Cryphonectria parasitica Detections in England, Jersey, and Guernsey during 2020-2023 Reveal Newly Affected Areas and Infections by the CHV1 Mycovirus.

In England, Cryphonectria parasitica was detected for the first time in 2011 in a nursery and in 2016 in the wider environment. Surveys between 2017 and 2020 identified the disease at different sites in Berkshire, Buckinghamshire, Cornwall, Derbyshire, Devon, Dorset, London, West Sussex, and the island of Jersey, while the present study comprises the results of the 2020-2023 survey with findings in Derbyshire, Devon, Kent, Nottinghamshire, Herefordshire, Leicestershire, London, West Sussex, and the islands of Jersey and Guernsey. A total of 226 suspected samples were collected from 72 surveyed sites, as far north as Edinburgh and as far west as Plymouth (both of which were negative), and 112 samples tested positive by real-time PCR and isolation from 35 sites. The 112 isolates were tested for the vegetative compatibility group (VCG), mating type, and Cryphonectria hypovirus 1 (CHV1). Twelve VCGs were identified, with two of them (EU-5 and EU-22) being the first records in the UK. Both mating types were present (37% MAT-1 and 63% MAT-2), but only one mating type was present per site and VCG, and perithecia were never observed. Cryphonectria hypovirus 1 (CHV1), consistently subtype-I haplotype E-5, was detected in three isolates at a low concentration (5.9, 21.1, and 33.0 ng/µL) from locations in London, Nottinghamshire, and Devon.

Efficacy and Safety of Native and Recombinant Zona Pellucida Immunocontraceptive Vaccines Formulated with Non-Freund's Adjuvants in Donkeys.

This study aimed to test zona pellucida (ZP) vaccines' immunocontraceptive efficacy and safety when formulated with non-Freund's adjuvant (6% Pet Gel A and 500 Μg Poly(I:C)). Twenty-four jennies were randomly assigned to three treatment groups: reZP (n = 7) received three doses of recombinant ZP vaccine; pZP (n = 9) received two doses of native porcine ZP; and Control group (n = 8) received two injections of placebo. Jennies were monitored weekly via transrectal ultrasonography and blood sampling for serum progesterone profiles and anti-pZP antibody titres. In addition, adverse effects were inspected after vaccination. Thirty-five days after the last treatment, jacks were introduced to each group and rotated every 28 days. Vaccination with both pZP and reZP was associated with ovarian shutdown in 44% (4/9) and 71% (4/7) of jennies, 118 ± 33 and 91 ± 20 days after vaccination, respectively (p > 0.05). Vaccination delayed the chances of a jenny becoming pregnant (p = 0.0005; Control, 78 ± 31 days; pZP, 218 ± 69 days; reZP, 244 ± 104 days). Anti-pZP antibody titres were elevated in all vaccinated jennies compared to Control jennies (p < 0.05). In addition, only mild local injection site reactions were observed in the jennies after treatment. In conclusion, ZP vaccines formulated with non-Freund's adjuvant effectively controlled reproduction in jennies with only minor localised side effects.

Key stakeholder experiences of an integrated healthcare pilot in Australia: a thematic analysis.

