Search

A series of cyclometalated iridium(III) complexes with either 4-(2-pyridyl)-1,2,3-triazole or 1-(2-picolyl)-1,2,3-triazole ancillary ligands to give complexes with either 5- or 6-membered chelate rings were synthesized and characterized by a combination of X-ray crystallography, electron spin ionization-high-resolution mass spectroscopy (ESI-HRMS), and nuclear magnetic resonance (NMR) spectroscopy. The electronic properties of the complexes were probed using absorption and emission spectroscopy, as well as cyclic voltammetry. The relative stability of the complexes formed from each ligand class was measured, and their excited-state properties were compared. The emissive properties are, with the exception of complexes that contain a nitroaromatic substituent, insensitive to functionalization of the ancillary pyridyl-1,2,3-triazole ligand but tuning of the emission maxima was possible by modification of the cyclometalating ligands. It is possible to prepare a wide range of optimally substituted pyridyl-1,2,3-triazoles using copper Cu(I)-catalyzed azide alkyne cycloaddition, which is a commonly used "click" reaction, and this family of ligands represent an useful alternative to bipyridine ligands for the preparation of luminescent iridium(III) complexes. [ABSTRACT FROM AUTHOR]

Tracking of Pt(II) complexes is of crucial importance toward understanding Pt interactions with cellular biomolecules. Post-treatment fluorescent labeling of functionalized Pt(II)-based agents using the bioorthogonal Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction has recently been reported as a promising approach. Here we describe an azide-functionalized Pt(II) complex, cis-[Pt(2-azidobutyl)amido-1,3-propanediamine)Cl2] (1), containing the cis geometry and difunctional reactivity of cisplatin, and present a comparative study with its previously described alkyne-functionalized congener. Single-crystal X-ray diffraction reveals a dramatic change in the solid-state arrangement with exchange of the alkyne for an azide moiety wherein 1 is dominated by a pseudo-chain of Pt-Pt dimers and antiparallel alignment of the azide substituents, in comparison with a circular arrangement supported by CH/p(C=C) interactions in the alkyne version. In vitro studies indicate similar DNA binding and click reactivity of both congeners observed by fluorescent labeling. Interestingly, complex 1 shows in vitro enhanced click reactivity in comparison to a previously reported azide-appended Pt(II) complex. Despite their similar behavior in vitro, preliminary in cellulo HeLa studies indicate a superior imaging potential of azide-functionalized 1. Post-treatment fluorescent labeling of 1 observed by confocal fluorescence microscopy shows nuclear and intense nucleolar localization. These results demonstrate the potential of 1 in different cell line localization studies and for future isolation and purification of Pt-bound targets. [ABSTRACT FROM AUTHOR]

Protonated nitroarginine, [R + H], which contains the nitroguanidine 'explosophore,' undergoes homolytic N - N nitro-imine bond cleavage to expel NO and form a radical cation of arginine in high yield (100 % relative abundance) upon low-energy collision-induced dissociation (CID). Other ionization states of nitroarginine, including [R - H], and a fixed-charge derivative of nitroarginine do not expel NO (<1 %), but instead dissociate via heterolytic bond cleavage with abundant losses of small molecules (NO and HNO) from the nitroguanidine group. The effects of proton mobility on the CID reactions of nitroarginine containing peptides was investigated for peptide derivatives of leucine enkephalin, including XYGGFLR, X = D, G, K, and R, by examining the different protonation states: [M - H]; [M + H]; and [M + 2H]. For [M + H] containing the less basic N-terminal residues (X = D, G) and all [M + 2H], mobile proton fragmentation reactions that result in peptide sequence ions dominate. In contrast, for peptides containing the basic N-terminal residues (R and K), the CID spectra of both the [M - H] and [M + H] are dominated by the losses of small even-electron neutrals from the nitroarginine side-chain. The fraction of nitroguanidine directed fragmentation of the nitroarginine side chain that results in bond homolysis to form [XYGGFLR] by expulsion of NO increases by more than 10 times as the protonation state changes from [M - H] (<10 %) to [M + 2H] ( ca. 90 %) and by about four times as the acidity of the [M + H] N-terminal residue increases from R (19.0 %) to D (76.5 %). These results indicate that protonated peptides containing nitroarginine can undergo non-canonical mobile proton triggered radical fragmentation. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Despite the broad use of platinum-based chemotherapeutics, identification of their full range of cellular targets remains a significant challenge. In order to identify, visualize, and isolate cellular targets of Pt(II) complexes, we have modified the chemotherapeutic drug picoplatin with an azide moiety for subsequent click reactivity. The new compound picazoplatin readily binds DNA and RNA oligonucleotides and undergoes facile post-labeling click reactions to alkyne-fluorophore conjugates. Pt-fluorophore click reactions in rRNA purified from drug-treated Saccharomyces cerevisiae demonstrate its potential for future in vivo efforts. [ABSTRACT FROM AUTHOR]

The first structural characterization of a mononuclear, EPR-active, oxosulfido-Mo(V) compound related to the very rapid form of xanthine oxidase (VR-XnO) is reported. The compound, [CoCp2][TpiPrMoVOS(2-OC6H4CO2Et)] [Cp = cyclopentadienyl; TpiPr = hydrotris(3-isopropylpyrazol-1-yl)borate], exhibits a distorted octahedral geometry with Mo=O and Mo=S distances of 1.761(5) and 2.215(2) Å, respectively, and an O=Mo=S angle of 107.33(14)°. Significantly, the MoV=S distance is much shorter than the value of 2.36 Å reported for oxosulfido-Mo(V) compounds (Singh, R.; et al. Inorg. Chem. 1989, 28, 8) but close to the range established for VR-XnO by protein crystallography. The methyl and phenyl esters were also prepared but the latter is highly reactive and undergoes an intramolecular, radical-based cyclization/elimination reaction to form [CoCp2][TpiPrMoIVO{2-OC6H4C(O)S-κO,κS}]. This study provides the first definitive measurement of the MoVS bond distance in an unambiguously characterized oxosulfido-Mo(V) compound and supports the presence of a short (ca. 2.22 Å) Mo=S bond in VR-XnO. It also demonstrates that the MoV=S moiety participates in radical-based reactions that are facilitated by the facile redox interplay of Mo and S and by substrates susceptible to radical eliminations. [ABSTRACT FROM AUTHOR]

