Continuous-flow reactors for the rapid evolution and validation of kinetic motifs

In this paper we apply the concept of a kinetic motif as a simple way to represent all the time-dependent behaviour in a single-step or multi-step reaction system. Small-scale continuous-flow reactors offer the potential to rapidly collect large amounts of data while accessing conventionally challenging experimental conditions. The scope of the approach is demonstrated on reaction case study examples

Rapid production of block copolymer nano-objects via continuous-flow ultrafast RAFT dispersion polymerisation

Ultrafast RAFT polymerisation is exploited under dispersion polymerisation conditions for the synthesis of poly(dimethylacrylamide)-b-poly(diacetoneacrylamide) (PDMAmx-b-PDAAmy) diblock copolymer nanoparticles. This process is conducted within continuous-flow reactors, which are well suited to fast reactions and can easily dissipate exotherms making the process potentially scalable. Transient kinetic profiles obtained in-line via low-field flow nuclear magnetic resonance spectroscopy (flow-NMR) confirmed the rapid rate of polymerisation whilst still maintaining pseudo first order kinetics. Gel permeation chromatography (GPC) reported molar mass dispersities, Đ < 1.3 for a series of PDMAmx-b-PDAAmy diblock copolymers (x = 46, or 113; y = 50, 75, 100, 150 and 200) confirming control over molecular weight was maintained. Particle characterisation by dynamic light scattering (DLS) and transmission electron microscopy (TEM) indicated successful preparation of spheres and a majority worm phase at 90 °C but the formation of vesicular morphologies was only possible at 70 °C. To maintain the rapid rate of reaction at this lower temperature, initiator concentration was increased which was also required to overcome the gradual ingress of oxygen into the PFA tubing which was quenching the reaction at low radical concentrations. Illdefined morphologies observed at PDAAm DPs close to the worm-vesicle boundary, combined with a peak in molar mass dispersity suggested poor mixing prevented an efficient morphological transition for these samples. However, by targeting higher PDAAm DPs, the additional monomer present during the transition plasticises the chains to facilitate formation of vesicles at PDAAm DPs of ≥300

The Economic Impact of Blindness in Europe

Purpose: To estimate the annual loss of productivity from blindness and moderate to severe visual impairment (MSVI) in the population aged >50 years in the European Union (EU). Methods: We estimated the cost of lost productivity using three simple models reported in the literature based on (1) minimum wage (MW), (2) gross national income (GNI), and (3) purchasing power parity-adjusted gross domestic product (GDP-PPP) losses. In the first two models, assumptions included that all individuals worked until 65 years of age, and that half of all visual impairment cases in the >50-year age group would be in those aged between 50 and 65 years. Loss of productivity was estimated to be 100% for blind individuals and 30% for those with MSVI. None of these models included direct medical costs related to visual impairment. Results: The estimated number of blind people in the EU population aged >50 years is ~1.28 million, with a further 9.99 million living with MSVI. Based on the three models, the estimated cost of blindness is €7.81 billion, €6.29 billion and €17.29 billion and that of MSVI €18.02 billion, €24.80 billion and €39.23 billion, with their combined costs €25.83 billion, €31.09 billion and €56.52 billion, respectively. The estimates from the MW and adjusted GDP-PPP models were generally comparable, whereas the GNI model estimates were higher, probably reflecting the lack of adjustment for unemployment. Conclusion: The cost of blindness and MSVI in the EU is substantial. Wider use of available cost-effective treatment and prevention strategies may reduce the burden significantly

Salt enhanced solvent relaxation and particle surface area determination via rapid spin-lattice NMR

This paper demonstrates the influence of surface charge chemistry on the application of nuclear magnetic relaxation measurements (NMR relaxometry) for the in situ determination of particle surface area, in the presence of high electrolyte concentration. Specifically, dispersions of titania, calcite and silica with and without 1 M KCl were investigated. The addition of salt, showed no significant change to relaxation measurements for titanium dioxide; however, a significant rate enhancement was observed for both calcite and silica systems. These differences were attributed to counterion layers forming as a result of the particles surface charge, leading to an increase in the relaxation rate of bound surface layer water. Further, changes appeared to be more pronounced in the silica systems, due to their larger charge. No enhancement was observed for titania, which was assumed to be due to the particles being at their isoelectric point, with no resulting counterion layer formation. Solvent relaxation was further used to successfully determine the surface area of particles in a dispersion using a silica standard reference material, with results compared to Brunauer-Emmett-Teller (BET) and spherical equivalent estimations. Two different dispersions of titanium dioxide, of different crystal phases, were shown to have NMR surface area measurements in good agreement with BET. Thus showing the technique was able to measure changes in surface charge when surface chemistry remained relatively similar, due to the reference silica material also being an oxide. In contrast, the NMR technique appeared to overestimate the calcite surface areas in reference to BET, which was assumed to occur due to both better dispersion in the liquid state of nanocrystallites and potential ion enhancement from the solubility of the calcite. These results highlight the potential of this technique as a fast, non-destructive and non-invasive method for dispersion analysis, but also show the competition between surface area and surface chemistry interactions on measured relaxation rates

