Electrospray-Produced Deprotonated Ions of Oligodeoxyribonucleotides Containing an Alkylated or Oxidized Thymidine

Alkylation and oxidation constitute major routes of DNA damage induced by endogenous and exogenous genotoxic agents. Understanding the biological consequences of DNA lesions often necessitates the availability of oligodeoxyribonucleotide (ODN) substrates harboring these lesions, and sensitive and robust methods for validating the identities of these ODNs. Tandem mass spectrometry is well suited for meeting these latter analytical needs. In the present study, we evaluated how the incorporation of an ethyl group to different positions (i.e., O(2), N3, and O(4)) of thymine and the oxidation of its 5-methyl carbon impact collisionally activated dissociation (CAD) pathways of electrospray-produced deprotonated ions of ODNs harboring these thymine modifications. Unlike an unmodified thymine, which often manifests poor cleavage of the C3'-O3' bond, the incorporation of an alkyl group to the O(2) position and, to a much lesser extent, the O(4) position, but not the N3 position of thymine, led to facile cleavage of the C3'-O3' bond on the 3' side of the modified thymine. Similar efficient chain cleavage was observed when thymine was oxidized to 5-formyluracil or 5-carboxyluracil, but not 5-hydroxymethyluracil. Additionally, with the support of computational modeling, we revealed that proton affinity and acidity of the modified nucleobases govern the fragmentation of ODNs containing the alkylated and oxidized thymidine derivatives, respectively. These results provided important insights into the effects of thymine modifications on ODN fragmentation.

ChemInform Abstract: Copper‐Catalyzed Domino Cycloaddition/C—N Coupling/Cyclization/(C—H Arylation): An Efficient Three‐Component Synthesis of Nitrogen Polyheterocycles.

A cat of all trades: A single copper catalyst promoted up to three reaction steps with separate catalytic cycles in a domino sequence (azide-alkyne cycloaddition/Goldberg amidation/Camps cyclization/(CH arylation)) for the rapid construction of complex heterocycles from three simple components under mild conditions. Facile cleavage of the triazole ring enables further elaboration of the condensation products.

Identification of fatty acid steryl esters in margarine and corn using direct flow injection ESI-MSn ion trap-mass spectrometry

An approach for identification of steryl esters using flow injection ESI-MS2 and ESI-MS3 ion trap mass spectrometry has been developed. Sterols and other lipids extracted from samples of margarine and corn using hexane were subjected to solid phase extraction. The steryl ester fraction was eluted with hexane:diethyl ether (98:2, v/v). In ESI-MS experiments fatty acid steryl esters were easily detected as ammoniated adducts [M+NH4]+ using ammonium acetate as dopant. Steryl esters including molecular isomers could be identified using ESI-QIT MS2 by the facile ester cleavage whereby the charge resides with the steryl moiety. For positive confirmation of the sterol group, ESI-QIT MS3 was carried out on the intact steryl fragmentation cation. The resulting CID spectra of the steryl cation were found to be unique and similar to those from APCI-QIT MS2 CID of free sterol standards. All major steryl esters were identified in both margarine (12 esters) and corn (7 esters) extracts. Based on the ion intensity of the ESI-MS spectra the major steryl esters in margarine were: β-sitosteryl stearate, β-sitosteryl oleate, β-sitosteryl linoleate, campesteryl stearate and campesteryl linoleate. In corn they were: β-sitosteryl oleate, campesteryl stearate, campesteryl oleate and stigmasteryl linoleate. This method can be very useful for rapid and complete identification of fatty acid steryl esters extracted from other biological samples.

Disclosure of Key Stereoelectronic Factors for Efficient H2 Binding and Cleavage in the Active Site of [NiFe]-Hydrogenases

A comparative analysis of a series of DFT models of [NiFe]-hydrogenases, ranging from minimal NiFe clusters to very large systems including both the first and second coordination sphere of the bimetallic cofactor, was carried out with the aim of unraveling which stereoelectronic properties of the active site of [NiFe]-hydrogenases are crucial for efficient H2 binding and cleavage. H2 binding to the Ni-SIa redox state is energetically favored (by 4.0 kcal mol(-1)) only when H2 binds to Ni, the NiFe metal cluster is in a low spin state, and the Ni cysteine ligands have a peculiar seesaw coordination geometry, which in the enzyme is stabilized by the protein environment. The influence of the Ni coordination geometry on the H2 binding affinity was then quantitatively evaluated and rationalized analyzing frontier molecular orbitals and populations. Several plausible reaction pathways leading to H2 cleavage were also studied. It turned out that a two-step pathway, where H2 cleavage takes place on the Ni-SIa redox state of the enzyme, is characterized by very low reaction barriers and favorable reaction energies. More importantly, the seesaw coordination geometry of Ni was found to be a key feature for facile H2 cleavage. The discovery of the crucial influence of the Ni coordination geometry on H2 binding and activation in the active site of [NiFe]-hydrogenases could be exploited in the design of novel biomimetic synthetic catalysts.

