Photocatalytic Thiol-Yne Reactions of Alkynyl Sulfides.

Thiol-yne reactions typically employ thiols and terminal alkynes as the reaction partners. The thiol-yne reaction of alkynyl sulfides and thiols is possible when employing a nonmetal photocatalyst eosin Y, green LED irradiation, under an air atmosphere. Alkynyl sulfides were transformed in good overall yields (58-90% total yields, 11 examples) favoring the cis isomer. No addition to the α-position of the alkynyl sulfide is observed, and regioselectivity is believed to be controlled through the stabilization of radical intermediates by the adjacent sulfur atom. Furthermore, control experiments with "all-carbon" internal alkynes demonstrate that alkynyl sulfides possess improved reactivity and regioselectivity profiles during thiol-yne processes.

Heteroleptic Copper(I)-Based Complexes Incorporating BINAP and π-Extended Diimines: Synthesis, Catalysis and Biological Applications.

A series of copper-based photocatalysts of the type Cu(NN)(BINAP)BF4 were synthesized bearing π-extended diimine ligands. Their behavior in several photocatalytic processes were evaluated and revealed acceptable levels of activity in an SET process, but negligible activity in PCET or ET processes. Suitable activity in ET processes could be restored through modification of the ligand. The BINAP-derived complexes were then evaluated for activity against triple-negative breast cancer cell lines. Controls indicated that copper complexes, and not their ligands, were responsible for activity. Encouraging activity was displayed by a homoleptic complex Cu(dppz)2BF4.

Computational Insight into Cu-Catalyzed Csp-S Coupling to Form a Macrocyclic Alkynyl Sulfide.

Copper-catalyzed Csp-S cross-coupling is known to form rare macrocyclic alkynyl sulfides. Computational studies now suggest a mechanism for the reaction pathway. Upon formation of Cu-S species, subsequent α-addition/elimination at the ethynylic carbon affords the desired macrocycle.

Synthesis and Diversification of Macrocyclic Alkynediyl Sulfide Peptides.

The synthesis of rare macrocyclic alkynediyl sulfides by a Cu-catalyzed Csp -S cross-coupling is presented. The catalytic protocol (Cu(MeCN)4 PF6 /dtbbpy) promotes macrocyclization of peptides, dipeptides and tripeptides at ambient temperature (14 examples, 23→73 % yields) via thiols and bromoalkynes, and is chemoselective with regards to terminal alkynes. Importantly, the underexplored alkynediyl sulfide functionality incorporates a rigidifying structural element and opens new opportunities for diversification of macrocyclic frameworks through S oxidation, halide addition and azide-alkyne cycloaddition chemistries to integrate sulfones, halides or valuable fluorophores (7 examples, 37→92 % yields).

A synthetic guide to alkynyl sulfides.

The relative stability and predictable reactivity of alkynyl sulfides make them ideal synthons for the development of new transformations. Classic methods for forming alkynyl sulfides relied on dehydrohalogenation approaches. However more recent methods have focused on employing umpolung strategies, as well as nucleophilic and electrophilic thiol alkynylation. In addition, the recent syntheses of Csp-S bonds have trended towards exploiting catalysis and expanding the reaction scope of the methods. A survey of existing methods to form alkynyl sulfides is presented as well as an evaluation with regards to the scope of each method, to provide the reader with an overview of advantages and limitations of current technology.

Comparing Forced-Air to Resistive-Polymer Warming for Perioperative Temperature Management: A Retrospective Study.

PURPOSE: Compare perioperative temperature management between forced-air warming (FAW) and resistive-polymer heating blankets (RHBs). DESIGN: A retrospective, quasi-experimental study. METHODS: Retrospective data analysis of nonspine orthopedic cases (N = 426) over a one-year period including FAW (n = 119) and RHBs (n = 307). FINDINGS: FAW was associated with a significantly higher final intraoperative temperature (P = .001, d = 0.46) than the RHB. The incidence of hypothermia was not found to be significantly different at the end (P = .102) or anytime throughout surgery (P = .270). Of all patients who started hypothermic, the FAW group had a lower incidence of hypothermia at the end of surgery (P = .023). CONCLUSIONS: FAW was associated with higher final temperatures and a greater number of normothermic patients than RHBs. However, no causal relationship between a warming device and hypothermia incidence should be assumed.

