This preliminary investigation of the octadentate acyclic chelator H(4)octapa (N(4)O(4)) with (111)In/(115)In(3+) has demonstrated it to be an improvement on the shortcomings of the current industry "gold standards" DOTA (N(4)O(4)) and DTPA (N(3)O(5)). The ability of H(4)octapa to radiolabel quantitatively (111)InCl(3) at ambient temperature in 10 min with specific activities as high as 2.3 mCi/nmol (97.5% radiochemical yield) is presented. In vitro mouse serum stability assays have demonstrated the (111)In complex of H(4)octapa to have improved stability when compared to DOTA and DTPA over 24 h. Mouse biodistribution studies have shown that the radiometal complex [(111)In(octapa)](-) has exceptionally high in vivo stability over 24 h with improved clearance and stability compared to [(111)In(DOTA)](-), demonstrated by lower uptake in the kidneys, liver, and spleen at 24 h. (1)H/(13)C NMR studies of the [In(octapa)](-) complex revealed a 7-coordinate solution structure, which forms a single isomer and exhibits no observable fluxional behavior at ambient temperature, an improvement to the multiple isomers formed by [In(DTPA)](2-) and [In(DOTA)](-) under the same conditions. Potentiometric titrations have determined the thermodynamic formation constant of the [In(octapa)](-) complex to be log K(ML) = 26.8(1). Through the same set of analyses, the [(111/115)In(decapa)](2-) complex was found to have nonoptimal stability, with H(5)decapa (N(5)O(5)) being more suitable for larger metal ions due to its higher potential denticity (e.g., lanthanides and actinides). Our initial investigations have revealed the acyclic chelator H(4)octapa to be a valuable alternative to the macrocycle DOTA for use with (111)In, and a significant improvement to the acyclic chelator DTPA.

The correlation between rapid initiation and rapid decomposition in olefin metathesis is probed for a series of fast-initiating, phosphine-free Ru catalysts: the Hoveyda catalyst HII, RuCl(L)(═CHCH- o-O Pr); the Grela catalyst nG (a derivative of HII with a nitro group para to OPr); the Piers catalyst PII, [RuCl(L)(═CHPCy)]OTf; the third-generation Grubbs catalyst GIII, RuCl(L)(py)(═CHPh); and dianiline catalyst DA, RuCl(L)( o-dianiline)(═CHPh), in all of which L = HIMes = N,N'-bis(mesityl)imidazolin-2-ylidene. Prior studies of ethylene metathesis have established that various Ru metathesis catalysts can decompose by β-elimination of propene from the metallacyclobutane intermediate RuCl(HIMes)(κ-CH), Ru-2. The present work demonstrates that in metathesis of terminal olefins, β-elimination yields only ca. 25-40% propenes for HII, nG, PII, or DA, and none for GIII. The discrepancy is attributed to competing decomposition via bimolecular coupling of methylidene intermediate RuCl(HIMes)(═CH), Ru-1. Direct evidence for methylidene coupling is presented, via the controlled decomposition of transiently stabilized adducts of Ru-1, RuCl(HIMes)L(═CH) (L = py ; n' = 1, 2, or o-dianiline). These adducts were synthesized by treating in situ-generated metallacyclobutane Ru-2 with pyridine or o-dianiline, and were isolated by precipitating at low temperature (-116 or -78 °C, respectively). On warming, both undergo methylidene coupling, liberating ethylene and forming RuCl(HIMes)L. A mechanism is proposed based on kinetic studies and molecular-level computational analysis. Bimolecular coupling emerges as an important contributor to the instability of Ru-1, and a potentially major pathway for decomposition of fast-initiating, phosphine-free metathesis catalysts.

A long-standing question in olefin metathesis centers on whether the "release−return" (boomerang) mechanism contributes to the productivity of Hoveyda-class catalysts. According to this mechanism, a molecule of oisopropoxystyrene (A) is liberated during catalyst initiation, but recaptures the active catalyst following metathesis. The relevance of this pathway for the second-generation Hoveyda catalyst HII was assessed in metathesis of 1,1-and 1,2disubstituted olefins. Crossover studies with 13 C-labeled A*, as well as competition experiments involving ring-closing or cross metathesis (RCM, CM) in the presence of A (equimolar with HII) indicated rapid reuptake of styrenyl ether. The crossover studies indicated highly efficient catalyst initiation, with the entire catalyst charge being activated before metathesis was complete. In a comparative study involving CM of anethole with methyl acrylate, sustained activity was shown for HII, whereas the secondgeneration Grubbs catalyst GII was rapidly deactivated. These data demonstrate that the release−return mechanism is indeed operative for HII in these demanding metathesis reactions, and that facile shuttling from a protected recapture cycle into the productive metathesis cycle contributes to the superior performance of HII relative to GII.

Brønsted bases of widely varying strength are shown to decompose the metathesis-active Ru intermediates formed by the second-generation Hoveyda and Grubbs catalysts. Major products, in addition to propenes, are base·HCl and olefin-bound, cyclometalated dimers [RuCl(κ-HIMes-H)(HC═CHR)] Ru-3. These are generated in ca. 90% yield on metathesis of methyl acrylate, styrene, or ethylene in the presence of either DBU, or enolates formed by nucleophilic attack of PCy on methyl acrylate. They also form, in lower proportions, on metathesis in the presence of the weaker base NEt. Labeling studies reveal that the initial site of catalyst deprotonation is not the HIMes ligand, as the cyclometalated structure of Ru-3 might suggest, but the metallacyclobutane (MCB) ring. Computational analysis supports the unexpected acidity of the MCB protons, even for the unsubstituted ring, and by implication, its overlooked role in decomposition of Ru metathesis catalysts.

The mechanism originally proposed by Fischer and Tropsch for carbon monoxide (CO) hydrogenative catenation involves CC coupling from a carbide-derived surface methylidene. A single molecular system capable of capturing these complex chemical steps is hitherto unknown. Herein, we demonstrate the sequential addition of proton and hydride to a terminal Mo carbide derived from CO. The resulting anionic methylidene couples with CO (1 atm.) at low-temperature (-78 °C) to release ethenone. Importantly, the synchronized delivery of two reducing equivalents and an electrophile, in the form of a hydride (H-= 2e-+ H +), promotes alkylidene formation from the carbyne precursor and enables coupling chemistry, under conditions milder than those previously described with strong one-electron reductants and electrophiles. Thermodynamic measurements bracket the hydricity and acidity requirements for promoting methylidene formation from carbide as energetically viable upon formal heterolysis of H2. Methylidene formation prior to CC coupling proves critical for organic product release, as evidenced by direct carbide carbonylation experiments. Spectroscopic studies, a monosilylated model system, and Quantum Mechanics computations provide insight into the mechanistic details of this reaction sequence, which serves as a rare model of the initial stages of the Fischer Tropsch synthesis.