The first X-ray structures of two anomeric N,N-dialkoxyamides (2 and 3) have been obtained, which confirm that they are highly pyramidalized at nitrogen and have long N-CO bonds, a characteristic of other anomeric amides and a consequence of drastically reduced amidicity. The crystals also demonstrate chirality at the amide nitrogen in the solid state. The structures are well-predicted by density functional calculations using N,N-dimethoxyacetamide as a model. The amidicity of N,N-dimethoxyacetamide has been estimated by two independent methods, COSNAR and a new transamidation method, which give almost identical resonance stabilization energies of -8.6 kcal mol-1 and only 47% that of N,N-dimethylacetamide computed at the same level. The total destabilization is composed of a resonance and an inductive contribution, which we have evaluated separately. The electronegative oxygens at nitrogen are responsible for localization of the nitrogen lone pair on the amide nitrogen, a factor that contributes to a loss of resonance over and above the impact of pyramidalization at nitrogen, as well as the fact that N,N-dimethoxyacetamide is predicted to protonate on the carbonyl oxygen in preference to nitrogen. [ABSTRACT FROM AUTHOR]

Palladium-mediated hydrostannylation of alkynoyl compounds is combined with Stille-Scott cross-coupling (reductive-coupling) to give one-pot access to divinyl and aryl vinyl ketones, which undergo Nazarov cyclization to give cyclopentenones upon treatment with acid. This reaction sequence has been studied with a variety of different substitution patterns, including the use of oxazolidinone auxiliaries to achieve torquoselectivity in the Nazarov cyclization. Through a combination of good yields and moderate to good levels of stereochemical induction, this approach affords efficient, convergent, and asymmetric access to a variety of different cyclopentanoid systems. [ABSTRACT FROM AUTHOR]

A computational and X-ray crystallographic investigation of the electronic and geometric structures of a range of sulfonyl (—SO2—) and phosphonyl (—PO2-—) containing species was undertaken to investigate the nature of valency and bonding in these functional groups. The traditional representation of sulfonyl and phosphonyl species is with octet-violating Lewis structures, which require d-orbital participation at the central atom. However, computational studies cast serious doubt upon this bonding model. In this work, we have employed NBO/NRT analysis to investigate hybridization, atomic formal charges, donor—acceptor interactions, and resonance structure contributions. Our results predict that within sulfonyl and phosphonyl systems, bonding interactions are highly polarized, of the form X+—Y (X = P, S), and possess additional contributions from reciprocal n →σ* interactions where substituents off sulfur or phosphorus simultaneously act as donors and acceptors. Experimental evidence for the proposed bonding arrangement is provided for the sulfonyl functional group through a series of low-temperature X-ray structure correlations for sulfate monoesters, sulfamates, and methanesulfonates. Examination of changes to bond lengths and geometries upon substituent variation support the computational results. Together, our studies lend support for a bonding network in sulfonyl and phosphonyl groups composed of polar interactions augmented with reciprocal hyperconjugative bonding, which does not necessitate significant d-orbital participation nor formal octet violation at the central sulfur or phosphorus. [ABSTRACT FROM AUTHOR]

An investigation of the use of Cp2Zr(H)Cl (Schwart'z s reagent) to reduce a variety of amides to the corresponding aldehydes under very mild reaction conditions and in high yields is reported. A range of tertiary amides, including Weinreb's amides, can be converted directly to the corresponding aldehydes with remarkable chemoselectivity. Primary and secondary amides proved to be viable substrates for reduction as well, although the yields were somewhat diminished as compared to the corresponding tertiary amides Results from NMR experiments suggested the presence of a stable 18-electron zirconacycle intermediate that presumably affords the aldehyde upon water or silica gel workup A series of competition experiments revealed a preference of the reagent for substrates in which3 the lone pair of the nitrogen is electron releasing and thus more delocalized across the amide bond by resonance This trend accounts for the observed excellent selectivity for tertiary amides versus esters. Experiments regarding the solvent dependence of the reaction suggested a kinetic profile similar to that postulated for the hydrozirconation of alkenes and alkynes. Addition of p-anisidine to the reaction intermediate resulted in the formation of the corresponding imine mimicking the addition of water that forms the aldehyde. [ABSTRACT FROM AUTHOR]

The use of the Deoxo-Fluor reagent is a versatile method for acyl fluoride generation and subsequent one-flask amide coupling. It provides mild conditions and facile purification of the desired products in good to excellent yields. We have explored the utility of this reagent for the one-flask conversion of acids to amides and Weinreb amides and as a peptide-coupling reagent. [ABSTRACT FROM AUTHOR]

Presents x-ray structural studies on a series of oxygenated anthracene cycloadducts. Synthesis; Molecular structures; Bond distances and angles; Possible interactions involving C-OR sigma orbital; Calculated reaction coordinate for heterolysis of the C-OH[sup +][sub 2] bond.

Focuses on monomeric oxo dichloro 1,3-dialkyl p-tert-butylcalixarene complexes of molybdenum and tungsten. Unique tridentate; Collapsed calixarene unit; Potential as starting material for the expansion of group six calixarene chemistry.

The article presents a study regarding the enantioselective preparation of a stable boronate, complex in boron (B). It demonstrates that the racemic boron complex (R,S)-6 is appropriate for the analysis of X-ray crystallography. It notes that the conducted study is the first enantioselective synthesis to be performed on boron.

