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Research has been conducted on the second-order rate constants. These constants have been measured for the addition of amines to ketenes in acetonitrile solution via the laser flash photolysis technique.

Flash photolysis of 10-diazo-9(10H)-phenanthrenone in aqueous solution provided two successively formed transient species, producing fluorene-9-carboxylic acid. The transients were identified as fluorenylideneketene, produced from a photo-Wolff reaction. Bromine scavenging determined the rate of enolization of fluorene-0-carboxylic acid.

A study of isomerization rate profiles of 1H-indene-1-carboxylic acid to 1H-indene-3-carboxylic acid in dilute aqueous solutions reveals an enolization-reketonization reaction sequence. 1-carboxylic acid and 3-carboxylic acid have carbon acid acidity and keto-enol equilibrium constants of 9.35 and 11.69, and 7.26 and 9.6, respectively. The study uses H2PO4, (CH3)(3)CPO3H and HCO3 anions as buffers.

Flash photolytic production of phenylcyanoketene by a photo-Wolff reaction of alpha-cyano-alpha-diazoacetophenone after hydration of the ketene provided the enol of alpha-cyano-alpha-phenylatic acid as a short-lined transient species. Estimations of the rates of ketonisation of the enol in dilute hydrochloric acid solutions, acetic acid, biphosphate ion, tris(hydroxymethyl)methylamine and ammonia buffers provided a rate profile with turning points. The first and second acid ionization constants of the enol could be establish from this profile.

Unlike literature and studies coming from high-income or Western countries, the existing conducted on the Middle East and North Africa fail to draw a nearly complete image of the characteristics of passenger travel behaviors in the urban areas of the region. This gap necessitates a holistic review of the previous studies and comparing their results of those of the international findings. This paper summarizes the status of urban travel behavior studies on the MENA region under eight categories of socioeconomics, land use, perceptions and attitudes, urban sprawl, neighborhood design, public transportation use, active mobility, and new technologies and concepts. Descriptive literature review and desk research depicts both lack of research results or data and differences between the behaviors in the MENA region and the Western countries. Moreover, based on the background review, this paper provides a list of recommendations for having more sustainable mobility in the MENA region.

Kinetic studies of acid dissociation of N-(pentafluorophenyl)-2-phenylethynamine in aqueous solution reveal that the reaction has a pK(a) value of 10.28 and the acidifying effect is evaluated as 10 pK units. Flash photolysis of an aminocyclopropenone produces this ynamine and it undergoes isomerization to ketenimine in aqueous solutions. Kinetic isotopic studies help examine the isomerization reaction and determine rate constants for various steps.

This report describes mathematical relationships between step and cumulative process mass intensities (PMIs) for synthesis plans, and analogous parameters applied to E-factors. It is shown that both step E-factors and step PMIs are not additive for synthesis plans. It is also shown that a recursive calculation of cumulative PMIs from step PMIs is a rapid method of determining overall PMIs for synthesis plans, though cumulative PMIs are not sufficiently informative as step PMIs or step E-factors to identify bottlenecks in synthesis plans. Illustrations on the use of these metrics to track the material efficiency of published synthesis plans for the pharmaceutical, apixaban, are given as a template example. Advantages and disadvantages of each metric are discussed. A general algorithm to select the most promising candidate synthesis plans considered at the design stage for a given molecular target that most likely satisfy “green” material efficiency criteria is also presented.

This paper proposes a standardized format for the preparation of process green synthesis reports that can be applied to chemical syntheses of active pharmaceutical ingredients (APIs) of importance to the pharmaceutical industry. Such a report is comprised of the following eight sections: a synthesis scheme, a synthesis tree, radial pentagons and step E-factor breakdowns for each reaction step, a tabular summary of key material efficiency step and overall metrics for a synthesis plan, a mass process block diagram, an energy consumption audit based on heating and cooling reaction and auxiliary solvents, a summary of environmental and safety-hazard impacts based on organic solvent consumption using the Rowan solvent greenness index, and a cycle time process schedule. Illustrative examples of process green synthesis reports are given for the following pharmaceuticals: 5-HT2B and 5-HT7 receptors antagonist (Astellas Pharma), brivanib (Bristol-Myers Squibb), and orexin receptor agonist (Merck). Methods of ranking synthesis plans to a common target product are also discussed using 6 industrial synthesis plans of apixaban (Bristol-Myers Squibb) as a working example. The Borda count method is suggested as a facile and reliable computational method for ranking multiple synthesis plans to a common target product using the following 4 attributes obtained from a process green synthesis report: process mass intensity, mass of sacrificial reagents used per kg of product, input enthalpic energy for solvents, and Rowan solvent greenness index for organic solvents.

