Aggregation and solubility behavior of asphaltenes and their subfractions

Asphaltenes from four different crude oils (Arab Heavy, B6, Canadon Seco, and Hondo) were fractionated in mixtures of heptane and toluene and analyzed chemically, by vapor pressure osmometry (VPO), and by small angle neutron scattering (SANS). Solubility profiles of the asphaltenes and their subfractions indicated strong cooperative asphaltene interactions of a particular subfraction that is polar and hydrogen bonding. This subfraction had lower H/C ratios and modestly higher N, V, Ni, and Fe contents than the less polar and more soluble subfraction of asphaltenes. VPO and SANS studies indicated that the less soluble subfractions formed aggregates that were considerably larger than the more soluble subfractions. In general, asphaltene aggregate size increased with decreasing solvent aromaticity up to the solubility limit, beyond which the aggregate size decreased with heptane addition. The presence of a low wavevector Q feature in the scattering curves at 25 degrees C indicated that the individual aggregates were flocculating; however, the intensity of the feature was diminished upon heating of the samples to 80 degrees C. The solubility mechanism for Canadon Seco asphaltenes, the largest aggregate formers, appears to be dominated by aromatic pi-bonding interactions due to their low H/C ratio and low nitrogen content. B6 and Hondo asphaltenes formed similar-sized aggregates in heptol and the solubility mechanism is most likely driven by polar interactions due to their relatively high H/C ratios and high nitrogen contents. Arab Heavy, the least polar asphaltene, had a H/C ratio similar to Canadon Seco but formed the smallest aggregates in heptol. The enhancement in polar and pi-bonding interactions for the less soluble subfraction indicated by elemental analysis is reflected by the aggregate size from SANS. The less soluble asphaltenes contribute the majority of species responsible for aggregation and likely cause many petroleum production problems such as pipeline deposition and water-in-oil emulsion stabilization.     

Origin of enantioselection in chiral alcohol oxidation catalyzed by Pd[(-)-sparteine]Cl2

A kinetic investigation into the origin of enantioselectivity for the Pd[(-)-sparteine]Cl(2)-catalyzed aerobic oxidative kinetic resolution (OKR) is reported. A mechanism to account for a newly discovered chloride dissociation from Pd[(-)-sparteine]Cl(2) prior to alcohol binding is proposed. The mechanism includes (1) chloride dissociation from Pd[(-)-sparteine]Cl(2) to form cationic Pd(-)-sparteine]Cl, (2) alcohol binding, (3) deprotonation of Pd-bound alcohol to form a Pd-alkoxide, and (4) beta-hydride elimination of Pd-alkoxide to form ketone product and a Pd-hydride. Utilizing the addition of (-)-sparteine HCl to control the [Cl(-)] and [H(+)] and the resulting derived rate law, the key microscopic kinetic and thermodynamic constants were extracted for each enantiomer of sec-phenethyl alcohol. These constants allow for the successful simulation of the oxidation rate in the presence of exogenous (-)-sparteine HCl. A rate law for oxidation of the racemic alcohol was derived that allows for the successful prediction of the experimentally measured k(rel) values when using the extracted constants. Besides a factor of 10 difference between the relative rates of beta-hydride elimination for the enantiomers, the main enhancement in enantiodetermination results from a concentration effect of (-)-sparteine HCl and the relative rates of reprotonation of the diastereomeric Pd-alkoxides.     