Reductive coupling of α,β-unsaturated acid chlorides A with alkynoyls B provides convergent access to Nazarov cyclization precursors, α-carboxy divinyl ketones C. Cyclization of C gives an intermediate oxyallyl cation intermediate D, which can be trapped with tethered arenes (Ar). The resultant products can be further cyclized through nucleophilic displacement of suitable leaving groups X by tethered OH groups to give lactones (in a subsequent step). Where X is a suitable chiral auxiliary (e.g., oxazolidinone) this strategy affords access to homochiral cyclopentanoids. [ABSTRACT FROM AUTHOR]

Thesynthesis of the C1–C18 fragment of the myxobacteriametabolite rhizopodin is described. Initial attempts at installingthe E,E-diene via cross couplingwith an oxazole fragment gave poor results. An alternative approach,in which the diene was formed prior and the oxazole introduced byan acylation/O,N-shift protocol, gave the C1–C18fragment 2of rhizopodin (1). [ABSTRACT FROM AUTHOR]

Indene-C70bisadduct (IC70BA) is a high performance electronacceptor material consisting of a mixture of regioisomers. A singleisomer of the IC70BA was isolated by careful chromatographicseparation. The structure of this isomer was confirmed by variousanalytical techniques including single crystal X-ray analysis. Theisomer showed superior performance to other isomer mixtures of IC70BA in bulk heterojunction solar cells using poly(3-hexylthiophene)as the donor material. [ABSTRACT FROM AUTHOR]

σC-C-σ*C-O interactions involving the strained carbon-carbon bonds of α- and β-nopinol, and their ester and ether derivatives have been demonstrated in the solid state using the variable oxygen probe. These hyperconjugative interactions are manifested as a strong response of the C-OR bond distance to the electron demand of the OR substituent. Although the effects upon the donor C-C bond distances are not large enough to be measurable by X-ray crystallography, they do result in systematic and measurable effects on the 13C-13C one-bond coupling constants. For the donor C-C bond, coupling constants decrease, consistent with weakening of this bond, while the intervening C-C bond coupling constants increase, consistent with bond strengthening, as the electron demand of OR increases. [ABSTRACT FROM AUTHOR]

Heme peroxidases including myeloperoxidase (MPO) arereleased atsites of inflammation by activated leukocytes. MPO generates hypohalousacids (HOX, X = Cl, Br, SCN) from H2O2; theseoxidants are bactericidal and are key components of the inflammatoryresponse. However, excessive, misplaced or mistimed production canresult in host tissue damage, with this implicated in multiple inflammatorydiseases. We report here methods for the conversion of simple monosaccharidesugars into selenium- and sulfur-containing species that may act aspotent water-soluble scavengers of HOX. Competition kinetic studiesshow that the seleno species react with HOCl with rate constants inthe range 0.8–1.0 × 108M–1s–1, only marginally slower than those for themost susceptible biological targets including the endogenous antioxidant,glutathione. The rate constants for the corresponding sulfur-sugarsare considerably slower (1.4–1.9 × 106M–1s–1). Rate constants for reactionof the seleno-sugars with HOBr are ∼8 times lower than thosefor HOCl (1.0–1.5 × 107M–1s–1). These values show little variation withdiffering sugar structures. Reaction with HOSCN is slower (∼102M–1s–1). The seleno-sugarsdecreased the extent of HOCl-mediated oxidation of Met, His, Trp,Lys, and Tyr residues, and 3-chlorotyrosine formation, on both isolatedbovine serum albumin and human plasma proteins, at concentrationsas low as 50 μM. These studies demonstrate that novel selenium(and to a lesser extent, sulfur) derivatives of monosaccharides couldbe potent modulators of peroxidase-mediated damage at sites of acuteand chronic inflammation, and in multiple human pathologies. [ABSTRACT FROM AUTHOR]

The reaction of MoVIO2(L-NS2) [L-NS2 = 2,6-bis(2,2-diphenyl-2-thioethyl)pyridinate(2-)] or MoV2O3(L-NS2)2 with excess PPh3 in N,N-dimethylformamide at 70 °C results in the formation of gray-green (L-NOS)MoIV(¼-O)((¼-S)MoIV(L-NS2) [L-NOS = 2(¼(2,2-diphenyl-2-thioethyl)-6-(2,2-diphenyl-2-oxoethyl)pyridinate(2-)] (1). The crystal structure of 1 revealed a dinuclear complex comprised of two trigonal bipyramidal Mo centers bridged along an axial-equatorial edge (the ¼-O-(¼-S vector) such that the MoN bonds are trans to the bridging atoms and are anti with respect to the MoMo bond (d(MoMo) = 2.5535(5) Å); the remaining coordination sites are occupied by the S- and O-donor atoms of the L-NOS and L-NS2 ligands. The diamond core is asymmetric, with Mo(1/2)-O(1) distances of 1.845(2) and 2.009(2) Å and Mo(1/2)-S(1) distances of 2.374(1) and 2.230(1) Å. Compound 1 is unique in possessing a planar, diamond-core unit devoid of terminal oxo ligation and a new tridentate L-NOS ligand formed via a novel intramolecular modification of the original L-NS2 ligand. [ABSTRACT FROM AUTHOR]

The early stages of the retro-Diels-Alder reaction are clearly apparent in the structures of the cycloadducts formed between furan or 5-trimethylsilylcyclopentadiene with maleic anhydride and N-methylmaleimide. The degree of lengthening of the C-C bonds that break in this reaction is clearly related to the known reactivity of these cycloadducts toward this reaction. In the structures of the cycloadducts 21 and 22 derived from 2-methoxyfuran, the early stages of an alternative fragmentation reaction are apparent, consistent with the reactivity of these compounds in solution. [ABSTRACT FROM AUTHOR]

N-Methyl-2-trialkylsilylmethylpyridinium cations 6a-c and 4-trialkylsilylmethylpyridinium cations 5a-e were prepared and investigated using 29Si and 13C NMR and single-crystal X-ray crystallography. Systematic differences in the 29Si chemical shifts and 29Si-13C one-bond coupling constants for these cations suggested that the Si-CH2 bond interacts more strongly at the 2-position of the electron-deficient pyridinium ring than at the 4-position. This result is supported by the X-ray structures of the pyridinium cations 5b and 6b.y [ABSTRACT FROM AUTHOR]

Presents the findings of a study which suggests that there is a small but significant C-O bond lengthening observed in the gamma-Si or Sn cyclohexyl esters, relative to the corresponding nonmetalated derivatives. Effect of group 4 metal substituents on positive charge at the beta position; Relative rates unimolecular solvolysis of the beta-trimethylmetal-substituted esters.