Risk Factors for Perioperative Hypothermia: A Literature Review.

PURPOSE: The purpose of this article was to review the literature to identify risk factors for the development of unplanned perioperative hypothermia and to evaluate the strength of the evidence for each risk factor. DESIGN: Comprehensive literature review METHODS: An evidence rating scale was used to evaluate the strength and quality of the research gathered. FINDINGS: At this time, only anecdotal evidence is available to guide our efforts in the maintenance of perioperative normothermia. There is currently no strong evidence to implicate risk factors that do or do not cause a patient to develop unplanned perioperative hypothermia. CONCLUSIONS: It is crucial to prevention that health care providers are able to identify risk factors and implement interventions. However, vigilance in the perioperative period can only enhance patient safety when we know what to look for. More research is needed to identify risk factors of unplanned perioperative hypothermia and effectively maintain normothermia throughout the perioperative period.

Heteroleptic Copper(I)-Based Complexes for Photocatalysis: Combinatorial Assembly, Discovery, and Optimization.

A library of 50 copper-based complexes derived from bisphosphines and diamines was prepared and evaluated in three mechanistically distinct photocatalytic reactions. In all cases, a copper-based catalyst was identified to afford high yields, where new heteroleptic complexes derived from the bisphosphine BINAP displayed high efficiency across all reaction types. Importantly, the evaluation of the library of copper complexes revealed that even when photophysical data is available, it is not always possible to predict which catalyst structure will be efficient or inefficient in a given process, emphasizing the advantages for catalyst structures with high modularity and structural variability.

Photocatalyic Appel reaction enabled by copper-based complexes in continuous flow.

A copper-based photocatalyst, Cu(tmp)(BINAP)BF4, was found to be active in a photoredox Appel-type conversion of alcohols to bromides. The catalyst was identified from a screening of 50 complexes and promoted the transformation of primary and secondary alcohols to their corresponding bromides and carboxylic acids to their anhydrides. The protocol was also amendable and optimized under continuous flow conditions.

Heteroleptic Cu-Based Sensitizers in Photoredox Catalysis.

Photochemistry is an important tool in organic synthesis that has largely been underdeveloped in comparison to thermal activation. Recent advances in technology have ushered in a new era in synthetic photochemistry. The emergence of photocatalysis, which exploits sensitizers for the absorption of visible light, has provided organic chemists with a new route to the generation of radical intermediates for synthesis. Of particular interest is the development of Cu-based complexes for photocatalysis, which possess variable photophysical properties and can display complementary reactivity with common photocatalysts based on heavier transition metals such as Ru or Ir. Heteroleptic Cu-based sensitizers incorporating the presence of both a bisphosphine and diamine ligand bound to the copper center are a promising class of photocatalysts. Their synthesis is a single step, often involving only precipitation for purification. In addition, it was shown that the sensitizers could be formed in situ in the reaction mixture, simplifying the experimental setup. The heteroleptic nature of the Cu-complexes also affords opportunities to fine-tune properties. For example, structurally rigidified bisphosphines reinforce geometries about the metal center to extend the excited state lifetime. Variation of the diamine ligand can influence the excited state oxidation/reduction potentials and optical absorbances. The heteroleptic complex Cu(XantPhos)(neo)BF4 has demonstrated utility in the synthesis of helical polyaromatic carbocycles. The synthesis of [5]helicene, a relatively simple member of the helicene family, was improved from the existing UV-light mediated method by eliminating the formation of unwanted byproducts. In addition, the Cu-based sensitizers also promoted the formation of novel pyrene/helicene hybrids for materials science applications. The synthetic methods that were developed were augmented when combined with continuous flow technology. The irradiation of reaction mixtures as they are pumped through small diameter tubing provides a more homogeneous and increased photon flux compared with irradiation in round-bottom flasks or other batch reactors. The value of continuous flow methods is also evident when examining UV-light photochemistry, where the simple and safe experimental set-ups allow for further exploration of high energy light for synthetic purposes. The synthesis of functionalized complex carbazoles was also studied using both a visible light method exploiting a heteroleptic copper-based sensitizer and a UV-light mediated method. It was demonstrated that both the photocatalysis methods and UV light photochemistries were rendered more user-friendly, safe, and reproducible when using continuous flow methods. Interestingly, the two photochemical methods often afford contrasting selectivities as a result of their inherently different mechanisms. It can be expected that the complementarity of the various photochemical methods will be an asset to synthetic chemists as the field continues to evolve.