Reaction-based machine learning representations for predicting the enantioselectivity of organocatalysts

Hundreds of catalytic methods are developed each year to meet the demand for high-purity chiral compounds. The computational design of enantioselective organocatalysts remains a significant challenge, as catalysts are typically discovered through experimental screening. Recent advances in combining quantum chemical computations and machine learning (ML) hold great potential to propel the next leap forward in asymmetric catalysis. Within the context of quantum chemical machine learning (QML, or atomistic ML), the ML representations used to encode the three-dimensional structure of molecules and evaluate their similarity cannot easily capture the subtle energy differences that govern enantioselectivity. Here, we present a general strategy for improving molecular representations within an atomistic machine learning model to predict the DFT-computed enantiomeric excess of asymmetric propargylation organocatalysts solely from the structure of catalytic cycle intermediates. Mean absolute errors as low as 0.25 kcal mol⁻¹ were achieved in predictions of the activation energy with respect to DFT computations. By virtue of its design, this strategy is generalisable to other ML models, to experimental data and to any catalytic asymmetric reaction, enabling the rapid screening of structurally diverse organocatalysts from available structural information.

A machine learning model for enantioselectivity prediction using reaction-based molecular representations.     

A stereoselective synthesis of the C(1)-C(16) fragment of the bryostatins

A synthesis of the C(1)-C(16) fragment of the brysostatins has been developed. Key steps are the stereoselective copper(I) catalysed addition of allylmagnesium bromide to an alkynyl ester, a condensation of a βγ-unsaturated aldehyde with a ketophosphonate, and the formation of the B-ring under mild conditions by stereoselective intramolecular conjugate addition.     

Rearrangement of 5-trimethylsilylthebaine on treatment with L-selectride: an efficient synthesis of (+)-bractazonine

Treatment of 5-trimethylsilylthebaine with L-Selectride gave rise to a rearrangement to 10-trimethylsilylbractazonine through migration of the phenyl group, whereas treatment of thebaine with strong Lewis acids is known to lead to a similar rearrangement through migration of the alkyl bridge to give, after reduction, (+)-neodihydrothebaine. It is suggested that the rearrangement of the alkyl group of thebaine is favored due to the formation of a tertiary benzylic cation. However, for 5-trimethylsilylthebaine, the lithium ion of L-Selectride acts as the Lewis acid and the beta-silyl effect dominates in the stabilization of any positive charge. This rearrangement provides a clear example of the greater relative migratory aptitude of phenyl groups over alkyl groups, and provides an efficient synthesis of (+)-bractazonine from thebaine.     

Microwave-assisted "libraries from libraries" approach toward the synthesis of allyl- and C-cyclopropylalkylamides

Cascade reactions of internal and terminal alkynes, zirconocene hydrochloride, dimethylzinc, and phosphinoyl imines (prepared in one step from aldehydes and diphenylphosphinoyl amide) lead to allylic phosphinoyl amides after aqueous workup. Microwave acceleration allows the completion of this one-pot reaction sequence in 10 min. These allylic amides can be converted into a variety of derivatives, including carbamates and sulfonamides, or reacted prior to workup with diiodomethane to give novel C-cyclopropylalkylamides. A solution-phase "libraries from libraries" approach was used to generate an intermediate 20-member library which was subsequently expanded to a 100-member library by a series of N-functionalizations. The biological activity was evaluated in an assay for competitive binding to the estrogen receptor (ERalpha), revealing three potent lead compounds of a new structural type.     

Stereoselective association of binuclear metallacycles in coordination polymers

A series of structurally related binuclear metallacycles [Cd(NO(3))(2)L](2), where L is an angular exo-bidentate ligand, have been synthesized. Each metallacycle contains two coordinatively unsaturated, chiral metal centers within a single molecule, and the assembly of these metallacycles into polymeric framework structures has been studied systematically for the first time. Stereoselective homochiral association of [Cd(NO(3))(2)L](2) leads to the formation of helical coordination polymers, whereas meso type association results in nonhelical chain structures. The type of stereoselective aggregation depends on the conditions of self-assembly as well as on ligand functionality. Both helical and nonhelical polymeric complexes have been isolated for the metallacycle [Cd(NO(3))(2)(2,4'-pyacph)](2) (2,4'-pyacph = 2,4'-(4-ethynylphenyl)bipyridyl). Homochiral association results in the formation of helical [Cd(NO(3))]( infinity ) chains which link the binuclear [Cd(NO(3))(2)(2,4'-pyacph)](2) metallacycles into racemic two-dimensional sheets which contain both P and M [Cd(NO(3))]( infinity ) helices. In contrast, meso-association leads to the formation of nonhelical one-dimensional chains. It is shown that the product of homochiral association is predominately formed at room temperature and that of meso-association is generated at elevated temperatures. Thus, it may be concluded that the homochiral association appears to be energetically less favorable than the meso-association, a conclusion that has been confirmed by theoretical calculations of the crystal lattice energy. Several high-yield syntheses of bipyridyl-type ligands used for metallacyclic assembly are also reported.     

