A multi-phase DES modelling framework for patient-centred care

We provide a framework for simulating the entire patient journey across different phases (such as diagnosis, treatment, rehabilitation and long-term care) and different sectors (such as GP, hospital, social and community services), with the aim of providing better understanding of such processes and facilitating evaluation of alternative clinical and care strategies. A phase-type modelling approach is used to promote better modelling and management of the specific elements of a patient pathway, using performance measures such as clinical outcomes, patient quality of life, and cost. The approach is illustrated using stroke disease. Approximately 5% of the United Kingdom National Health Service budget is spent treating stroke disease each year. There is an urgent need to assess whether existing services are cost-effective or new interventions could increase efficiency. This assessment can be made using models across primary and secondary care; in particular we evaluate the cost-effectiveness of thrombolysis (clot busting therapy), using discrete event simulation. Using our model, patient quality of life and the costs of thrombolysis are compared under different regimes. In addition, our simulation framework is used to illustrate the impact of internal discharge queues, which can develop while patients are awaiting placement. Probabilistic Sensitivity Analysis of the value parameters is also carried out.     

Divalent dirhodium imido complexes: formation, structure, and alkyne cycloaddition reactivity

Dirhodium amido complexes [(Cp*Rh)2(mu2-NHPh)(mu2-X)] (X = NHPh (2), Cl (3), OMe (4); Cp* = eta5-C5Me5) were prepared by chloride displacement of [Cp*Rh(mu2-Cl)]2 (1) and have been used as precursors to a dirhodium imido species [Cp*Rh(mu2-NPh)RhCp*]. The imido species can be trapped by PMe3 to give the adduct [Cp*Rh(mu2-NPh)Rh(PMe3)Cp*] (5) and undergoes a formal [2 + 2] cycloaddition reaction with unactivated alkynes to give the azametallacycles [Cp*Rh(mu2-eta2:eta3-R1CCR2NPh)RhCp*] (R1 = R2 = Ph (6a), R1 = H, R2 = t-Bu (6b), R1 = H, R2 = p-tol (6c)). Isolation of a relevant unsaturated imido complex [Cp*Rh(mu2-NAr)RhCp*] (7) was achieved by the use of a sterically hindered LiNHAr (Ar = 2,6-diisopropylphenyl) reagent in a metathesis reaction with 1. X-ray structures of 2, 6a, 7 and the terminal isocyanide adduct [Cp*Rh(mu2-NAr)Rh(t-BuNC)Cp*] (8) are reported.     

Biomimetic nanostructures: creating a high-affinity zinc-binding site in a folded nonbiological polymer

One of the long-term goals in developing advanced biomaterials is to generate protein-like nanostructures and functions from a completely nonnatural polymer. Toward that end, we introduced a high-affinity zinc-binding function into a peptoid (N-substituted glycine polymer) two-helix bundle. Borrowing from well-understood zinc-binding motifs in proteins, thiol and imidazole moieties were positioned within the peptoid such that both helices must align in close proximity to form a binding site. We used fluorescence resonance energy transfer (FRET) reporter groups to measure the change of the distance between the two helical segments and to probe the binding of zinc. We systematically varied the position and number of zinc-binding residues, as well as the sequence and size of the loop that connects the two helical segments. We found that certain peptoid two-helix bundles bind zinc with nanomolar affinities and high selectivity compared to other divalent metal ions. Our work is a significant step toward generating biomimetic nanostructures with enzyme-like functions.     

Enantioselective Total Syntheses of Preussomerins: Control of Spiroacetal Stereogenicity by Photochemical Reaction of a Naphthoquinone through 1,6-Hydrogen Atom Transfer

We report the enantioselective total syntheses of preussomerins EG₁, EG₂, and EG₃. The key transformation is a stereospecific photochemical reaction involving 1,6-hydrogen atom transfer to achieve retentive replacement of a C−H with a C−O bond, enabling otherwise-difficult control of the spiroacetal stereogenic center.     

Controlling the Photofunctionality of a Polyanionic Heteroleptic Copper(I) Photosensitizer for CO2 Reduction Using Its Ion-pair Formation with Polycationic Ammonium in Aqueous Media

A water-soluble trianionic heteroleptic copper(I) photosensitizer having four sulfonate groups ( CuPS ³⁻) was found to afford the 1 : 2 ion-pair adduct with dicationic alkylammonium (hexamethonium) cations ( HM ²⁺) in aqueous media, leading to exhibit excellent photophysical and photocatalytic performances owing to the substantial suppression of water-derived non-radiative decay of the photoexcited state.     

Carbazole-Dendronized Luminescent Radicals

A series of carbazole-dendronized tris(2,4,6-trichlorophenyl)methyl (TTM) radicals have been synthesized. The photophysical properties of dendronized radicals up to the fourth generation were compared systematically to understand how structure–property relationships evolve with generation. The photoluminescence quantum yield (PLQY) was found to increase with the increasing generation, and the fourth generation (G4TTM) in cyclohexane solution showed a PLQY as high as 63 % at a wavelength of 627 nm (in the deep-red region) from the doublet state. The dendron modification strategy also showed a blue-shift of the emission on increasing the generation number, and the photostability was also increased compared to the bare TTM radical.     

Convergent and rapid assembly of substituted 2-pyridones through formation of N-alkenyl alkynylamides followed by gold-catalyzed cycloisomerization

A new method for the convergent and rapid assembly of substituted 2-pyridones was developed through the formation of N-alkenyl alkynylamides (amide-linked 1,5-enynes) by N-acylation of imines with alkynoyl chlorides and the subsequent cationic Au(I)/PPh 3-catalyzed cycloisomerization.     

Rhodium-catalyzed highly enantio- and diastereoselective cotrimerization of alkenes and dialkyl acetylenedicarboxylates leading to furylcyclopropanes

A cationic rhodium(I)/Segphos or H(8)-BINAP complex catalyzes the unprecedented cotrimerization of commercially available monoenes and dialkyl acetylenedicarboxylates, leading to functionalized furylcyclopropanes with excellent enantioselectivity and perfect diastereoselectivity.