Phase Separation Macrocyclization in a Complex Pharmaceutical Setting: Application toward the Synthesis of Vaniprevir.

A phase separation/continuous flow strategy employing an oxidative Glaser-Hay coupling of alkynes has been applied toward the synthesis of the macrocyclic core of complex pharmaceutical vaniprevir. The phase separation/continuous flow strategy afforded similar yields at 100-500 times the concentration and at shorter reaction times than common slow addition/high dilution techniques. In addition, dendritic PEG cosolvents were employed in the phase separation strategy for the first time and shown to allow productive macrocyclization at concentrations up to 200 mM.

Photochemical Dual-Catalytic Synthesis of Alkynyl Sulfides.

A photochemical dual-catalytic cross-coupling to form alkynyl sulfides via C(sp)-S bond formation is described. The cross-coupling of thiols and bromoalkynes is promoted by a soluble organic carbazole-based photocatalyst using continuous flow techniques. Synthesis of alkynyl sulfides bearing a wide range of electronically and sterically diverse aromatic alkynes and thiols can be achieved in good to excellent yields (50-96 %). The simple continuous flow setup also allows for short reaction times (30 min) and high reproducibility on gram scale. In addition, we report the first application of photoredox/nickel dual catalysis towards macrocyclization, as well as the first example of the incorporation of an alkynyl sulfide functional group into a macrocyclic scaffold.

Catalytic Macrocyclization Strategies Using Continuous Flow: Formal Total Synthesis of Ivorenolide A.

A formal total synthesis of ivorenolide A has been accomplished employing a Z-selective olefin cross metathesis and a macrocyclic Glaser-Hay coupling as key steps. The macrocyclization protocol employed a phase separation/continuous flow manifold whose advantages include catalysis, fast reaction times, high concentrations, and facile scale-up.

Perianesthetic Considerations for the Breastfeeding Mother.

Breastfeeding has been shown to be beneficial in the development of infants, but sometimes, the breastfeeding mother may require anesthesia. It is important for perianesthesia caregivers to understand how the breastfed infant may be affected by the anesthetic medications received by the breastfeeding mother. This article reviews current literature on drug transfer into breast milk and specifically how anesthetic drugs may affect breastfed infants. The pharmacokinetics of drug transfer during lactation is described as well as considerations for perianesthesia providers when caring for breastfeeding patients. The results of this literature review provide evidence that there is little risk to the breastfed infant after the mother receives surgical anesthesia. However, the type of drug, the dosage, the timing of treatment, and the infant's age and health must be taken into consideration.

Thromboelastography: Clinical Application, Interpretation, and Transfusion Management.

The coagulation cascade is a dynamic process dependent on many factors. It involves interaction between primary hemostasis, platelet clot formation, secondary hemostasis, thrombin generation, and fibrinolysis. The assessment of this process is particularly important in the surgical patient to properly manage hemostatic issues. Traditionally, coagulation tests used to guide transfusion management have included platelet count, activated partial thromboplastin time, prothrombin time, international normalized ratio, and activated clotting time, among others. Although these tests provide the practitioner with valuable information, they lack the ability to measure platelet function. The ability to measure whole blood coagulation, including platelet function, and not just the number of platelets, can be critical when a healthcare provider is determining what products are appropriate for a particular patient during surgery. One possible solution to this deficit in traditional coagulation monitoring is thromboelastography. Thromboelastography provides a more complete picture of coagulation status, taking into account more factors involved in the clotting process, including platelet function and temperature.