A series of four perylene diimide (PDI) chromophores were prepared with increasing steric bulk on the imide substituents with the aim of retarding the effect of concentration quenching on photoluminescence, commonly observed with these dyes. Spectroscopic investigations of the compounds in dilute solution confirmed that the photophysical properties of the PDI core chromophore were not perturbed by the bulky substituents. Solid film samples containing the PDI compounds at various concentrations dispersed in a poly(methyl methacrylate) (PMMA) matrix were examined and compared to amorphous neat films as well as crystalline samples. The PDI compounds containing di-tert-butylphenyl (bPDI-3) and trityl (bPDI-4) substituents showed near unity photoluminescence quantum yield (PLQY) up to 20 mM in PMMA compared to 10% PLQY for the reference compound (bPDI-1) without molecular insulation. Surprisingly, high concentrations (>40 mM) of a phenyl-substituted PDI compound (bPDI-2) with moderate molecular insulation formed emissive aggregates that showed a higher PLQY compared to the PDI derivatives with greater steric bulk. By examining the molecular structure and solid state packing in conjunction with a series of photophysical measurements, new insights into designing highly fluorescent dyes, particularly in the solid state, were obtained. The trityl-substituted PDI compound (bPDI-4) was used in a luminescent solar concentrator with optical quantum efficiency of 54%, flux gain of 6.4, and geometric gain of 45. [ABSTRACT FROM AUTHOR]

Achieving ready-enantioselective access to multistereocenter-containing cyclopentyl rings is an area of great significance to organic synthesis. In this work, we describe a general protocol for accessing multistereocenter-containing cyclopentanoids from simple N-alkynyloxazolidinones (Ox-ynamides). This protocol involves conversion of Ox-ynamides into Ox-activated divinyl and aryl vinyl ketones that undergo facile Nazarov cyclization with excellent chemo-, regio-, and stereocontrol. The Ox auxiliary directs all aspects of reactivity and selectivity, both in the electrocyclization and in the subsequent transformations of the resulting oxyallyl intermediate. Stereoinduction in the electrocyclization results from a "coupled-torque" mechanism in which rotation of the Ox group, driven by increasing orbital overlap of the nitrogen lone pair with the incipient oxyallyl cation, is coupled with the rotation of the termini of the pentadienyl cation, favoring a particular direction of conrotatory ring closure (torquoselectivity). The associated lone-pair stabilization of the transition state by Ox promotes cyclization of traditionally resistant substrates, broadening the scope of this asymmetric Nazarov cyclization. The Ox group also facilitates the stereo- and regioselective incorporation of nucleophiles (Nu) and dienes, giving more complex, multistereocenter containing cyclopentanoids. Finally, the Ox group is readily removed and recovered or can be converted into other amine functionalities. [ABSTRACT FROM AUTHOR]

An approach to the dihydrooxepino[4,3-b]pyrrole core of diketopiperazine natural products which utilizes a vinyl pyrrole epoxide Cope rearrangement was investigated. It was found that an ester substituent on the epoxide was essential for the [3,3]-rearrangement to occur. Density functional calculations with M06-2X provided explanations for the effects of the pyrrole and ester groups on these rearrangements. [ABSTRACT FROM AUTHOR]

The intramolecular Diels-Alder reaction has been used as a powerful method to access the tricyclic core of the eunicellin natural products from a number of 9-membered-ring precursors. The endo/exo selectivity of this reaction can be controlled through a remarkable organocatalytic approach, employing MacMillan's imidazolidinone catalysts, although the mechanistic origin of this selectivity remains unclear. We present a combined experimental and density functional theory investigation, providing insight into the effects of medium-ring constraints on the organocatalyzed intramolecular Diels-Alder reaction to form the isobenzofuran core of the eunicellins. [ABSTRACT FROM AUTHOR]

The intracellular distribution of fluorescently labeled copper and zinc bis(thiosemicarbazonato) complexes was investigated in M17 neuroblastoma cells and primary cortical neurons with a view to providing insights into the neuroprotective activity of a copper bis(thiosemicarbazonato) complex known as CuII(atsm). Time-resolved fluorescence measurements allowed the identification of the CuII and ZnII complexes as well as the free ligand inside the cells by virtue of the distinct fluorescence lifetime of each species. Confocal fluorescent microscopy of cells treated with the fluorescent copper(II)bis(thiosemicarbazonato) complex revealed significant fluorescence associated with cytoplasmic puncta that were identified to be lysosomes in primary cortical neurons and both lipid droplets and lysosomes in M17 neuroblastoma cells. Fluorescence lifetime imaging microscopy confirmed that the fluorescence signal emanating from the lipid droplets could be attributed to the copper(II) complex but also that some degree of loss of the metal ion led to diffuse cytosolic fluorescence that could be attributed to the metal-free ligand. The accumulation of the copper(II) complex in lipid droplets could be relevant to the neuroprotective activity of CuII(atsm) in models of amyotrophic lateral sclerosis and Parkinson’s disease. [ABSTRACT FROM AUTHOR]

With the aim of preparing hypoxia-selective imaging and therapeutic agents, technetium(I) and rhenium(I) tricarbonyl complexes with pyridylhydrazone, dipyridylamine, and pyridylaminocarboxylate ligands containing nitrobenzyl or nitroimidazole functional groups have been prepared. The rhenium tricarbonyl complexes were synthesized with short reaction times using microwave irradiation. Rhenium tricarbonyl complexes with deprotonated p-nitrophenyl pyridylhydrazone ligands are luminescent, and this has been used to track their uptake in HeLa cells using confocal fluorescent microscopy. Selected rhenium tricarbonyl complexes displayed higher uptake in hypoxic cells when compared to normoxic cells. A 99mTc tricarbonyl complex with a dipyridylamine ligand bearing a nitroimidazole functional group is stable in human serum and was shown to localize in a human renal cell carcinoma (RCC; SK-RC-52) tumor in a mouse. [ABSTRACT FROM AUTHOR]

