Exploring coordination-driven self-assembly with autonomous chemical robots

The work presented herein focused on the automation of coordination-driven self assembly, exploring methods that allow syntheses to be followed more closely while forming new ligands, as part of the fundamental study of the digitization of chemical synthesis and discovery. Whilst the control and understanding of the principle of pre-organization and self-sorting under non-equilibrium conditions remains a key goal, a clear gap has been identified in the absence of approaches that can permit fast screening and real-time observation of the reaction process under different conditions. A firm emphasis was thus placed on the realization of an autonomous chemical robot, which can not only monitor and manipulate coordination chemistry in real-time, but can also allow the exploration of a large chemical parameter space defined by the ligand building blocks and the metal to coordinate. The self-assembly of imine ligands with copper and nickel cations has been studied in a multi-step approach using a self-built flow system capable of automatically controlling the liquid-handling and collecting data in real-time using a benchtop MS and NMR spectrometer. This study led to the identification of a transient Cu(I) species in situ which allows for the formation of dimeric and trimeric carbonato bridged Cu(II) assemblies. Furthermore, new Ni(II) complexes and more remarkably also a new binuclear Cu(I) complex, which usually requires long and laborious inert conditions, could be isolated. The study was then expanded to the autonomous optimization of the ligand synthesis by enabling feedback control on the chemical system via benchtop NMR. The synthesis of new polydentate ligands has emerged as a result of the study aiming to enhance the complexity of the chemical system to accelerate the discovery of new complexes. This type of ligand consists of 1-pyridinyl-4-imino-1,2,3-triazole units, which can coordinate with different metal salts. The studies to test for the CuAAC synthesis via microwave lead to the discovery of four new Cu complexes, one of them being a coordination polymer obtained from a solvent dependent crystallization technique. With the goal of easier integration into an automated system, copper tubing has been exploited as the chemical reactor for the synthesis of this ligand, as it efficiently enhances the rate of the triazole formation and consequently promotes the formation of the full ligand in high yields within two hours. Lastly, the digitization of coordination-driven self-assembly has been realized for the first time using an in-house autonomous chemical robot, herein named the ‘Finder’. The chemical parameter space to explore was defined by the selection of six variables, which consist of the ligand precursors necessary to form complex ligands (aldehydes, alkineamines and azides), of the metal salt solutions and of other reaction parameters – duration, temperature and reagent volumes. The platform was assembled using rounded bottom flasks, flow syringe pumps, copper tubing, as an active reactor, and in-line analytics – a pH meter probe, a UV-vis flow cell and a benchtop MS. The control over the system was then obtained with an algorithm capable of autonomously focusing the experiments on the most reactive region (by avoiding areas of low interest) of the chemical parameter space to explore. This study led to interesting observations, such as metal exchange phenomena, and also to the autonomous discovery of self assembled structures in solution and solid state – such as 1-pyridinyl-4-imino-1,2,3-triazole based Fe complexes and two helicates based on the same ligand coordination motif.

Validation of the Flexibility of Responses to Self-Critical Thoughts Scale (FoReST) in a clinical population

Background: The Flexibility of Responses to Self-Critical Thoughts Scale (FoReST) is a questionnaire that was developed to assess whether people can be psychologically flexible when experiencing critical thoughts about themselves. This measure could have important application for evaluating third wave therapies such as Acceptance and Commitment Therapy (ACT) and Compassion Focused therapy (CFT). This study investigated the validity (concurrent, predictive and incremental), internal consistency and factor structure of the FoReST in a sample of people experiencing mental health difficulties. Method: A total of 132 individuals attending Primary Care and Community Mental Health Teams within NHS Greater Glasgow and Clyde (NHS GGC) and Psychological Therapy Teams within NHS Lanarkshire participated in this study. Participants completed a battery of assessments that included the FoReST and related measures of similar constructs (psychological flexibility, self-compassion and self-criticism) and measures of mental health and well-being. A cross-sectional correlational design was used. Results: An Exploratory factor analysis described an interpretable 2-factor structure within the items of the FoReST: unworkable action and experiential avoidance. The FoReST demonstrated good internal consistency ( = .89). Concurrent validity was supported through moderate to strong correlations with similar measures and moderate correlations with other mental health and well-being outcomes. Conclusions: The FoReST appears to be a valid assessment measure for using with individuals experiencing mental health difficulties. This new measure will be of use for practitioners using ACT, CFT and those integrating both, to help monitor the process of change in flexibility and self-critical thinking across therapy. Further longitudinal studies are required to assess the test-retest reliability of the FoReST.