BACKGROUND: In Australia and other developed countries, chronic illness prevalence is increasing, as are costs of healthcare, particularly hospital-based care. Integrating healthcare and supporting illness management in the community can be a means of preventing illness, improving outcomes and reducing unnecessary hospitalisation. Western Sydney has high rates of diabetes, heart and respiratory diseases and the NSW State Ministry of Health funded a range of key strategies through the Western Sydney Integrated Care Program (WSICP) to integrate care across hospital and community settings for patients with these illnesses. Complementing our previously reported analysis related to specific WSICP strategies, this research provided information concerning overall experiences and perspectives of WSICP implementation and integrated care generally. METHODS: We administered 125 in-depth interviews in two rounds over 12 months with 83 participants including patients and their carers, care facilitators, hospital specialists and nurses, allied health professionals, general practitioners and primary care nurses, and program managers. Half of the participants (n = 42) were interviewed twice. We conducted an inductive, thematic analysis on the interview transcripts. RESULTS: Key themes related to the set-up and operationalising of WSICP; challenges encountered; and the added value of the program. Implementing WSICP was a large and time consuming undertaking but challenges including those with staffing and information technology were being addressed. The WSICP was considered valuable in reducing hospital admissions due to improved patient self-management and a focus on prevention, greater communication and collaboration between healthcare providers across health sectors and an increased capacity to manage chronic illness in the primary care setting. CONCLUSIONS: Patients, carers and health providers experienced the WSICP as an innovative integrated care model and valued its patient-centred approach which was perceived to improve access to care, increase patient self-management and illness prevention, and reduce hospital admissions. Long-term sustainability of the WSICP will depend on retaining key staff, more effectively sharing information including across health sectors to support enhanced collaboration, and expanding the suite of activities into other illness areas and locations. Enhanced support for general practices to manage chronic illness in the community, in collaboration with hospital specialists is critical. Timely evaluation informs ongoing program implementation.

Efficacy and safety of native and recombinant zona pellucida immunocontraceptive vaccines in donkeys.

Feral and semi-feral donkeys are recognised as a problem in some world regions. The main problem associated with uncontrolled donkey populations is habitat degradation and competition for feed resources, especially in arid climes. Controlling population numbers would reduce the impact of donkeys and other species. While removal by various means is effective, it has been shown to stimulate reproductive rate. Probably the most effective and humane solution is reducing reproduction using minimally invasive methods including immunocontraception. This study tested the immunocontraceptive efficacy and safety of zona pellucida (ZP) vaccines, both recombinant (reZP; three treatments) and native porcine (pZP; two treatments) vaccines formulated with Freund's modified complete (primary) and Freund's incomplete (boosters) adjuvants in donkey jennies. Control jennies received adjuvants only (two treatments). Twenty-five non-pregnant jennies were randomly assigned to reZP (n = 9), pZP (n = 8) or control (n = 8) groups. Weekly monitoring of the reproductive tract and ovaries via transrectal palpation and ultrasound and inspection of injection sites was conducted and anti-pZP antibody titers were measured. Five weeks after last treatment, one donkey jack was introduced to each group and rotated every 21 days. By 232 days after last treatment the number pregnant and median days to pregnancy was 2/9 and 214 (reZP group), 1/8 and 196 (pZP group) and 8/8 and 77 (control group). Median time to ovarian shut-down was 77 (9/9) and 56 (7/8) days for reZP and pZP groups, respectively. This was observed in association with a distinct reduction in mean uterine diameter. The antibody response was equally good for both ZP-treated groups. Incorporation of Freund's adjuvants initially produced a high incidence of side effects from local swelling and intermittent lameness followed weeks later by sterile abscesses (reZP, 9/9; pZP, 7/8; control, 3/8). Both ZP vaccines effectively controlled reproduction in jennies, albeit with a high incidence of adjuvant-associated side effects.

Production of foot-and-mouth disease virus SAT2 VP1 protein.

The seven serotypes of foot-and-mouth disease virus (FMDV) differ on the surface exposed regions on the VP1, 2 and 3 proteins. Amongst the three, the VP1 protein has been produced the most for use in serotyping assays for some of the Euro-Asian serotypes. In this study the VP1 protein of the FMDV SAT2/ZIM/7/83 was expressed in Escherichia coli BL21 cells in Luria broth and EnPresso® B media in shake flasks. Production was further developed and the VP1 protein was produced at 2.15 g L-1 in fed-batch fermentations at 2 L scale. The protein formed insoluble inclusion bodies that were isolated, denatured and refolded. When tested in ELISA, the protein was found to be highly reactive with serum from a SAT2 vaccinated guinea pig, and not reactive to SAT1 and SAT3 antisera. These results open avenues to evaluate recombinantly expressed VP1 proteins for differentiation of the three Southern African Territories serotypes of FMDV that co-occur in Southern and East Africa. In addition, this could mitigate the need for employing virus as reagent, or having to raise reagent antibodies.

