AMHB: (Anti)aromaticity-Modulated Hydrogen Bonding

This <i>in silico</i> survey shows that changes in the (anti)­aromatic character of π-conjugated heterocycles can be used to fine-tune their hydrogen (H-)­bond strengths. Upon H-bonding dimerization, the π-electrons of these rings can be polarized to reinforce or disrupt their (anti)­aromatic π-conjugated circuits (πCCs) and stabilize or destabilize the resulting H-bonded complexes. H-bonding interactions that enhance aromaticity or relieve antiaromaticity are fortified, whereas those that intensify antiaromaticity or disrupt aromaticity are weakened, relative to analogues lacking full π-circuits. Computed dissected nucleus-independent chemical shifts, NICS(1)_<i>zz</i>, reveal a uniform pattern and document changes in the magnetic (anti)­aromatic character of the heterocycles considered. Recognition of this (anti)­aromaticity-modulated H-bonding (AMHB) phenomenon offers insights into a range of fields from organocatalysis and self-assembly to pharmaceutical chemistry and molecular biology

Nucleophile-Assisted Alkene Activation: Olefins Alone Are Often Incompetent

Emerging work on organocatalytic enantioselective halocyclizations naturally draws on conditions where both new bonds must be formed under delicate control, the reaction regime where the concerted nature of the Ad_E3 mechanism is of greatest importance. Without assistance, many simple alkene substrates react slowly or not at all with conventional halenium donors under synthetically relevant reaction conditions. As demonstrated earlier by Shilov, Cambie, Williams, Fahey, and others, alkenes can undergo a concerted Ad_E3-type reaction via nucleophile participation, which sets the configuration of the newly created stereocenters at both ends in one step. Herein, we explore the modulation of alkene reactivity and halocyclization rates by nucleophile proximity and basicity, through detailed analyses of starting material spectroscopy, addition stereopreferences, isotope effects, and nucleophile–alkene interactions, all obtained in a context directly relevant to synthesis reaction conditions. The findings build on the prior work by highlighting the reactivity spectrum of halocyclizations from stepwise to concerted, and suggest strategies for design of new reactions. Alkene reactivity is seen to span the range from the often overgeneralized “sophomore textbook” image of stepwise electrophilic attack on the alkene and subsequent nucleophilic bond formation, to the nucleophile-assisted alkene activation (NAAA) cases where electron donation from the nucleophilic addition partner activates the alkene for electrophilic attack. By highlighting the factors that control reactivity across this range, this study suggests opportunities to explain and control stereo-, regio-, and organocatalytic chemistry in this important class of alkene additions

Nucleophile-Assisted Alkene Activation: Olefins Alone Are Often Incompetent

Emerging work on organocatalytic enantioselective halocyclizations naturally draws on conditions where both new bonds must be formed under delicate control, the reaction regime where the concerted nature of the Ad_E3 mechanism is of greatest importance. Without assistance, many simple alkene substrates react slowly or not at all with conventional halenium donors under synthetically relevant reaction conditions. As demonstrated earlier by Shilov, Cambie, Williams, Fahey, and others, alkenes can undergo a concerted Ad_E3-type reaction via nucleophile participation, which sets the configuration of the newly created stereocenters at both ends in one step. Herein, we explore the modulation of alkene reactivity and halocyclization rates by nucleophile proximity and basicity, through detailed analyses of starting material spectroscopy, addition stereopreferences, isotope effects, and nucleophile–alkene interactions, all obtained in a context directly relevant to synthesis reaction conditions. The findings build on the prior work by highlighting the reactivity spectrum of halocyclizations from stepwise to concerted, and suggest strategies for design of new reactions. Alkene reactivity is seen to span the range from the often overgeneralized “sophomore textbook” image of stepwise electrophilic attack on the alkene and subsequent nucleophilic bond formation, to the nucleophile-assisted alkene activation (NAAA) cases where electron donation from the nucleophilic addition partner activates the alkene for electrophilic attack. By highlighting the factors that control reactivity across this range, this study suggests opportunities to explain and control stereo-, regio-, and organocatalytic chemistry in this important class of alkene additions