Ru(II) thioether complexes with dangling pyridine ligands

Through two different methods, new Ru(II) polypyridyl complexes were prepared in an attempt to replicate previously reported heptacoordinate Ru(II) syntheses. The tetradentate thioethers, 1,8-bis(2′-pyridyl)-3,7-dithianonane (Pdto), 1,9-bis(2′-pyridyl)-3,7-dithianonane (Pdtn), and 1,10-bis(2′-pyridyl)-3,8-dithiadecane (Pdtd), were used to form dinuclear ruthenium(II) complexes of the type [{Ru(L1)}2(μ-Cl)2]2+via reaction with RuCl3·xH2O. Upon reaction of the dinuclear complexes with the triimine ligand 2,6-bis(N′-methyl-benzimidazolyl)pyridine (Me2Bzimpy), facile symmetrical bridge cleavage occurs, producing mononuclear complexes of the form [Ru(L1)(L2)]2+, where L1 is one of the three tetradentate thioether ligands and L2 is the tridentate triimine. A second method of producing the mononuclear [Ru(L1)(L2)]2+ complexes involves the reaction of Ru(L2)Cl3 with L1 under ethanolic conditions. In such mononuclear complexes, one of the pyridine arms of the tetradentate thioether is forced to be uncoordinated, due to the firmly hexacoordinate nature of Ru(II). A similar experiment was conducted using the pentadentate thioether 1,11-bis(2′-pyridyl)-3,6-9-dithianonane (Pttu) and the diimine Phen, forming the stable hexacoordinate [Ru(Pttu)(Phen)]2+ complex. The mononuclear complexes exhibit single-electron Ru(II)→Ru(III) oxidative response, in the range of +825 to +845mV versus APE, involving the removal from an electron from the t2g orbital set.

Copper‐Catalyzed Domino Cycloaddition/CN Coupling/Cyclization/(CH Arylation): An Efficient Three‐Component Synthesis of Nitrogen Polyheterocycles

A cat of all trades: A single copper catalyst promoted up to three reaction steps with separate catalytic cycles in a domino sequence (azide-alkyne cycloaddition/Goldberg amidation/Camps cyclization/(CH arylation)) for the rapid construction of complex heterocycles from three simple components under mild conditions. Facile cleavage of the triazole ring enables further elaboration of the condensation products.

A Fragile Zwitterionic Phosphasilene as a Transfer Agent of the Elusive Parent Phosphinidene (:PH)

The simplest parent phosphinidene, :PH (1), has been observed only in the gas phase or low temperature matrices and has escaped rigorous characterization because of its high reactivity. Its liberation and transfer to an unsaturated organic molecule in solution has now been accomplished by taking advantage of the facile homolytic bond cleavage of the fragile Si═P bond of the first zwitterionic phosphasilene LSi=PH (8) (L = CH[(C═CH2)CMe(NAr)2]; Ar = 2,6-(i)Pr2C6H3). The latter bears two highly localized lone pairs on the phosphorus atom due to the LSi═PH ↔ LSi(+)-PH(-) resonance structures. Strikingly, the dissociation of 8 in hydrocarbon solutions occurs even at room temperature, affording the N-heterocyclic silylene LSi: (9) and 1, which leads to oligomeric [PH]n clusters in the absence of a trapping agent. However, in the presence of an N-heterocyclic carbene as an unsaturated organic substrate, the fragile phosphasilene 8 acts as a :PH transfer reagent, resulting in the formation of silylene 9 and phosphaalkene 11 bearing a terminal PH moiety.

Facile cleavage of phenyl groups from BiPh3 in its reactions with Os3(CO)10(NCMe)2 and evidence for localization of π-bonding in a bridging benzyne ligand

Three new compounds were obtained from the reaction of Os3(CO)10(NCMe)2, 1 with BiPh3 in a methylene chloride solution at reflux. These have been identified as Os3(CO)10(μ3-C6H4), 3, Os3(CO)10Ph(μ-η2- OCPh), 4, and HOs6(CO)20(μ-η2-C6H4)(μ4-Bi), 6. Two other products Os2(CO)8(μ-BiPh), 2, and HOs5(CO)18(μ-η2-C6H4)(μ4-Bi), 5 were obtained previously from the reaction of Os3(CO)11(NCMe) with BiPh3. Cleavage of the phenyl groups from the BiPh3 was the dominant reaction pathway and two of the products 3 and 4 contain rings but no bismuth. Each of the new compounds was characterized structurally by single-crystal X-ray diffraction methods. Compound 3 contains a triply-bridging benzyne (C6H4) ligand that exhibits a pattern of alternating long and short C–C bonds that can be attributed to partial localization of the π-bonding in the C6 ring. The localization in the π-bonding in the ring is supported by DFT calculations. Compound 4 contains a triangular cluster of three osmium atoms with a bridging benzoyl ligand and a terminally coordinated phenyl ligand. Compound 6 contains six osmium atoms divided into two groups of four and two and the two groups are linked by a spiro-bridging bismuth atom. The group of two osmium atoms contains a bridging C6H4 ligand. When heated, compound 4 was converted into 3 and the compound Os3(CO)10(μ-η2-OCPh)2, 7. Compound 7 contains two bridging benzoyl ligands.