Integrating health care in Australia: a qualitative evaluation.

BACKGROUND: With aging populations, a growing prevalence of chronic illnesses, higher expectations for quality care and rising costs within limited health budgets, integration of healthcare is seen as a solution to these challenges. Integrated healthcare aims to overcome barriers between primary and secondary care and other disconnected patient services to improve access, continuity and quality of care. Many people in Australia are admitted to hospital for chronic illnesses that could be prevented or managed in the community. Western Sydney has high rates of diabetes, heart and respiratory diseases and the NSW State Ministry of Health has implemented key strategies through the Western Sydney Integrated Care Program (WSICP) to enhance primary care and the outcomes and experiences of patients with these illnesses. METHODS: We aimed to investigate the WSICP's effectiveness through a qualitative evaluation focused on the 10 WSICP strategies using a framework analysis. We administered 125 in-depth interviews in two rounds over 12 months with 83 participants including patients and their carers, care facilitators, hospital specialists and nurses, allied health professionals, general practitioners (GPs) and primary care nurses, and program managers. Most participants (71%) were interviewed twice. We analysed data within a framework describing how strategies were implemented and used, the experiences around these, their perceived value, facilitators and barriers, and participant-identified suggestions for improvement. RESULTS: Care facilitators helped patients access services within the hospital and in primary care and connected general practices with hospital specialists and services. Rapid access and stabilisation clinics with their patient hotlines assisted patients and carers to self-manage chronic illness while connecting GPs to specialists through the GP support-line. Action plans from the hospital informed GPs and their shared care plans which could be accessed by other community health professionals and patients. HealthPathways provided GPs with local, evidence-based guidelines for managing patients. Difficulties persisted in effective widespread access to shared records and electronic communication across sectors. CONCLUSIONS: The combined WSICP strategies improved patient and carer experience of healthcare and capacity of GPs to provide care in the community. Information sharing required longer-term investment and support, though benefits were evident by the end of our research.

Model for integrated care for chronic disease in the Australian context: Western Sydney Integrated Care Program.

Objective To describe the implementation of a model of integrated care for chronic disease in Western Sydney. This model was established on the basis of a partnership between the Local Health District and the Primary Health Network. Methods The Western Sydney Integrated Care Program (WSICP) focuses on people with type 2 diabetes, chronic obstructive pulmonary disease and coronary artery disease or congestive cardiac failure. We describe the design of the program, the processes involved and some of the challenges and barriers to integration. Results Early data indicate a high uptake of services, with some evidence of a reduction in hospital admissions and presentations to the emergency department. Conclusion A model of integrated care has been successfully implemented and embedded into local practices. Preliminary data suggest that this is having an impact on the utilisation of hospital services. What is known about the topic? There is evidence that integrated models can improve cost-effectiveness and the quality of clinical care for people with chronic disease. However, most integrated models are small scale, focus on very specific populations and generally do not engage both primary care and acute hospitals. What does this paper add? This paper describes an effective partnership between state-funded hospital services in the WSLHD and the federally funded local Primary Health Network (PHN) of general practitioners. The paper outlines the design of the program and the structural, governance and clinical steps taken to embed integrated care into everyday clinical practice. In addition, preliminary results indicate a reduction in the use of hospital services by people who have received integrated care services. What are the implications for practitioners? Involvement of both primary care and the public hospital system is important for a successful and sustainable integrated care program. This is a long and challenging process, but it can lead to positive effects not just for individuals, but also for the health system as a whole.

Serum antibody immunoreactivity and safety of native porcine and recombinant zona pellucida vaccines formulated with a non-Freund's adjuvant in horses.