SoftX-ray photoelectron spectroscopy has been used to investigatethe radiosensitizer nimorazole and related model compounds. We reportthe valence and C, N, and O 1s photoemission spectra and K-edge NEXAFSspectra of gas-phase nimorazole, 1-methyl-5-nitroimidazole, and 4(5)-nitroimidazolein combination with theoretical calculations. The valence band andcore level spectra are in agreement with theory. We determine theequilibrium populations of the two tautomers in 4(5)-nitroimidazoleand find a ratio of 1:0.7 at 390 K. The NEXAFS spectra of the studiednitroimidazoles show excellent agreement with spectra of compoundsavailable in the literature that exhibit a similar chemical environment.By comparing 1-methyl-5-nitroimidazole (single tautomer) with 4(5)-nitroimidazole,we are able to disentangle the photoemission and photoabsorption spectraand identify features due to each single tautomer. [ABSTRACT FROM AUTHOR]

Reaction of TpiPrMoVIOS(OAr) with cobaltocene in toluene results in the precipitation of brown, microcrystalline oxosulfido-Mo(V) compounds, [CoCp2][TpiPrMoVOS(OAr)] (Cp- = έ5-C5H5-, TpiPr- = hydrotris(3-isopropylpyrazol-1-yl)borate, OAr- = phenolate or 2-sBu, 2-tBu, 3-tBu, 4-sBu, 4-Ph, 3,5-sBu2, 2-CO2Me, 2-CO2Et or 2-CO2Ph derivative thereof). The compounds are air- and water-sensitive and display ν(Mo-O) and ν(Mo-S) IR absorption bands at ca. 890 and 435 cm-1, respectively, 20-40 cm-1 lower in energy than the corresponding bands in TpiPrMoOS(OAr). They are electrochemically active and exhibit three reversible cyclovoltammetric waves (E(MoVI/MoV) = -0.40 to -0.66 V, E([CoCp2]+/CoCp2) = -0.94 V and E(CoCp2/[CoCp2]-) = -1.88 V vs SCE). Structural characterization of [CoCp2][TpiPrMoOS(OC6H4CO2Et-2)]·2CH2Cl2 revealed a distorted octahedral Mo(V) anion with Mo-O and Mo-S distances of 1.761(5) and 2.215(2) Å, respectively, longer than corresponding distances in related TpiPrMoOS(OAr) compounds. The observation of strong S(1s) → (S(3p) + Mo(4d)) S K-preedge transitions indicative of a d¹ sulfido-Mo(V) moiety and the presence of short Mo-O (ca. 1.72 Å) and Mo-S (ca. 2.25 Å) backscattering contributions in the Mo K-edge EXAFS further support the oxosulfido-Mo(V) formulation. The compounds are EPR-active, exhibiting highly anisotropic (Δg 0.124-0.150), rhombic, frozen-glass spectra with g1 close to the value observed for the free electron (ge = 2.0023). Spectroscopic studies are consistent with the presence of a highly covalent Mo-S π* singly occupied molecular orbital. The compounds are highly reactive, with reactions localized at the terminal sulfido ligand. For example, the compounds react with cyanide and PPh3 to produce thiocyanate and SPPh3, respectively, and various (depending on solvent) oxo-Mo(V) species. Reactions with copper reagents also generally lead to desulfurization and the formation of oxo-Mo(V) or -Mo(IV) complexes. [ABSTRACT FROM AUTHOR]

Gas-phase carbon-carbon bond forming reactions, catalyzed by group 10 metal acetate cations [(phen)M(O2CCH3)]+ (where M = Ni, Pd or Pt) formed via electrospray ionization of metal acetate complexes [(phen)M(O2CCH3)2], were examined using an ion trap mass spectrometer and density functional theory (DFT) calculations. In step 1 of the catalytic cycle, collision induced dissociation (CID) of [(phen)M(O2CCH3)]+ yields the organometallic complex, [(phen)M(CH3)]+, via decarboxylation. [(phen)M(CH3)]+ reacts with allyl acetate via three competing reactions, with reactivity orders (% reaction efficiencies) established via kinetic modeling. In step 2a, allylic alkylation occurs to give 1-butene and reform metal acetate, [(phen)M(O2CCH3)]+, with Ni (36%) > Pd (28%) > Pt (2%). Adduct formation, [(phen)M(C6H11O2)]+, occurs with Pt (24%) > Pd (21%) > Ni(11%). The major losses upon CID on the adduct, [(phen)M(C6H11O2)]+, are 1-butene for M = Ni and Pd and methane for Pt. Loss of methane only occurs for Pt (10%) to give [(phen)Pt(C5H7O2)]+. The sequences of steps 1 and 2a close a catalytic cycle for decarboxylative carbon-carbon bond coupling. DFT calculations suggest that carbon-carbon bond formation occurs via alkene insertion as the initial step for all three metals, without involving higher oxidation states for the metal centers. [ABSTRACT FROM AUTHOR]

The article provides information on a study that reported on the synthesis and characterization of the first molybdenum-copper carbon monoxide dehydrogenase complexes. The study stated that a unique heterobimetallic Mo/Cu active site is present in the carbon monoxide dehydrogenase from Oligotropha carboxidovorans. This enzyme catalyzes the oxidation of carbon oxide and carbon dioxide. Some of the experiments done regarding the paramagnetic active site models indicated that few mechanisms invoke the direct participation of the sulfido ligand in the formation of thiocarbonate intermediates.

A bis(diphenylphosphino)methane-ligated trinuclear silver hydride nanocluster, [Ag3((Ph2P)2CH2)3(μ3-H)](BF4)2, featuring three silver(I) ions coordinated to a μ3-hydride, and its deuteride analogue, [Ag3((Ph2P)2CH2)3(μ3-D)](BF4)2, have been isolated and structurally characterized using electrospray ionization mass spectrometry (ESI-MS), X-ray crystallography, NMR and IR spectroscopy. The position of the deuteride in [Ag3((Ph2P)2CH2)3(μ3-D)](BF4)2 was determined by neutron diffraction. ESI-MS of [Ag3L3(μ3-H/D)](BF4)2 [L = ((Ph2P)2CH2)2] produces [Ag3L3(μ3-H/D)]2+ and [Ag3L3(μ3-H/D)(BF4)]+. A rich gas-phase ion chemistry of [Ag3L3(μ3-H/D)]2+ is observed under conditions of collision-induced dissociation (CID) and electron-capture dissociation (ECD). CID gives rise to the following complementary ion pairs: [Ag3L2]+ and [L+(H/D)]+; [Ag2(H/D)L2]+ and [AgL]+; [Ag2(H/D)L]+ and [AgL2]+. ECD gives rise to a number of dissociation channels including loss of the bis(phosphine) ligand, fragmentation of a coordinated bis(phosphine) ligand via C-P bond activation, and loss of a hydrogen (deuterium) atom with concomitant formation of [Ag3L3]+. Under CID conditions, [Ag3L3(μ3-H/D)(BF4)]+ fragments via ligand loss, the combined loss of a ligand and [H,B,F4], and cluster fragmentation to give [Ag2(BF4)L2]+ and [Ag2(L-H)L]+ [where (L-H) =(Ph2P)2CH-]. [ABSTRACT FROM AUTHOR]

