Terminal substituent effects on the reactivity, thermodynamics, and stereoselectivity of the 8π-6π electrocyclization cascades of 1,3,5,7-tetraenes.

M06-2X/6-31+G(d,p) computations are reported for the 8π-6π electrocyclization cascades of 1,3,5,7-tetraenes. The rate-determining step for these cascades is typically the second (6π) ring closure. According to experiment and theory, un- and monosubstituted tetraenes readily undergo 8π electrocyclic ring closure to form 1,3,5-cyclooctatrienes; however, the 6π electrocyclizations of these cyclooctatriene intermediates are slow and reversible, and mixtures of monocyclic and bicyclic products are formed. Computations indicate that di- and trisubstituted tetraenes undergo facile but less exergonic 8π electrocyclization due to a steric clash that destabilizes the 1,3,5-cyclooctatriene intermediates. Relief of this steric clash ensures the subsequent 6π ring closures of these intermediates are both kinetically facile and thermodynamically favorable, and only the bicyclic products are observed for the cascade reactions of naturally occurring tri- and tetrasubstituted tetraenes (in agreement with computations). The 6π electrocyclization step of these cascade electrocyclizations is also potentially diastereoselective, and di- and trisubstituted tetraenes often undergo cascade reactions with high diastereoselectivities. The exo mode of ring closure is favored for these 6π electrocyclizations due to a steric interaction that destabilizes the endo transition state. Thus, theory explains both the recalcitrance of the unsubstituted 1,3,5,7-octatetraene and 1-substituted tetraenes toward formation of the bicyclo[4.2.0]octa-2,4-diene products, as well as the ease and the stereoselectivity with which terminal di- and trisubstituted tetraenes are known to react biosynthetically

Vesicoscopic Ureteral Reimplantation: A Minimally Invasive Technique for the Definitive Repair of Vesicoureteral Reflux

The surgical treatment of vesicoureteral relfux can range from injection therapy to open ureteral reimplantation. Minimally invasive applications for treatment of vesicoureteral relfux include laparoscopic extravesical and intravesical ureteral reimplantation. We present our extended experience of the technique for intravesical cross-trigonal ureteral reimplantation for vesicoureteral relux

Part-per-billion measurement of the 42S1/2→32D5/24^2S_{1/2} \rightarrow 3^2D_{5/2} electric quadrupole transition isotope shifts between 42,44,48^{42,44,48}Ca+^+ and 40^{40}Ca+^+

We report a precise measurement of the isotope shifts in the $4^2$S$_{1/2} \rightarrow 3^2$D$_{5/2}$ electric quadrupole transition at 729~nm in the $^{40 - 42,44,48}$Ca$^+$. The measurement has been made via high-resolution laser spectroscopy of co-trapped ions, finding measured shifts of 2,771,872,467.6(7.6), 5,340,887,394.6(7.8), and 9,990,381,870.0(6.3) Hz between $^{42,44,48}$Ca$^+$and $^{40}$Ca$^+$, respectively. By exciting the two isotopes simultaneously using frequency sidebands derived from a single laser systematic uncertainties resulting from laser frequency drifts are eliminated. This permits far greater precision than similar previously published measurements in other alkaline-earth systems. The resulting measurement precision provides a benchmark for tests of theoretical isotope shift calculations, and also offers a step towards probing New Physics via isotope shift spectroscopy.Comment: 9 pages, 7 figure

Prescribing pattern of analgesics used for postoperative pain and its correlate with patient and doctor satisfaction:

Background: Post operative pain is difficult to assessment and its management has been neglected at times. Moreover, the drug treatment involves administration of drug on as and when basis which leads to inadequate control. Methods: This observational, prospective study was conducted in 100 post-operative patients i.e., 50 each from surgery and orthopedics departments. Investigator enrolled post-operative patients within 24 hours of surgery and followed them for next 5 days or till hospital discharge, whichever was earlier. Analgesic prescribing pattern, self-assessment of pain, patient and doctor satisfaction using ASSIST questionnaire were recorded in Case Record Form and analysed. Results: Out of 100 patients, average number of analgesics prescribed post-operatively was 1.49±0.5 (baseline and all follow-up). 76.5% patients received NSAIDs which included diclofenac (44.29%) and paracetamol (30.87%). Opioids in the form of tramadol were prescribed in 23.49% patients. Mean least pain experienced by patients on day 1 was 2±0.75 which decreased to 1.32±0.63 on day 5. Mean worst pain decreased from 6.64±1.43 on day 1 to 3.38±1.17 on day 5. Average percentage of duration of severe pain was 35.2%±16.48 on day 1 which successively decreased to 16.32±8.26 on day 5. Average pain relief observed in 62.3% patients on day one increased to 80.88% on day 5. Patient satisfaction increased as pain score decreased (r=-0.73) and a strong positive correlation was observed between doctor satisfaction and patient satisfaction (r=0.91). Conclusions: Inadequate control of post-operative pain affects effective patient management and recovery. Incorporation of effective pain assessment scores in pain management is desirable