Commercial and regulatory limitations associated with native porcine zona pellucida (pZP) vaccines formulated with Freund's adjuvants may be overcome by developing effective recombinant ZP vaccines (reZP) and identifying alternative adjuvant formulations. A two-part preparatory study used 15 geldings and identified potentially effective alternative adjuvant formulations based on anti-pZP antibody response following treatment with pZP formulated with Addavax (AddaVax ™, Invivogen), Quil A (Quil-A® Adjuvant, Invivogen), Quil A and Poly (I:C) (HMW VacciGrade™, Invivogen), Pet Gel A (Montanide™ Pet Gel A, Seppic) and Pet Gel A and Poly (I:C). Injection site reactions, rectal temperature and respiratory and heart rates were also monitored for three days post-treatment. Suitable anti-pZP antibody titres were seen in response to Pet Gel A and Pet Gel A and Poly (I:C). Subsequently in 31 mares, following administration of pZP, reZP and a combination of pZP and reZP proteins prepared in Pet Gel A and Poly (I:C), both serum anti-pZP and -reZP antibody responses were monitored. In addition, safety was assessed for up to seven days post-treatment by inspection and palpation of gluteal intramuscular injection sites and measurement of rectal temperature. The measured antibody titres in all treatment groups differed significantly to an adjuvant control group (P < 0.001). Temporal changes in both anti-pZP and -reZP antibody titres in all ZP treatment groups were similar to patterns reported previously in various species vaccinated with pZP formulated with Freund's adjuvants. There were no differences in anti-pZP antibody titres between the pZP and reZP treated groups (P > 0.05). Side effects were mild and transient in nature. This represents the first application of a reZP vaccine formulated with non-Freund's adjuvants evoking a similar antibody titre response to native pZP vaccination in mares.

Ovarian function following immunocontraceptive vaccination of mares using native porcine and recombinant zona pellucida vaccines formulated with a non-Freund's adjuvant and anti-GnRH vaccines.

An important determinant in the selection of any contraceptive agent is the impact on ovarian function, both in the short and longer term. In this study, ovarian activity was monitored in mares immunised with one of the following vaccine formulations; native porcine zona pellucida (pZP), recombinant zona pellucida proteins ZP3 and ZP4 (reZP), pZP and reZP combined or a commercially available anti-GnRH vaccine. The ZP antigens were prepared in an adjuvant formulation consisting of 6% polymeric adjuvant (Montanide™ PetGel A, Seppic, France) and 500 µg polyinosinic-polycytidylic acid - TLR3-agonist (Poly(I:C) HMW VacciGrade™, Invivogen, USA). A vehicle-only control group was administered the adjuvant formulation without antigen. Ovarian activity was monitored using clinical observations (transrectal palpation and ultrasonography of the reproductive tract) in addition to blood sampling for serum progesterone and anti-Müllerian hormone (AMH) concentrations while employing a low sampling frequency. Treatments and measurements were initiated in December (southern hemisphere summer) and subsequent data collection was performed in January, February, March and May. Both reZP and anti-GnRH vaccination were associated with clinically evident ovarian suppression in the short term. Ovarian activity in mares administered a reZP or anti-GnRH vaccine was significantly different to adjuvant control and pZP treated mares. Serum AMH concentrations were different between pZP and anti-GnRH treated mares 3.5 months after the final vaccination. Serum AMH concentrations were significantly correlated with mare age, serum progesterone and ovarian volume.

Evaluation of plant-produced Clostridium perfringens type D epsilon toxoid in a vaccine against enterotoxaemia in sheep.