Development of asymmetric deacylative allylation.

Herein we present the development of asymmetric deacylative allylation of ketone enolates. The reaction directly couples readily available ketone pronucleophiles with allylic alcohols using facile retro-Claisen cleavage to form reactive intermediates in situ. The simplicity and robustness of the reaction conditions is demonstrated by the preparation of >6 g of an allylated tetralone from commercially available materials. Furthermore, use of nonracemic PHOX ligands allows intermolecular formation of quaternary stereocenters directly from allylic alcohols.

The ornithine effect in peptide cation dissociation

Facile cleavage C-terminal to ornithine residues in gas phase peptides has been observed and termed the ornithine effect. Peptides containing internal or C-terminal ornithine residues, which are formed from deguanidination of arginine in solution, were fragmented to produce either a y-ion or water loss, respectively, and the complementary b-ion. The fragmentation patterns of several peptides containing arginine were compared to those of the ornithine analogues. Conversion of arginine to ornithine results in a decrease of the gas phase proton affinity of the residue, thereby increasing the mobility of the ionizing proton. This alteration allows the nucleophilic amine to facilitate a neighboring group reaction to induce a cleavage of the adjacent amide bond. The selective cleavage at the ornithine residue is proposed to result from the highly favorable generation of a six-membered lactam ring. The ornithine effect was compared with the well-known proline and aspartic acid effects in peptide fragmentation using angiotensin II, DRVYIHPF and the ornithine analogue, DOVYIHPF. Under conditions favorable to either the aspartic acid (i.e. singly protonated peptide) or proline effect (i.e. doubly protonated peptide), the ornithine effect was consistently observed to be the more favorable fragmentation pathway. The highly selective nature of the ornithine effect opens up the possibility for conversion of arginine to ornithine residues to induce selective cleavages in polypeptide ions. Such an approach may complement strategies that seek to generate non-selective cleavages of the related peptides.

ChemInform Abstract: In situ Generation of Hydroperoxide by Oxidation of Benzhydrols to Benzophenones Using Sodium Hydride under Oxygen Atmosphere: Use for the Oxidative Cleavage of Cyclic 1,2‐Diketones to Dicarboxylic Acids.

Abstract A facile oxidative cleavage of cyclic 1,2-diketones 1 to dicarboxylic acids 3 with hydroperoxide generated in situ has been developed. In situ generation of hydroperoxide was effected by the oxidation of 4,4′-dichlorobenzhydrol 2f to 4,4′-dichlorobenzophenone 4f using sodium hydride under oxygen atmosphere.

Facile ring cleavage of basic azetidines

Azetidines containing a basic ring nitrogen atom have been shown to undergo facile ring cleavage to afford 3-halo-1-amino propane derivatives upon exposure to alkyl bromides and acyl chlorides under certain conditions. The rate of ring cleavage appears to be determined largely by the rate at which quaternization of the azetidine nitrogen atom occurs. Alkylation of NH azetidines to afford N-alkyl azetidines can be carried out in synthetically useful yields if reaction times are kept short. As the free base, azetidines may undergo spontaneous oligomerization with concomitant ring cleavage.

Reactivity Models of Hydrogen Activation by Frustrated Lewis Pairs: Synergistic Electron Transfers or Polarization by Electric Field?

Two alternative qualitative reactivity models have recently been proposed to interpret the facile heterolytic cleavage of H2 by frustrated Lewis pairs (FLPs). Both models assume that the reaction takes place via reactive intermediates with preorganized acid/base partners; however, they differ in the mode of action of the active centers. In the electron transfer (ET) model, the hydrogen activation is associated with synergistic electron donation processes with the simultaneous involvement of active centers and the bridging hydrogen, showing similarity to transition-metal-based and other H2-activating systems. In contrast, the electric field (EF) model suggests that the heterolytic bond cleavage occurs as a result of polarization by the strong EF present in the cavity of the reactive intermediates. To assess the applicability of the two conceptually different mechanistic views, we examined the structural and electronic rearrangements as well as the EFs along the H2 splitting pathways for a representative set of reactions. The analysis reveals that electron donations developing already in the initial phase are general characteristics of all studied reactions, and the related ET model provides qualitative interpretation for the main features of the reaction pathways. On the other hand, several arguments have emerged that cast doubt on the relevance of EF effects as a conceptual basis in FLP-mediated hydrogen activation.