Making electrochemistry easily accessible to the synthetic chemist

A significantly renewed interest in synthetic electrochemistry is apparent in the increasing number of publications over the last few years. Electrochemical synthesis offers a mild, green and atom efficient route to interesting and useful molecules, thus avoiding harsh chemical oxidising and reducing agents used in traditional synthetic methods. As such, encouraging broader application of electrochemistry by synthetic chemists should be a priority. Despite the renewed interest there remains a barrier to widespread adoption of this technology derived from the extra knowledge and specialised equipment required. This has led to a knowledge gap between experienced electrochemists and those new in the field. In this tutorial we will bridge the knowledge gap by providing an easily accessible introduction which will enable synthetic chemists new to the field to explore electrochemistry. We will discuss mechanistic considerations, the setup of an electrochemical reaction with all its components, trouble shooting and selected examples from the literature

Alternating polarity for enhanced electrochemical synthesis

Synthetic electrochemistry has recently become an exciting technology for chemical synthesis. The majority of reported syntheses use either constant current or constant potential, however a few use nonlinear profiles – mostly alternating polarity – to maintain efficiency throughout the process, such as controlling deposits on electrodes or ensuring even use of electrodes. However, even though parameters that are associated with such profiles, such as the frequency, can have a major impact on the reaction outcome, they are often not investigated. Herein, we report the crucial impact that the applied frequency of the alternating polarity has on the observed reaction rate of Cu(I)–NHC complex formation and demonstrate that this can be manipulated to give enhanced yield that is stable over extended reaction times

Algorithms for the self-optimisation of chemical reactions

Self-optimising chemical systems have experienced a growing momentum in recent years, with the evolution of self-optimising platforms leading to their application for reaction screening and chemical synthesis. With the desire for improved process sustainability, self-optimisation provides a cheaper, faster and greener approach to the chemical development process. The use of such platforms aims to enhance the capabilities of the researcher by removing the need for labor-intensive experimentation, allowing them to focus on more challenging tasks. The establishment of these systems have enabled opportunities for self-optimising platforms to become a key element of a laboratory’s repertoire. To enable the wider adoption of self-optimising chemical platforms, this review summarises the history of algorithmic usage in chemical reaction self-optimisation, detailing the functionality of the algorithms and their applications in a way that is accessible for chemists and highlights opportunities for the further exploitation of algorithms in chemical synthesis moving forward

Valsalva retinopathy in pregnancy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Valsalva retinopathy is a unilateral or bilateral condition that occurs when increased intra-thoracic or intra-abdominal pressure transmitted to the eye causes a sharp rise in the intra-ocular venous pressure, and rupture of superficial retinal capillaries. The patient often gives a history of a recent strenuous physical act, which could have increased the intra-thoracic pressure. Pregnancy is known to be a risk factor for Valsalva retinopathy.</p> <p>Case presentation</p> <p>A 23-year-old woman in her seventh month of pregnancy presented with a history of decreased vision in her left eye of one-week duration. Examination of the affected eye showed best corrected visual acuity of 20/50, and fundus examination revealed a pre-retinal hemorrhage located in the macula. Based on clinical findings, the diagnosis of Valsalva retinopathy was made.</p> <p>Conclusion</p> <p>Retinal hemorrhages can be generated by Valsalva maneuvers. Pregnancy is a known risk factor for Valsalva retinopathy; however, the diagnosis should be made only after excluding other causes of retinal hemorrhages. It is a self-limited event. We report a case of Valsalva retinopathy complicating normal pregnancy and confirm that, to date, there is no evidence to indicate that there is a risk of recurrence following spontaneous vaginal delivery.</p

Lessons learned from the development and implementation of a patient-reported outcome and experience measure (POEM) in an Australian glaucoma practice.

BACKGROUND: A patient's perception of how their glaucoma is managed will influence both adherence to their medication and outcome measures such as quality of life. METHODS: Prospective consecutive study using a Glaucoma Patient-reported Outcome and Experience Measure (POEM) modified for an Australian ophthalmic private clinical practice setting. The Australian Glaucoma POEM consists of eight items related to the patient's understanding of the diagnosis and management, acceptability of the treatment, whether they feel their glaucoma is getting worse, interfering with their daily life and concerns regarding loss of vision as well as addressing whether they feel safe under the care of their glaucoma team and how well their care is organised. RESULTS: Two hundred and two patients (M:F 91:111) participated in the study. Mean ± standard deviation for subject age was 69 ± 13 years. Patient's overall perception of their treatment and outcome was favourable. Younger patients felt their glaucoma interfered more with their daily lives and were more worried about losing vision from glaucoma. The greater the number of medications in use, the more they felt their glaucoma was getting worse and that glaucoma interfered with their daily lives. With all other variables accounted for by the multivariate linear model, female patients more strongly agreed that they understood their glaucoma diagnosis and glaucoma management. The patients with a severe visual defect in their worse eye, reported a greater perceived understanding of their glaucoma diagnosis and management and that they felt that glaucoma had a greater interference on their daily life. They were also more concerned about losing vision from glaucoma than their fellow glaucoma patients with less severe or no visual field deficit in the worse eye. CONCLUSIONS: The modified POEM demonstrates potential to capture the concerns of a practice's glaucoma cohort with a view to enhancing the quality of glaucoma care delivered

A Hybridised Optimisation of an Automated Photochemical Continuous Flow Reactor

A new hybridized algorithm that combines process optimisation with response surface mapping was developed and applied in an automated continuous flow reaction. Moreover, a photochemical cascade CSTR was developed and characterised by chemical actinometry, showing photon flux density of ten times greater than previously reported in batch. The success of the algorithm was then evaluated in the aerobic oxidation of sp3 C–H bonds using benzophenone as photosensitizer in the newly developed photo reactor