Optical cycling in polyatomic molecules with complex hyperfine structure

We have developed and demonstrated a scheme to achieve rotationally-closed photon cycling in polyatomic molecules with complex hyperfine structure and sensitivity to hadronic symmetry violation, specifically $^{171}$YbOH and $^{173}$YbOH. We calculate rotational branching ratios for spontaneous decay and identify repumping schemes which use electro-optical modulators (EOMs) to address the hyperfine structure. We demonstrate our scheme by cycling photons in a molecular beam and verify that we have achieved rotationally-closed cycling by measuring optical pumping into unaddressed vibrational states. Our work makes progress along the path toward utilizing photon cycling for state preparation, readout, and laser cooling in precision measurements of polyatomic molecules with complex hyperfine structure.Comment: 10 pages, 7 figure

Part-per-billion measurement of the 4^2S_(1/2)→3^2D_(5/2) electric-quadrupole-transition isotope shifts between ^(42,44,48)Ca^+ and ^(40)Ca^+

We report a precise measurement of the isotope shifts in the 4^2S_(1/2)→3^2D_(5/2) electric quadrupole transition at 729 nm in ^(40−42,44,48)Ca^+. The measurement has been made via high-resolution laser spectroscopy of co-trapped ions, finding measured shifts of 2 771 872 467.6(7.6), 5 340 887 394.6(7.8), and 9 990 381 870.0(6.3) Hz between ^(42,44,48)Ca^+ and ^(40)Ca^+, respectively. By exciting the two isotopes simultaneously, using frequency sidebands derived from a single laser, systematic uncertainties resulting from laser frequency drifts are eliminated. This permits far greater precision than similar previously published measurements in other alkaline-earth-metal systems. The resulting measurement accuracy provides a benchmark for tests of theoretical isotope shift calculations and also offers a step towards probing new physics via isotope shift spectroscopy

Gating mechanism of elongating β-ketoacyl-ACP synthases.

Carbon-carbon bond forming reactions are essential transformations in natural product biosynthesis. During de novo fatty acid and polyketide biosynthesis, β-ketoacyl-acyl carrier protein (ACP) synthases (KS), catalyze this process via a decarboxylative Claisen-like condensation reaction. KSs must recognize multiple chemically distinct ACPs and choreograph a ping-pong mechanism, often in an iterative fashion. Here, we report crystal structures of substrate mimetic bearing ACPs in complex with the elongating KSs from Escherichia coli, FabF and FabB, in order to better understand the stereochemical features governing substrate discrimination by KSs. Complemented by molecular dynamics (MD) simulations and mutagenesis studies, these structures reveal conformational states accessed during KS catalysis. These data taken together support a gating mechanism that regulates acyl-ACP binding and substrate delivery to the KS active site. Two active site loops undergo large conformational excursions during this dynamic gating mechanism and are likely evolutionarily conserved features in elongating KSs

An unexpected Ireland–Claisen rearrangement cascade during the synthesis of the tricyclic core of Curcusone C: Mechanistic elucidation by trial-and-error and automatic artificial force-induced reaction (AFIR) computations

In the course of a total synthesis effort directed toward the natural product curcusone C, the Stoltz group discovered an unexpected thermal rearrangement of a divinylcyclopropane to the product of a formal Cope/1,3-sigmatropic shift sequence. Since the involvement of a thermally forbidden 1,3-shift seemed unlikely, theoretical studies involving two approaches, the “trial-and-error” testing of various conceivable mechanisms (Houk group) and an “automatic” approach using the Maeda–Morokuma AFIR method (Morokuma group) were applied to explore the mechanism. Eventually, both approaches converged on a cascade mechanism shown to have some partial literature precedent: Cope rearrangement/1,5-sigmatropic silyl shift/Claisen rearrangement/retro-Claisen rearrangement/1,5-sigmatropic silyl shift, comprising a quintet of five sequential thermally allowed pericyclic rearrangements