Nucleophile-Assisted Alkene Activation: Olefins Alone Are Often Incompetent

Emerging work on organocatalytic enantioselective halocyclizations naturally draws on conditions where both new bonds must be formed under delicate control, the reaction regime where the concerted nature of the Ad_E3 mechanism is of greatest importance. Without assistance, many simple alkene substrates react slowly or not at all with conventional halenium donors under synthetically relevant reaction conditions. As demonstrated earlier by Shilov, Cambie, Williams, Fahey, and others, alkenes can undergo a concerted Ad_E3-type reaction via nucleophile participation, which sets the configuration of the newly created stereocenters at both ends in one step. Herein, we explore the modulation of alkene reactivity and halocyclization rates by nucleophile proximity and basicity, through detailed analyses of starting material spectroscopy, addition stereopreferences, isotope effects, and nucleophile–alkene interactions, all obtained in a context directly relevant to synthesis reaction conditions. The findings build on the prior work by highlighting the reactivity spectrum of halocyclizations from stepwise to concerted, and suggest strategies for design of new reactions. Alkene reactivity is seen to span the range from the often overgeneralized “sophomore textbook” image of stepwise electrophilic attack on the alkene and subsequent nucleophilic bond formation, to the nucleophile-assisted alkene activation (NAAA) cases where electron donation from the nucleophilic addition partner activates the alkene for electrophilic attack. By highlighting the factors that control reactivity across this range, this study suggests opportunities to explain and control stereo-, regio-, and organocatalytic chemistry in this important class of alkene additions

165 PAVM patients graded according to self-reported exercise tolerance.

<p>A) SaO₂ relationships. Error bars represent mean and standard deviation. Similar trends were observed for median and IQR (data not shown). B) Oxygen content, calculated by <i>SaO₂ x haemoglobin x 1.34/100</i>, where SaO₂ was expressed as a %, and 1.34mls is the amount of oxygen carried per gram of haemoglobin <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090777#pone.0090777-Pittman1" target="_blank">[1]</a>. Error bars represent mean and standard deviation, but a similar trend was observed for median and IQR (data not shown).</p

Dissecting the Stereocontrol Elements of a Catalytic Asymmetric Chlorolactonization: <i>Syn</i> Addition Obviates Bridging Chloronium

We report absolute and relative stereochemistry of addition in enantioselective chlorolactonizations of 4-phenyl-4-pentenoic acid and its related <i>t</i>-butyl ester, catalyzed by (DHQD)₂PHAL. Predominant <i>syn</i> addition of the chlorenium and the nucleophile across the olefin is observed. As shown by isotopic labeling, NMR spectroscopy, and derivative studies, the two new stereocenters formed by addition across the double bond are set independently and influenced by different factors. These findings suggest a stepwise process via an intermediate capable of lactone closure with either stereochemistry, in contradistinction to the more familiar scenario in which <i>anti</i> addition is dictated by a bridging chloronium ion intermediate

Demographics, and univariate associations with improvement in exercise capacity post embolisation for the 98 PAVM patients.

<p>Patients stratified into those reporting and not reporting improved exercise tolerance. N, number with stated variable; IQR, interquartile range. PAP, pulmonary artery pressure; emb., embolisation. *P values calculated by logistic regression, and shown in bold where <0.05: Key odds ratios (and 95% confidence intervals) were 0.71 (0.56, 0.92) for albumin; 1.12 (1.01, 1.24) for PAP(systolic); 1.31 (1.04, 1.65) for PAP (diastolic); and 1.18 (1.01, 1.40) for PAP (mean). Note inverse associations are indicated by odds ratios <1.</p

Substrate Controlled Regioselective Bromination of Acylated Pyrroles Using Tetrabutylammonium Tribromide (TBABr₃)

Electrophilic bromination of pyrroles bearing carbonyl substituents at C-2 typically results in a mixture of the 4- and 5-brominated species, generally favoring the 4-position. Herein, we describe a substrate-controlled regioselective bromination in which tetra-butyl ammonium tribromide (TBABr₃) reacts with pyrrole-2-carboxamide substrates to yield the 5-brominated species as the predominant (up to >10:1) product

Blood oxygen content pre and post embolisation.

<p>Post embolisation data were obtained at clinic follow up at a median of 7 months (range (2–24) months after the final embolisation. Shaded areas represent 95% confidence interval for quadratic regression line for all 52 patients with pre and post embolisation haemoglobin measurements (pseudo r² 0.44, p<0.0001). Open diamonds represent individuals with pre embolisation serum iron <4 µmol/L.</p

Changes in SaO₂, haemoglobin, and oxygen content following PAVM embolisation.

<p>Data are provided only where available at all comparative timepoints for stated variable: immediately pre embolisation (previous evening, or same morning); the morning following embolisation (“immediate post (day 1)”); and at late follow up (“late post”), which referred to the first post embolisation follow up clinic, 2–24 (median 7) months post final embolisation. Where several embolisations took place in a series (17 patients required two sessions and 3 required three sessions), data are only reported pre and post final embolisation. The day 1 arterial oxygen content was calculated using the day 1 SaO₂ and pre-embolisation haemoglobin. P values for three way comparisons were calculated by Friedman, except for two way pre post haemoglobin comparisons which were calculated by Mann Whitney. IQR, interquartile range. ns, non significant (exact figure not provided from Kruskal Walllis.)</p