Enterotoxaemia (pulpy kidney) is a common bacterial disease of sheep caused by Clostridium perfringens type D epsilon toxin. It has mortality rates of up to 30% in non-vaccinated animals. Current vaccines from whole cell cultures are expensive to manufacture and can induce local inflammatory responses in sheep. They usually have reduced immunogenicity because of the difficulty of standardising the inactivation step in vaccine manufacturing. In the current study, we evaluated the safety and potency of a recombinant plant-made epsilon toxoid protein (r-Etox) as an affordable and safer alternative vaccine for developing countries. Results of injection site reactions, rectal temperature and toxin neutralisation test in single and prime- boost inoculations of mice, guinea pigs and sheep suggest that the product is not toxic to animals and could protect sheep against enterotoxaemia.

Cattle tick vaccine researchers join forces in CATVAC.

A meeting sponsored by the Bill & Melinda Gates Foundation was held at the Avanti Hotel, Mohammedia, Morocco, July 14-15, 2015. The meeting resulted in the formation of the Cattle Tick Vaccine Consortium (CATVAC).

Analyzing the molecular mechanism of lipoprotein localization in Brucella.

Bacterial lipoproteins possess diverse structure and functionality, ranging from bacterial physiology to pathogenic processes. As such many lipoproteins, originating from Brucella are exploited as potential vaccines to countermeasure brucellosis infection in the host. These membrane proteins are translocated from the cytoplasm to the cell membrane where they are anchored peripherally by a multifaceted targeting mechanism. Although much research has focused on the identification and classification of Brucella lipoproteins and their potential use as vaccine candidates for the treatment of Brucellosis, the underlying route for the translocation of these lipoproteins to the outer surface of the Brucella (and other pathogens) outer membrane (OM) remains mostly unknown. This is partly due to the complexity of the organism and evasive tactics used to escape the host immune system, the variation in biological structure and activity of lipoproteins, combined with the complex nature of the translocation machinery. The biosynthetic pathway of Brucella lipoproteins involves a distinct secretion system aiding translocation from the cytoplasm, where they are modified by lipidation, sorted by the lipoprotein localization machinery pathway and thereafter equipped for export to the OM. Surface localized lipoproteins in Brucella may employ a lipoprotein flippase or the ß-barrel assembly complex for translocation. This review provides an overview of the characterized Brucella OM proteins that form part of the OM, including a handful of other characterized bacterial lipoproteins and their mechanisms of translocation. Lipoprotein localization pathways in gram negative bacteria will be used as a model to identify gaps in Brucella lipoprotein localization and infer a potential pathway. Of particular interest are the dual topology lipoproteins identified in Escherichia coli and Haemophilus influenza. The localization and topology of these lipoproteins from other gram negative bacteria are well characterized and may be useful to infer a solution to better understand the translocation process in Brucella.

The safety of seasonal influenza vaccines in Australian children in 2013.

OBJECTIVE: To examine influenza vaccine safety in Australian children aged under 10 years in 2013. DESIGN, PARTICIPANTS AND SETTING: Active prospective surveillance study conducted with parents or carers of children who received influenza vaccine in outpatient clinics at six tertiary paediatric hospitals or from selected primary health care providers between 18 March and 19 July 2013. MAIN OUTCOME MEASURES: Parental-reported frequency of systemic reactions (fever, headache, nausea, abdominal symptoms, convulsions, rash, rigors and fatigue), injection site reactions (erythema, swelling and/or pain at the injection site), use of antipyretics or analgesics, and medical attendance or advice within 72 hours after vaccination. RESULTS: Of 981 children enrolled in the surveillance, 893 children aged 6 months to < 10 years were eligible for inclusion. These children received 1052 influenza vaccine doses. Fever was reported in 5.5% (95% CI, 4.1%-7.3%) and 6.5% (95% CI, 3.5%-10.9%) of children after Doses 1 and 2, respectively. One febrile convulsion occurred in a child with a known seizure disorder. Injection site reactions occurred in 21.2% (95% CI, 18.5%-24.1%) and 6.0% (95% CI, 3.1%-10.2%) after Doses 1 and 2, respectively; most were mild. Very few parents sought medical follow-up for their child's reaction: 22 (2.6%; 95% CI, 1.6%-3.9%) after Dose 1, and 11 (5.5%; 95% CI, 2.8%-9.6%) after Dose 2. CONCLUSIONS: These results are consistent with clinical trials and other observational studies of influenza vaccines currently registered for use in young children in Australia and can reassure parents and health care providers that influenza vaccination is safe and well tolerated.