Residual Neuromuscular Blockade.

This article provides an update on residual neuromuscular blockade for nurse anesthetists. The neuromuscular junction, pharmacology for producing and reversing neuromuscular blockade, monitoring sites and methods, and patient implications relating to incomplete reversal of neuromuscular blockade are reviewed. Overall recommendations include using multiple settings when employing a peripheral nerve stimulator for monitoring return of neuromuscular function and administering pharmacologic reversal when the train-of-four ratio is below 0.9.

Tranexamic Acid in Anesthetic Management of Surgical Procedures.

Blood loss during surgical procedures poses a grave risk to the patient, but transfusion is costly and associated with adverse outcomes. Antifibrinolytics, however, offer an economical and effective means of decreasing blood loss associated with surgical procedures. Tranexamic acid (TXA) is an antifibrinolytic that blocks lysine-binding sites of fibrinogen and fibrin, preventing the breakdown of existing clots. This journal course reviews extensive research demonstrating that antifibrinolytics such as TXA decrease blood loss and in some studies reduce allogeneic transfusion requirements. In addition, this journal course addresses concerns that use of antifibrinolytics increases embolic events, reviews research that demonstrates TXA does not increase the incidence of vascular occlusive events, and describes methods of TXA use in cardiac and orthopedic surgical procedures, neurosurgery, and obstetrics. The Certified Registered Nurse Anesthetist should consider the possibility, on a case-by-case basis, of using TXA in surgical procedures to reduce blood loss with minimal adverse effects.

Photochemical Synthesis of Complex Carbazoles: Evaluation of Electronic Effects in Both UV- and Visible-Light Methods in Continuous Flow.

An evaluation of both a visible-light- and UV-light-mediated synthesis of carbazoles from various triarylamines with differing electronic properties under continuous-flow conditions has been conducted. In general, triarylamines bearing electron-rich groups tend to produce higher yields than triarylamines possessing electron-withdrawing groups. The incorporation of nitrogen-based heterocycles, as well as halogen-containing arenes in carbazole skeletons, was well tolerated, and often synthetically useful complementarity was observed between the UV-light and visible-light (photoredox) methods.

Lipid Emulsion in Treatment of Local Anesthetic Toxicity.

Epidural, spinal, regional, local, and intravenous administration of local anesthetics (LAs) is a cornerstone of anesthetic practice. LA toxicity is a grave consequence that is of great significance to anesthesia providers. Outcomes of LA toxicity range from inconvenient symptoms such as tinnitus, twitching, and hypotension to seizures; cardiovascular or respiratory collapse; and death. Lipid emulsion has emerged as a potential "magic bullet" in treating LA toxicity. This literature review provides background information and proposed mechanisms of action for LAs and lipid emulsion as well as animal experiments and a case report that speak to the effectiveness of lipid emulsion in the face of LA toxicity.

Infection Associated With Single-Dose Dexamethasone for Prevention of Postoperative Nausea and Vomiting: A Literature Review.

Postoperative nausea and vomiting is one of the most common complications affecting surgical patients. The glucocorticoid dexamethasone is often used for the prevention of postoperative nausea and vomiting. This literature review seeks to summarize research related to the use of a single perioperative dose of dexamethasone for prophylactic treatment of postoperative nausea and vomiting and its impact on surgical healing. Although the majority of the literature reviewed found no association between single-dose intraoperative dexamethasone and an increase in surgical site infections, the need for a large-scale randomized controlled trial is consistently mentioned. Prudent clinicians should always use the most current evidence with their best clinical judgment when making medication decisions for their patients.