Adamantane-like cluster complexes of mixed-valent copper-copper and nickel-copper thiolates

Square-planar copper(II) and nickel(II) derivatives of the cis-dithiolate N(2)S(2) ligand bis(N,N'-2-mercapto-2-methylpropyl)-1,5-diazocyclooctane, (bme*daco)M, nucleate four Cu(I)Cl moieties, forming M(II)(2)Cu(I)(4)S(4) clusters with unusual triply bridging thiolates, mu(3)-SR, in the topological form of adamantane. As determined by X-ray crystallography, the (bme*daco)M (M = Cu or Ni) metallothiolate serves as a bidentate ligand that bridges four Cu(I) ions, utilizing all lone pairs on sulfurs. Further characterization by electrochemical and electronic spectral measurements suggests greater electron delocalization in the all-copper complex as compared to the NiCu heterometallic complex. Mass spectral data imply that the mixed-metal Ni(II)(2)Cu(I)(4)S(4) is more stable toward CuCl loss than Cu(II)(2)Cu(I)(4)S(4), a result that is corroborated by extraction of Cu(I) by 1,2-bis(diphenylphosphino)ethane in the latter but not the former.     

Syntheses and properties of related polyoxadiazoles and polytriazoles

New aromatic poly-1,2,4-triazoles and poly-1,3,4-oxadiazoles are studied as thermally stable membrane materials. Various groups were introduced onto the pendant phenyl groups of poly-1,2,4-triazoles. Glass transition temperature, degradation temperature, and cold crystallization behavior were studied as a function of these groups. Cold crystallization appeared to be highly sensitive to macromolecular regularity. The solubility of poly-1,3,4-oxadiazoles was highly improved upon incorporation of 5-t-butylisophthalic, 1,1,3-trimethyl-3-phenylindane, 4,4′-(2,2′-diphenyl) hexafluoro propane, and diphenyl ether groups into the polymeric main chain, whereas the high glass transition temperatures and degradation temperatures typical for aromatic poly-1,3,4-oxadiazoles were maintained. © 1994 John Wiley & Sons, Inc.     

Direct detection of oxygen intermediates in the non-heme Fe enzyme taurine/alpha-ketoglutarate dioxygenase

The reaction of substrate-bound taurine/alpha-ketoglutarate dioxygenase with O2 has been studied using cryogenic continuous-flow spectroscopy. Transient absorption spectra acquired at -38 degrees C show an exponential decay of a 318-nm chromophore with an apparent rate of 1.3 s-1. The observed optical changes and their kinetics are consistent with the profile of an Fe(IV) species detected recently by M?ssbauer spectroscopy (Price et al., Biochemistry 2003, 42, 7497-7508). Resonance Raman measurement upon excitation at 363.7 nm reveal at least two oxygen isotope-sensitive vibrations at 821/787 cm-1 and 583/555 cm-1 for 16O and 18O derivatives, respectively. An additional mode is likely to be obscured by an ethylene glycol vibration at 865 cm-1 and/or 1089 cm-1. The 821 cm-1 vibration is assigned to the stretching mode of Fe(IV)=O species on the basis of its frequency and isotopic shift amplitude. The 583 cm-1 band is likely to originate from an Fe-O2 precursor of the Fe(IV)=O species, although its structural details are unclear at present.