Extracellular secretion of a recombinant therapeutic peptide by Bacillus halodurans utilizing a modified flagellin type III secretion system.

BACKGROUND: Through modification of the flagellin type III secretion pathway of Bacillus halodurans heterologous peptides could be secreted into the medium as flagellin fusion monomers. The stability of the secreted monomers was significantly enhanced through gene-targeted inactivation of host cell extracellular proteases. In evaluating the biotechnological potential of this extracellular secretion system an anti-viral therapeutic peptide, Enfuvirtide, was chosen. Currently, Enfuvirtide is synthesised utilizing 106 chemical steps. We used Enfuvirtide as a model system in an effort to develop a more cost-effective biological process for therapeutic peptide production. RESULTS: An attempt was made to increase the levels of the fusion peptide by two strategies, namely strain improvement through gene-targeted knock-outs, as well as vector and cassette optimization. Both approaches proved to be successful. Through chromosomal inactivation of the spo0A, lytC and lytE genes, giving rise to strain B. halodurans BhFDL05S, the secretion of recombinant peptide fusions was increased 10-fold. Cassette optimization, incorporating an expression vector pNW33N and the N- and C-terminal regions of the flagellin monomer as an in-frame peptide fusion, resulted in a further 3.5-fold increase in the secretion of recombinant peptide fusions. CONCLUSIONS: The type III flagellar secretion system of B. halodurans has been shown to successfully secrete a therapeutic peptide as a heterologous flagellin fusion. Improvements to both the strain and expression cassette led to increased levels of recombinant peptide, showing promise for a biotechnological application.

Impact of inactivated extracellular proteases on the modified flagellin type III secretion pathway of Bacillus halodurans.

The flagellin type III secretion pathway of Bacillus halodurans BhFC01 (Deltahag) was modified by the inactivation of fliD. An in-frame flagellin gene fusion polypeptide construct was expressed, and the heterologous peptides were secreted as flagellin fusion monomers. The stability of the secreted monomers was significantly enhanced through gene-targeted inactivation of extracellular proteases.

Kinetic and equilibrium studies of anilinoalkanesulfonate formation.

(1)H NMR studies of the reactions of some hydroxyalkanesulfonates, 1, with aniline derivatives, 2, show the formation at equilibrium of anilinoalkanesulfonates, 3. Kinetic studies in water are consistent with a mechanism involving dissociation of 1 to give the parent aldehyde, which reacts with 2 to give a carbinolamine. Acid-catalysed dehydration of the carbinolamine yields an iminium ion which reacts rapidly with sulfite to give the product 3. Study of the variation with pH of the rate constants of the reaction indicates a change in the nature of the rate-determining step from carbinolamine formation to carbinolamine dehydration as the pH is increased. Variations in values of rate and equilibrium constants with the nature of 1 and 2 are discussed in terms of electronic and steric effects.

Carbanion reactivity, kinetic and equilibrium studies of sigma-adduct formation and elimination in the reactions of 4-nitrobenzofurazan derivatives with nitroalkane anions.