Purpose: Metformin has been the first-line treatment for type 2 diabetes mellitus as monotherapy or concomitantly with other glucose-lowering therapies due to its efficacy, safety, and affordability. Recent studies on the cardioprotective and renoprotective benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have influenced guidelines on diabetes management to consider these newer agents as alternative first-line therapies. This paper explores the literature supporting the use of these newer medications alone as a first-line agent in place of metformin., Methods: A review of citations from the most recent guidelines along with a literature search via PubMed was completed to review (1) what, historically, made metformin first-line (2) if newer agents' benefits remain when used without metformin (3) how newer agents compare against metformin when used without it., Results: Evaluation of the historical literature was completed to summarize the key findings that support metformin as a first-line therapy agent. Additionally, an assessment of the literature reveals that the benefits of these two newer classes are independent of concomitant metformin therapy. Finally, studies have demonstrated that these newer agents can be either non-inferior or sometimes superior to metformin when used as monotherapy., Conclusion: GLP-1 RA and SGLT-2i can be considered as first line monotherapies for select patients with high cardiovascular risks, renal disease, or weight loss requirements. However, pharmacoeconomic considerations along with lesser long-term safety outcomes should limit these agents' use in certain patients as the management of diabetes continues to transition towards shared-decision making., Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01406-6., Competing Interests: Conflict of interestAuthors do not have any conflicts of interests, financial or otherwise, related to this article., (© The Author(s) 2024.)

Glucagon-like peptide-1 receptor analogs (GLP-1 RAs) have been an innovative and instrumental drug class in the management of both type 2 diabetes and obesity. Tirzepatide is a novel agent that acts as an agonist for both GLP-1 receptors and gastric inhibitory polypeptide (GIP) receptors, another incretin that lowers glucose and appetite. Although previous studies showed a lack of therapeutic benefit for GIP agonists, current studies show that the glucose lowering and weight loss effects of tirzepatide are at least as effective as GLP-1 RAs with a similar adverse effect profile. Some studies, though not conclusive, predict that tirzepatide may in fact be more potent than GLP-1 RAs at reducing weight. A thorough review of the studies that led to tirzepatide's approval allows for comparisons between tirzepatide and GLP-1 RAs; it also allows for predictions of tirzepatide's eventual place in therapy - an agent used preferentially over GLP-1 RAs in patients with or without diabetes desiring to lose weight., (© 2023. The Author(s).)

Materials and Methods: A nested case-control study design was chosen. Subjects enrolled were adult male patients who had a circumcision between January 2010 and December 2020 at our university hospital, with a confirmed LSc diagnosis on pathology. Cases were matched with controls by age with a ratio of 1 : 1, all of whom were circumcised and had a negative pathology report. Data collection consisted of sociodemographic, behavioral, and past medical and familial history characteristics., Results: A total of 94 patients were enrolled. The mean age was 49.81 (±22.92) in the group of men with LSc. No significant differences in sociodemographic characteristics (age and BMI) were found between the two compared groups. Smoking cannot predict LSc as opposed to alcohol consumption, which we found to be a protective factor against the appearance of LSc ( p =0.027). Men with LSc had significantly higher rates of diabetes ( p =0.021) and hypertension ( p =0.004). No associations were found between LSc and the presenting chief complaints, family history of LSc, and past penile trauma., Conclusion: In this study, we were able to compare multiple variables between 47 circumcised patients diagnosed with LSc and a control group. We found that LSc patients showed higher rates of diabetes and hypertension. A potential protective effect of alcohol consumption is to be explored in future projects with bigger sample sizes and higher statistical powers., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Joey El Khoury et al.)

Home blood pressure monitoring (HBPM) is a convenient way to assess out-of-office blood pressure control and is recommended by numerous international guidelines to aid clinicians in the diagnosis and management of essential hypertension. Although available guidelines recommend the use of HBPM in patients receiving antihypertensive medication, their specific recommendations regarding optimal monitoring schedule, duration, and clinician interpretation of home blood pressure readings may differ among guidelines. Purpose : The purpose of this article is to review available international hypertension guideline recommendations related to the use of HBPM to improve hypertension control among patients receiving antihypertensive therapy. We also briefly highlight clinical trials that have shown improved blood pressure control using HBPM to intensify antihypertensive therapy and provide a practical guide for implementing HBPM to improve hypertension control. Results: Eleven international guidelines were identified and reviewed. In total, recommendations relating to which HBPM to use, number of measurements per day, and how to interpret home blood pressure values were largely in agreement among available guidelines. Conclusion: Clinicians recommending HBPM to their patients with hypertension should utilise a standardised HBPM protocol, based on available guideline recommendations.

