The Reaction of a Nitro-Capped Cobalt(III) Cage Complex With Base: the Crystal Structure of a Contracted Cage Complex, and the Mechanism of Its Formation

The synthesis, properties and crystal structure of the cage complex (1-hydroxy-8-methyl-3,6,10,13,15,18-hexaazabicyclo[6.6.5]nonadecane)cobalt(III) chloride hydrate ([Co(Me,OH-absar)] C13.H2O) are reported. The mechanism of the formation of this contracted cavity cage from a nitro-capped hexaazabicycloicosane type cage has been investigated. Treatment of (1-methyl-8-nitro-3,6,10,13,16,19-hexaazabicyclo[6.6.6]icosane)cobalt(III) chloride ([Co(Me,NO2-sar)] 3+) with excess base in aqueous solution leads initially to rapid (t1/2 < 1 ms) and reversible deprotonation of one coordinated secondary amine. This species undergoes a retro-Mannich type reaction and imine hydrolysis (t1/2 almost-equal-to 90 s). Quenching the reaction with acid gives rise to a pair of isomeric intermediate species which have been isolated and characterized. They have a pendant arm macrocyclic structure, resulting from the loss of a methylene unit from one of the arms of the cap. Heating either isomer in aqueous solution gives the new cage compound with the contracted cap. It is postulated that this occurs through a Nef reaction, resulting in the formation of a ketone which then condenses with the coordinated primary amine. A comparison with the corresponding bicycloicosane analogue indicates a reduced chromophoric cavity size for the contracted cage. The reduction potential of the cobalt(III)/cobalt(II) couple is 170 mV more negative for the smaller cage, and, in the electronic spectrum of the cobalt(III) complex, the d-d transitions are both shifted to higher energy, corresponding to a stronger ligand field

Evaluating the effect of inequalities in oral anti-coagulant prescribing on outcomes in people with atrial fibrillation

Background Whilst anti-coagulation is typically recommended for thromboprophylaxis in atrial fibrillation (AF), it is often never prescribed, or prematurely discontinued. The aim of this study was to evaluate the effect of inequalities in anti-coagulant prescribing by assessing stroke/systemic embolism (SSE) and bleeding risk in people with AF who continue anticoagulation compared with those who stop transiently, permanently, or never start. Methods This retrospective cohort study utilised linked Scottish healthcare data to identify adults diagnosed with AF between January 2010 and April 2016, with a CHA2DS2-VASC score of ≥2. They were sub-categorised based on anti-coagulant exposure: never started, continuous, discontinuous, and cessation. Inverse probability of treatment weighting-adjusted Cox regression and competing-risks regression were utilised to compare SSE and bleeding risks between cohorts during five year follow-up. Results Of an overall cohort of 47,427 people, 26,277 (55.41%) were never anti-coagulated, 7,934 (16.72%) received continuous anti-coagulation, 9,107 (19.2%) temporarily discontinued and 4,109 (8.66%) permanently discontinued. Lower socio-economic status, elevated frailty score, and age ≥75 were associated with a reduced likelihood of initiation and continuation of anti-coagulation. SSE risk was significantly greater in those with discontinuous anti-coagulation, compared to continuous (SHR: 2.65; 2.39-2.94). In the context of a major bleeding event, there was no significant difference in bleeding risk between the cessation and continuous cohorts (SHR 0.94; 0.42-2.14). Conclusion Our data suggest significant inequalities in anti-coagulation prescribing, with substantial opportunity to improve initiation and continuation. Decision-making should be patient-centered and must recognise that discontinuation or cessation is associated with considerable thromboembolic risk not offset by mitigated bleeding risk