The synthesis and characterization of a silver complex of the tripodal triazole ligand, tris(benzyltriazolylmethyl)amine (TBTA, L¹), that is used as promoter to enhance CuI-catalyzed azide-alkyne cycloaddition (CuAAC) reactions is reported. X-ray analysis of the silver(I) complex with L¹ reveals a dinuclear cation, [Ag2(L¹)2]2+, that is essentially isostructural to the copper(I) analogue. While the [Ag2(L¹)2](BF4)2 complex provides catalysis for the azide-alkyne cycloaddition process, evidence is presented that this arises from trace copper contamination. The synthesis of silver(I), copper(II), and copper(I) complexes of a second tripodal ligand, tris(2-benzimidazolymethyl)amine (L²), which is used to enhance the rate of CuAAC reactions, is also reported. X-ray crystallography of the CuI complex [Cu3I(L²)2(CH3CN)2](BF4)3 offers structural insight into previous mechanistic speculation about the role of this ligand in the CuAAC reaction. [ABSTRACT FROM AUTHOR]

One of the pathological hallmarks of Alzheimer's disease is the presence of amyloid-β plaques in the brain and the major constituent of these plaques is aggregated amyloid-β peptide. New thiosemicarbazone-pyridylhydrazine based ligands that incorporate functional groups designed to bind amyloid-β plaques have been synthesized. The new ligands form stable four coordinate complexes with a positron-emitting radioactive isotope of copper, 64Cu. Two of the new CuII complexes include a functionalized styrylpyridine group and these complexes bind to amyloid-β plaques in samples of post-mortem human brain tissue. Strategies to increase brain uptake by functional group manipulation have led to a 64Cu complex that effectively crosses the blood-brain barrier in wild-type mice. The new complexes described in this manuscript provide insight into strategies to deliver metal complexes to amyloid-β plaques. [ABSTRACT FROM AUTHOR]

An efficient, formal enantioselective synthesis of (+)- and (−)-pauciflorol F has been achieved using a recently introduced oxazolidinone controlled torquoselective Nazarov reaction. The absolute stereochemistry of pauciflorol F and its biosynthetic precursors has been unambiguously confirmed using X-ray crystallography. [ABSTRACT FROM AUTHOR]

5,5'-Disubstituted-3,3'-bisisoxazoles are prepared in one step by the dropwise addition of aqueous potassium hydrogen carbonate to a mixture of dichloroglyoxime and terminal alkynes. The reaction exhibits a striking preference for the 5,5'-disubstituted 3,3'-bisisoxazole over the 4,5'-regioisomer. Organometallic iridium and rhenium bisisoxazole complexes are luminescent with emission wavelengths varying depending upon the identity of the 5,5'-substituent (phenyl, butyl). [ABSTRACT FROM AUTHOR]

The benzoxyl radical is a key intermediate in the combustion of toluene and other aromatic hydrocarbons, yet relatively little experimental work has been performed on this species. Here, a combination of electrospray ionization (ESI), multistage mass spectrometry experiments, and density functional theory (DFT) calculations are used to examine the formation and fragmentation of a benzoxyl (benzyloxyl) distonic radical anion. Excited 4-carboxylatobenzoxyl radical anions were produced via two methods: (1) collision induced dissociation (CID) of the nitrate ester 4-(nitrooxymethyl)benzoate, OCCHCHONO, and (2) reaction of ozone with the 4-carboxylatobenzyl radical anion, OCCHCH. In neither case was the stabilized OCCHCHO radical anion intermediate detected. Instead, dissociation products at m/ z 121 and 149 were observed. These products are attributed to benzaldehyde (OCCHCHO) and benzene (OCCH) products from respective loss of H and HCO radicals in the vibrationally excited benzoxyl intermediate. In no experiments was a product at m/ z 120 (i.e., OCCH) detected, corresponding to absence of the commonly assumed phenyl radical + CH=O channel. The results reported suggest that distonic ions are useful surrogates for reactive intermediates formed in combustion chemistry. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Oxazolidinones are powerful promoters of the Nazarov reaction, enabling the cyclization of conventionally resistant substrates to be achieved under mild conditions. They exert excellent regio- and torquoselective control in both the conventional Nazarov reaction giving cyclopentenones and in the “interrupted” Nazarov reaction, giving more highly substituted multistereocenter containing products. [ABSTRACT FROM AUTHOR]

A series of novel 2-amino-3-benzoylthiophenes (2A3BTs)were screenedusing a functional assay of A1R mediated phosphorylationof extracellular signal-regulated kinases 1 and 2 (ERK1/2) in intactCHO cells to identify potential agonistic effects as well as the abilityto allosterically modulate the activity of the orthosteric agonist, R-PIA. Two derivatives, 8hand 8i, differing only in terms of the absence or presence of an electron-withdrawinggroup on the benzoyl moiety of the 2A3BT scaffold, were identifiedas biased allosteric agonists and positive allosteric modulators ofagonist function at the adenosine A1receptor (A1R) in two different functional assays. Our findings indicate thatsubtle structural variations can promote functionally distinct receptorconformational states. [ABSTRACT FROM AUTHOR]