This paper describes a sustainability index (SI) as a quantitative measure of "sustainability" applicable to synthesis plans based on the provenance of input materials and energy sources and the fate of output waste products. The index is computed as the root-mean-square average of the following four parameters: mass fraction of valorized inputs ( F VI ), mass fraction of valorized outputs ( F VO ), mass fraction of valorized target product ( F VP ), and input enthalpic energy fraction arising from renewable energy sources ( F RE ). Valorized input materials originate from renewable, recycled, or reclaimed sources. Valorized output materials are destined for recycling or reclaiming so that they may be used in the same or other chemical processes. Valorized target product refers to that portion of the target product that is actually used for its intended purpose. Renewable energy sources are defined as originating from hydroelectric, wind, solar, geothermal, and biomass sources. The computation of SI is illustrated for 22 synthesis plans of the high commodity flavour ingredient vanillin from biofermentation, chemical synthesis, and solvent extraction processes. In addition, these plans are compared and ranked according to Borda count and poset (partially ordered set) pairwise dominance analyses using the following attributes: process mass intensity (PMI), sacrificial reagent (SR) consumption, input enthalpic energy (IEE) consumption, Rowan solvent greenness index (RSGI), and sustainability index (SI)., (Copyright © 2020, Andraos; licensee Beilstein-Institut.)

A new way of developing novel synthesis strategies for the construction of monocyclic rings found in organic molecules is presented. The method is based on the visual application of integer partitioning to chemical structures. Two problems are addressed: (1) the determination of the total number of possible ways to construct a given ring by 2-, 3-, and 4-component couplings; and (2) the systematic enumeration of those possibilities. The results of the method are illustrated using cyclohexanone, pyrazole, and the Biginelli adduct as target ring systems with a view to discover new and greener strategies for their construction using multicomponent reactions. The application of the method is also extended to various heterocycles found in many natural products and pharmaceuticals.

Tertiary amines react rapidly and reversibly with arylketenes in acetonitrile forming observable zwitterions, and these undergo amine catalyzed dealkylation forming N,N-disubstituted amides. Reactions of N-methyldialkylamines show a strong preference for methyl group loss by displacement, as predicted by computational studies. Loss of ethyl groups in reactions with triethylamine also occur by displacement, but preferential loss of isopropyl groups in the phenylketene reaction with diisopropylethylamine evidently involves elimination. Quinuclidine rapidly forms long-lived zwitterions with arylketenes, providing a model for catalysis by cinchona and related alkaloids in stereoselective additions to ketenes.

Four generations of chemoenzymatic approaches to oseltamivir are presented. The first two generations relied on the use of cyclohexadiene-cis-diol derived enzymatically from bromobenzene. The third and fourth generation used the corresponding diol obtained from ethyl benzoate by fermentation with E. coli JM109(pDTG601a). Oseltamivir was obtained from ethyl benzoate by intersecting intermediate 39 (third-generation synthesis) and intermediate 45 (fourth-generation synthesis). Both of these advanced approaches benefited from symmetry considerations and translocation of the acrylate double bond with concomitant elimination of the C-1 hydroxyl. The syntheses are evaluated for overall efficiency by the use of efficiency metrics and compared with other syntheses of oseltamivir (both academic and industrial).

Flash vacuum thermolysis (FVT) of 1-(dimethylamino)pyrrole-2,3-diones 5 causes extrusion of CO with formation of transient hydrazonoketenes 7. The transient ketenes 7 are observable in the form of weak bands at 2130 (7a) or 2115 cm-1 (7b) in the Ar matrix IR spectra resulting from either FVT or photolysis of either 5 or 1,1-dimethylpyrazolium-5-oxides 8, and these absorptions are in excellent agreement with B3LYP/6-31G* frequency calculations. Under FVT conditions the ketenes 7 cyclize to pyrazolium oxides 8, which undergo 1,4-migration of a methyl group to yield 1,4-dimethyl-3-phenylpyrazole-5(4H)-one 9a and 1,4,4-trimethyl-3- phenylpyrazole-5(4H)-one 9b. All three tautomers of 9a have been characterized, viz. the CH form 9a (most stable form in the gas phase, the solid state and solvents of low polarity), the OH form 9a' (metastable solid at room temperature) and the NH form 9a" (stable in aprotic dipolar solvents). The isomeric 1,4-dimethyl-5-phenylpyrazole-3(2H)- one 12 tautomerizes to the 3-hydroxypyrazole 12'. The crystal structure of the hydrochloride 14 of 9a'/9a" is reported, representing the first structurally characterised example of a protonated 5-hydroxypyrazole.