1H NMR studies are reported of the reactions in [2H(6)]-DMSO of 4-nitrobenzofurazan, 2a, and its 7-chloro- and 7-methoxy-derivatives, 2b and 2c respectively, with anions derived from nitromethane, 3, nitroethane, 4, and 2-nitropropane, 5. The initial reactions result in sigma-adduct formation by carbanion attack at the 5-position of 2a-c and in the case of reaction of 2a with 5 the adduct at the 7-position is also observed. These reactions may be followed by base catalysed elimination of nitrous acid to yield anionic alkene derivatives. Kinetic and equilibrium measurements of these reactions were made spectrophotometrically in methanol. The carbon nucleophilicities of the carbanions decrease in the order 3> 4> 5, as also found in their reactions with benzhydrylium cations, and are much lower than the nucleophilicities of some cyano-substituted carbanions. Comparison with corresponding sigma-adduct forming reactions of 1,3,5-trinitrobenzene, TNB, show that here 2 and TNB have similar electrophilicity, although the value of the intrinsic rate coefficient k(o) = 0.05, for reaction of 2 is rather lower than that, k(o) = 0.20, for the TNB reactions. Literature data suggest that for reaction with a variety of nucleophiles 2 and TNB show similar electrophilicities. Measurements of the rates of elimination of nitrous acid from some 5-adducts in methanol catalysed by methoxide ions are reported. Values of rate constants may be influenced both by steric requirements at the reaction centre and by the electronic effects of the 7-substituent.

The development of a flagellin surface display expression system in a moderate thermophile, Bacillus halodurans Alk36.

This study relates to the development of an alkaliphilic, thermotolerant, Gram-positive isolate, Bacillus halodurans Alk36, for the over-production and surface display of chimeric gene products. This bacterium continuously over-produces flagellin. To harness this ability, key genetic tools, such as gene targeted inactivation, were developed for this strain. The hag gene, which codes for flagellin, was inactivated on the chromosome giving rise to the B. halodurans BhFC01 mutant. Polylinkers were inserted as in-frame, chimeric, flagellin sandwich fusions to identify the permissive insertion sites corresponding to the variable regions of the flagellin protein. Flagellin expression and motility were evaluated for these constructs. Two sites were identified for possible peptide insertion in the flagellin gene, one of which produced functional flagella and was able to restore the motility phenotype to a non-motile mutant. Peptides encoding a poly-histidine peptide and the HIV-1 subtype C gp120 epitope were, respectively, incorporated into this site as in-frame fusions. The peptides were found to be successfully displayed on the cell surface and functional through metal binding and immunological studies, respectively.

Rate-limiting proton-transfer in the sigma-adduct forming reactions of 1,3,5-trinitrobenzene and 4-nitrobenzofuroxan with substituted anilines in dimethyl sulfoxide.

Kinetic and equilibrium results are compared for the reactions in dimethyl sulfoxide of 1,3,5-trinitrobenzene, 1, and 4-nitrobenzofuroxan, 4, with a series of substituted anilines in the presence of Dabco or in, some cases, quinuclidine. pKa values for the corresponding anilinium ions are reported. The reactions of 1and 4 are likely to proceed through nucleophilic attack by the aniline to yield zwitterionic intermediates which may transfer an acidic proton to the bases present to yield the anionic adducts 9 or 12 respectively. In the formation of 9 from 1 the proton transfer step is rate-limiting; however, the slower interconversion of 4 and its zwitterion leads to only partial rate-limiting proton transfer in the formation of 12. Results with substituted anilines including 2-substituted and N-methyl aniline indicate that steric effects are not a major factor in determining rates of proton-transfer in these systems. Contrary to previous reports no evidence was found for a strong interaction between 1 and Dabco in DMSO.

The Strecker reaction: kinetic and equilibrium studies of cyanide addition to iminium ions.

Kinetics studies are reported of the reactions of benzylidene benzylamine 4a, and of benzylidene allylamine 4b, with cyanide in aqueous buffers to give the corresponding [small alpha]-aminonitriles. The results allow the calculation of values of rate and equilibrium constants for reaction of the iminium ions formed from 4a and 4b with cyanide ions. These values are compared with those, obtained from the hydrolysis reactions, for reaction of the iminium ions with hydroxide ions and with water. Comparison with some other iminium ions reveals that those formed from 4a and 4b are relatively unreactive due to the possibilities of charge delocalisation.