Total Synthesis of (+)‐Rubriflordilactone A

Two enantioselective total syntheses of the nortriterpenoid natural product rubriflordilactone A are described, which use palladium‐ or cobalt‐catalyzed cyclizations to form the CDE rings, and converge on a late‐stage synthetic intermediate. These key processes are set up through the convergent coupling of a common diyne component with appropriate AB‐ring aldehydes, a strategy that sets the stage for the synthetic exploration of other members of this family of natural products.     

Bioactivity and chemical composition of the essential oil from the leaves of Guatteria australis A.St.-Hil

Essential oil from the leaves of Guatteria australis was obtained by hydrodistillation, analyzed by Gas Chromatography coupled to Mass Spectromery (GC–MS) and their antiproliferative, antileishmanial, antibacterial, antifungal and antioxidant activities were also evaluated. Twenty-three compounds were identified among which germacrene B (50.66%), germacrene D (22.22%) and (E)-caryophyllene (8.99%) were the main compounds. The highest antiproliferative activity was observed against NCI-ADR/RES (TGI = 31.08 μg/ml) and HT-29 (TGI = 32.81 μg/ml) cell lines. It also showed good antileishmanial activity against Leishmania infantum (IC₅₀ = 30.71 μg/ml). On the other hand, the oil exhibited a small effect against Staphylococcus aureus ATCC 6538, S. aureus ATCC 14458 and Escherichia coli ATCC 10799 (MIC = 250 μg/ml), as well as small antioxidant activity (457 μmol TE/g) assessed through ORAC_FL assay. These results represent the first report regarding chemical composition and bioactivity of G. australis essential oil.     

Protonation and Proton‐Coupled Electron Transfer at S‐Ligated [4Fe‐4S] Clusters

Biological [Fe‐S] clusters are increasingly recognized to undergo proton‐coupled electron transfer (PCET), but the site of protonation, mechanism, and role for PCET remains largely unknown. Here we explore this reactivity with synthetic model clusters. Protonation of the arylthiolate‐ligated [4Fe‐4S] cluster [Fe₄S₄(SAr)₄]^2? ( 1 , SAr=S‐2,4‐6‐(iPr)₃C₆H₂) leads to thiol dissociation, reversibly forming [Fe₄S₄(SAr)₃L]^1? ( 2 ) and ArSH (L=solvent, and/or conjugate base). Solutions of 2 +ArSH react with the nitroxyl radical TEMPO to give [Fe₄S₄(SAr)₄]^1? ( 1_ox ) and TEMPOH. This reaction involves PCET coupled to thiolate association and may proceed via the unobserved protonated cluster [Fe₄S₄(SAr)₃(HSAr)]^1? ( 1‐H ). Similar reactions with this and related clusters proceed comparably. An understanding of the PCET thermochemistry of this cluster system has been developed, encompassing three different redox levels and two protonation states.     

The Development of Appropriate Upscaling Procedures

Permeability upscaling should be carried out with careful attention to the nature of rock heterogeneities. While there are many large-scale features which must be taken into account, there are also important heterogeneities at the small-scale. Many sedimentary structures contain laminae at the mm–cm scale, and beds at the m-scale, which give rise to strong contrasts in permeability. We use a 2D model derived from a photo-panel of an aeolian outcrop, along with permeability measurements from a North Sea oil field, to demonstrate the effects of small-scale heterogeneity. This model is similar in size to a typical cell of a reservoir geological model. We take imaginary probe and core plug measurements from the model, average them, and compare these with the effective permeability for the model computed from a finite difference flow calculation. Although this procedure is standard practice, we show that it can lead to biased estimates of the permeabilities used in flow simulation. As an alternative we suggest using models of representative beds, and performing flow simulation to calculate effective permeabilities for both single-phase and two-phase flow.     

Thermal phase behavior of DMPG bilayers in aqueous dispersions as revealed by 2H- and 31P-NMR

The synthetic lipid 1,2-dimyristoyl-sn-3-phosphoglycerol (DMPG), when dispersed in water/NaCl exhibits a complex phase behavior caused by its almost unlimited swelling in excess water. Using deuterium ((2)H)- and phosphorus ((31)P)-NMR we have studied the molecular properties of DMPG/water/NaCl dispersions as a function of lipid and NaCl concentration. We have measured the order profile of the hydrophobic part of the lipid bilayer with deuterated DMPG while the orientation of the phosphoglycerol headgroup was deduced from the (31)P NMR chemical shielding anisotropy. At temperatures >30 °C we observe well-resolved (2)H- and (31)P NMR spectra not much different from other liquid crystalline bilayers. From the order profiles it is possible to deduce the average length of the flexible fatty acyl chain. Unusual spectra are obtained in the temperature interval of 20-25 °C, indicating one or several phase transitions. The most dramatic changes are seen at low lipid concentration and low ionic strength. Under these conditions and at 25 °C, the phosphoglycerol headgroup rotates into the hydrocarbon layer and the hydrocarbon chains show larger flexing motions than at higher temperatures. The orientation of the phosphoglycerol headgroup depends on the bilayer surface charge and correlates with the degree of dissociation of DMPG-Na(+). The larger the negative surface charge, the more the headgroup rotates toward the nonpolar region.     

Degradation kinetics of poly(lactic-co-glycolic) acid block copolymer cast films in phosphate buffer solution as revealed by infrared and Raman spectroscopies

Poly(lactic-co-glycolic) acid (PLGA) is an important copolymer used in drug delivery platforms where controlled release is required. In this work we investigated the in vitro degradation of four PLGA copolymers with L/G molar compositions of 50/50, 65/35, 75/25 and 95/5. ATR-IR and Raman spectroscopies were used to differentiate and quantify the degradation rates of glycolic and lactic units. Both techniques were used to determine the polymer composition as a function of degradation time and the degradation rate constants for the hydrolysis of glycolic and lactic units were calculated using a 1st order kinetics approach. Our results revealed a two stage process for the degradation of PLGA cast films in PBS in agreement with our previous work. The degradation rate constant for glycolic unit was found to be 1.3 times higher than for lactic units. In addition the degradation rate constants for L and G units were shown to decrease proportionally with increasing initial lactic content of the copolymer used to prepare the films.     

QTAIM analysis of the HF, HCl, HBr, and HOH elimination reactions of halohydrocarbons and halohydroalcohols

The 1,2-HX elimination reaction (where X = F, Cl, Br, OH) has been established as an important reaction in the degradation of compounds introduced into the upper atmosphere, including common CFC replacement compounds. By analyzing the electron densities of the transition state geometries of these reactions using QTAIM, we see that we can divide these reactions into two types. For HF and HOH elimination, the transition state is a complete ring of bonds, and neither the C-H nor the C-X bonds have been broken at the maximum of energy. There is very little accumulation of electron density on the X atom, with the majority of charge being lost by the hydrogen atom undergoing elimination, being transferred on to the two carbon atoms. In HCl and HBr elimination, a similar loss of electron density of the hydrogen atom is accompanied by significant accumulation of electron density on the X atom and a smaller change in electron density on the carbon atoms. The C-X bond is broken in the transition state geometry, with no ring critical point being present. This may explain the relative stabilities of halohydrocarbons and haloalcohols with respect to loss of H-X.