The synthesis of new cage amine macrobicyclic ligands with pendent carboxylate functional groups designed for application in copper radiopharmaceuticals is described. Reaction of [Cu((NH2)2sar)]2+ (sar = 3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane) with either succinic or glutaric anhydride results in selective acylation of the primary amine atoms of [Cu((NH2)2sar)]2+ to give derivatives with either one or two aliphatic carboxylate functional groups separated from the cage amine framework by either a four- or five-atom linker. The CuII serves to protect the secondary amine nitrogen atoms from acylation, and can be removed to give the free ligands. The newly appended carboxylate functional groups can be used as sites of attachment for cancer-targeting peptides such as Lys3-bombesin. The synthesis of the first dimeric sarcophagine-peptide conjugate, possessing two Lys3-bombesin peptides tethered to a single cage amine, is presented. This species has been radiolabeled with copper-64 at ambient temperature and there is minimal dissociation of CuII from the conjugate even after two days of incubation in human serum. [ABSTRACT FROM AUTHOR]

Sky-blue Tp*WOCl2 has been synthesized from the high-yielding reaction of Tp*WO2Cl with boron trichloride in refluxing toluene. Dark-red Tp*WOI2 was prepared via thermal decarbonylation followed by aerial oxidation of Tp*WI(CO)3 in acetonitrile. From these precursors, an extensive series of mononuclear tungstenyl complexes, Tp*WOXY [X = C-, Y = OPh-, SPh-; X = Y = OPh-, 2-(n-propyl)pheno1ate (PP-), SPh-, SePh; XY = toluene-3,4-dithiolate (tdt2-), quinoxaline-2,3-dithiolate (qdt2-), benzene-1,2-diselenolate (bds2-); Tp* = hydrotris(3,5-dimethylpyrazol-l-yl)borate], was prepared by metathesis with the respective alkali-metal salt of X-/XY2- or (NHEt3)2(qdt). The complexes were characterized by microanalysis, mass spectrometry, electrochemistry, IR, electron paramagnetic resonance (EPR), and electronic absorption spectroscopies, and X-ray crystallography (for X Y = OPh-, PP-, SPh-; XY = bds²). The six-coordinate, distorted-octahedral tungsten centers are coordinated by terminal oxo [W≡O = 1.689(6)-1.704(3) Å], tridentate Tp*, and monodentate or bidentate O/S/Se-donor ligands. Spin Hamiltonian parameters derived from the simulation of fluid-solution X-band EPRspectra revealed that the soft-donor S/Se ligand complexes had largerg values and smaller 183W hyperfine coupling constants than the less covalent hard-donor O/Cl species. The former showed low-energy ligand-to-metal charge-transfer bands in the near-IR region of their electronic absorption spectra. These oxotungsten(V) complexes display lower reduction potentials than their molybdenum counterparts, underscoring the preference of tungsten for higher oxidation states. Furthermore, the protonation of the pyrazine nitrogen atoms of the qdt2- ligand has been examined by spectroelectrochemistry; the product of the one-electron reduction of [Tp*WO(qdtH)]+ revealed usually intense low-energy bands. [ABSTRACT FROM AUTHOR]

Trimer, tetramer, and pentamer oligomers based on the polymer backbone structure of poly[2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylenevinylene] (MEHPPV) have been synthesized by Horner-Wadsworth-Emmons reactions. The fluorescence spectra, emission quantum yields, and lifetimes of the oligomers have been characterized in dilute chloroform solutions. The oligomers exhibit a sequential increase in absorption and emission wavelength maxima and a decrease in fluorescence lifetime as the p conjugation length is increased. The shortening in excited state lifetime is shown to be due to an increase in the rates of both radiative and nonradiative processes. The absence of a mirror-image relationship for the absorption and fluorescence spectra of the oligomers is attributed to the photoexcitation of a range of torsional configurations followed by relaxation to a more planar arrangement that then emits. [ABSTRACT FROM AUTHOR]

Computational, solution phase, and crystal structure analysis of 2- and 4-organoselenylmethyl-substituted pyridinium ions (10a-c and 11a-c) provides strong evidence for C-Se hyperconjugation (σC-Se-π*) between the C-Se σ-bond and the π-deficient aromatic ring and a through-space interaction (nSe-π*) between the selenium p-type lone pair and the π-deficient aromatic ring. There is also a weak anomeric-type interaction (nSe-σ*CC) involving the selenium p-type lone pair electrons and the polarized CH2-C(Ar) σ-bond. NBO analysis of calculated cations with varying electron demand (B3LYP/6-311++G**) show that C-Se hyperconjugation (σC-Se-π*) is the predominant mode of stabilization in the weakly electron-demanding pyridinium ions (10d, 11d, 14, and 15); however, the through-space (nSe-π*) interaction becomes more important as the electron demand of the β-Se-substituted carbocation increases. The anomeric interaction (nSe-σ*CC) is relatively weak in all ions. [ABSTRACT FROM AUTHOR]

New bifunctional derivatives of diacetyl-bis(4-methylthiosemicarbazone) (H2atsm) have been prepared by a selective transamination reaction of a new dissymmetric bis(thiosemicarbazone) precursor H2L1. The new derivatives contain an aliphatic carboxylic acid (H2L2 and H2L3), t-butyl carbamale (H2L4), or ammonium ion (H2L5) functional group. The new ligands and copper(ll) complexes have been charactezed by NMR spectroscopy, mass spectromelry, and microanalysis. The complex CuII(L4) was structurally characterized by X-ray crystallography and shows the metal center to be in an N2S2 distorted square planar coordination geometry. Electrochemical measurements show that the copper(ll) complexes undergo a reversible reduction attributable to a Cu(ll)/Cu(l) process. The ligands and the copper(ll) complexes featuring a carboxylic acid functional group have been conjugated to the tumor targeting peptide bombesin(7-14)-NH2. The bifunctional peptide conjugates were radiolabeled with copper-64 in the interest of developing new positron emission tomography (PET) imaging agents. The conjugates were radiolabeled with copper- 64 rapidly in high radiochemical purity (>95%) at room temperature under mild conditions and were stable in a cysteine and histidine challenge study. [ABSTRACT FROM AUTHOR]

Green/blue Tp[sup/Pr]rMoO(S[sub2]PR[sub2]) (Tp[sup/Pr] = hydrotris(3-isopropylpyrazolyl)borate; R Pr[supi], Ph, OEt, OPr[supi], (-)-mentholate) complexes were synthesized and characterized by elemental analysis, mass spectrometry, IR and NMR spectroscopy, and X-ray crystallography. The diamagnetic, six-coordinate, oxo-Mo(IV) complexes possess distorted octahedral geometries defined by terminal oxo, bidentate dithio acid, and tridentate Tp ligands. The R = Pr[supi] and Ph derivatives are isomers of previously reported 1,2-borotropically shifted complexes, Tp[sup/Pr*]MoO(S[sub2]PR[sub2]) (Tp[sup/Pr*] = hydrobis(3-isopropylpyrazolyl)(5-isopropylpyrazolyl)borate; ref: Inorg. Chem. 1996, 35, 5368). Conversion of Tp[sup/Pr]MoO(S2PPh2) into Tp[sup/Pr*]MoO(S[sub2]PPh[sub2]) at elevated temperatures (>80 °C) showed that the borotropically shifted isomer was thermodynamically more stable than the unshifted species. Reaction with methanol converts Tp[sup/Pr]MoO(S[sub2]PPr[supi][sub2]) into (HB(OMe)(Prsupi]pz)[sub2])MoO(S[sub2]PPr[supi]) (Pr[supi]pz = 3-isopropylpyrazolyl), which was characterized by spectroscopic and crystallographic methods. [ABSTRACT FROM AUTHOR]

The Alder-Rickert ethylene extrusion reaction manifests in the ground state structures of compounds 9-12 which contain the bicyclo[2.2.2]octadiene moiety and compounds 13, 14, and 17-20 which contain the bicyclo[2.2.2]octene moiety. A significant decrease of the 13C-13C one-bond coupling constants for the C-C bonds, which break in this fragmentation reaction, suggests lengthening, and hence weakening of these bonds. In the unsymmetrical systems these effects are also shown to be associated with strengthening of the CH2-CH2 bond, which is ultimately lost from the molecule as ethylene. Low-temperature crystal structures of compounds 9-12 and 16 provide evidence for similar crystal packing requirements of the CH2-CH2 and CHCH moieties. [ABSTRACT FROM AUTHOR]

Brown TpiPrMoO(SR)(CO) (TpiPr = hydrotris(3-isopropylpyrazol-1-yl)borate; R = Et, iPr, Ph, p-tol, Bz) are formed when TpiPrMoO(SR)(NCMe) react with CO gas in toluene. The carbonyloxomolybdenum(IV) complexes exhibit ν(CO) and ν(Mo=O) IR bands at ca. 2025 and 935 cm-1, respectively, and NMR spectra indicative of C1 symmetry, with δC(CO) ca. 250. The crystal structure of TpiPrMoO(SiPr)(CO), the first for a mononuclear carbonyloxomolybdenum complex, revealed a distorted octahedral geometry, with d(Mo=O) = 1.683(3) Å, d(Mo-C) = 2.043(5) Å, and ∠(O=Mo-C) = 90.87(16)°. The blue-green acetonitrile precursors are generated by reacting cis-TpiPrMoO2(SR) with PPh3; they are unstable, display a single ν(Mo=O) IR band at ca. 950 cm-1, and exhibit NMR spectra consistent with C1 symmetry. Red-brown cis-TpiPrMoO2((SR) (R = as above and tBu) are formed by metathesis of TpiPrMoO2Cl and HSR/NEt3 in dichloromethane. The complexes exhibit strong ν(Mo02) IR bands at ca. 925 and 895 cm-1, and NMR spectra indicative of Cs symmetry; the isopropyl, p-tolyl, and benzyl derivatives possess distorted octahedral geometries, with d(Mo=O)av = 1.698 Å, and Z(MoO2)av = 103.5°. [ABSTRACT FROM AUTHOR]

Atom transfer reactions have been employed to convert Tp/PrMoO2(OAr) into monomeric cis- oxosulfido-Mo(VI) and dimeric y-disulfido-Mo(V) species, [Tp/PrrMoOS(OAr)]n (Tp/Pr = hydrotris(3-isopropyl- pyrazol-1 -yl)borate; OAr = phenolate or naphtholate derivative; n = 1 and 2, respectively). Dark red, monomeric Tp/PrMoOS(OAr) complexes contain distorted octahedral cis-oxosulfido-Mo(VI) centers, with d(Mo=O) = 1.692(5) Å, d(Mo=S) = 2.132(2) Å, and ∠(O=Mo=S) = 103.68(16)° for the 2-sec-butylphenolate derivative. Dark red-purple, dimeric [Tp/PrMoOS(OAr)]2 complexes undergo S–S bond cleavage forming monomeric oxosulfido-Mo(VI) species in solution. In the solid state, the 3,5-di-tert- butylphenolate derivative exhibits a centrosymmetric structure, with distorted octahedral anti oxo-Mo(V) centers bridged by a disulfido-κS,κS' ligand. Hydrolysis of the oxosulfido-Mo(VI) complexes results in the formation of [Tp/PrMoO]2(μ-S2)(μ-O). In anaerobic solutions, certain oxosulfido-Mo(Vl) complexes convert to molybdenyl complexes bearing bidentate 2-mercaptophenolate or related naphtholate ligands formed via intramolecular attack of the sulfido ligand on a coligand C-H group. The oxosulfido-Mo(Vl) complexes serve as precursors to biologically relevant Mo(V) and heterobimetallic MoO(μ-S)Cu species and undergo a range of biomimetic reactions. [ABSTRACT FROM AUTHOR]

A novel free radical trapping reaction based on a stepwise radical reversible addition-fragmentation mechanism has been utilized to synthesize a series of acenaphthenyl dimers and trimers. The synthetic procedure involves the reaction of acenaphthylene with dithiobenzoate compounds (S= C(Ph)-SR) in the presence of a free radical initiator followed by reduction of the dithiobenzoyl end group with tributyltin hydride. Stereoisomers of the compounds have been isolated and their structures determined by proton NMR and X-ray crystallography. The solution fluorescence of the compounds has been characterized to reveal the requirements for intramolecular excimer (excited-state dimer) formation. Only in compounds containing identical stereochemical arrangements of adjacent acenaphthenyl groups is excimer fluorescence observed following photoexcitation. [ABSTRACT FROM AUTHOR]