Lawesson's Reagent: Providing a New Approach to the Forgotten 6-Thioverdazyl Radical.

A new method for the preparation of the underrepresented 1,5-dimethyl-6-thioverdazyl radicals has been developed employing Lawesson's reagent (LR). The synthetic route involves the direct thionation of the carbonyl group of the corresponding dialkylbishydrazone followed by cyclization to give the tetrazinanthione verdazyl precursor on a gram scale. Subsequent oxidation yields the 6-thioverdazyl radical. It was determined that thionation of substrates containing electron-withdrawing groups in the ortho- or para-positions was high yielding. In contrast, for the parent phenyl group or substrates bearing weakly electron-donating substituents, thionation efficiency was significantly reduced. This could be overcome by utilizing partial in situ cyclization, which occurs during work up, to generate the tetrazinanthione directly via a one-pot synthesis. Density functional theory suggests that the LR fragment interacts with the carbonyl prior to cycloaddition and subsequent to cycloreversion, leading to the thiocarbonyl. The electronic nature of the radical is characterized with electron paramagnetic resonance as well as the first report of 6-thioverdazyl redox properties.

Factors associated with low fruit and vegetable consumption among people with severe mental ill health.

Severe mental ill health (SMI) is associated with excess mortality, and poor diet is one associated modifiable risk factor. This study investigated factors associated with low consumption of fruit and vegetables among people with SMI (N = 9914). A total of 8.4% of participants ate no portions per day, while only 15% ate 5 + portions. Individuals who never consumed fruit and vegetables or ate < 5 portions per day were more likely to be male, younger than 65, unemployed, experience poorer general health, or perceive health as unimportant. Poor diet is common among people with SMI and tailored dietary improvement interventions are required.

Tandem High-Pressure Crystallography-Optical Spectroscopy Unpacks Noncovalent Interactions of Piezochromic Fluorescent Molecular Rotors.

To develop luminescent molecular materials with predictable and stimuli-responsive emission, it is necessary to correlate changes in their geometries, packing structures, and noncovalent interactions with the associated changes in their optical properties. Here, we demonstrate that high-pressure single-crystal X-ray diffraction can be combined with high-pressure UV-visible absorption and fluorescence emission spectroscopies to elucidate how subtle changes in structure influence optical outputs. A piezochromic aggregation-induced emitter, sym-heptaphenylcycloheptatriene (Ph7C7H), displays bathochromic shifts in its absorption and emission spectra at high pressure. Parallel X-ray measurements identify the pressure-induced changes in specific phenyl-phenyl interactions responsible for the piezochromism. Pairs of phenyl rings from neighboring molecules approach the geometry of a stable benzene dimer, while conformational changes alter intramolecular phenyl-phenyl interactions correlated with a relaxed excited state. This tandem crystallographic and spectroscopic analysis provides insights into how subtle structural changes relate to the photophysical properties of Ph7C7H and could be applied to a library of similar compounds to provide general structure-property relationships in fluorescent organic molecules with rotor-like geometries.

High-pressure single-crystal diffraction at the Australian Synchrotron.

A new high-pressure single-crystal diffraction setup has been designed and implemented at the Australian Synchrotron for collecting molecular and protein crystal structures. The setup incorporates a modified micro-Merrill-Bassett cell and holder designed specifically to fit onto the horizontal air-bearing goniometer, allowing high-pressure diffraction measurements to be collected with little to no modification of the beamline setup compared with ambient data collections. Compression data for the amino acid, L-threonine, and the protein, hen egg-white lysozyme, were collected, showcasing the capabilities of the setup.

Adapting an online guided self-help intervention for the management of binge eating in adults with type 2 diabetes: The POSE-D study.

AIMS: People with type 2 diabetes (T2D) are more likely to experience binge eating than the general population, which may interfere with their diabetes management. Guided self-help (GSH) is the recommended treatment for binge-eating disorder, but there is currently a lack of evidenced treatment for binge eating in individuals living with T2D. The aims of the current study were to adapt an existing evidence-based GSH intervention using the principles of co-design to make it available online, suitable for remote delivery to address binge eating specifically in adults living with T2D. The Working to Overcome Eating Difficulties GSH intervention comprises online GSH materials presented in seven sections delivered over 12 weeks, supported by a trained Guide. METHODS: In order to adapt the intervention, we held four collaboration workshops with three expert patients recruited from diabetes support groups, eight healthcare professionals and an expert consensus group. We used thematic analysis to make sense of the data. RESULTS AND CONCLUSIONS: The main themes included; keeping the GSH material generic, adapting Sam the central character, tailoring the dietary advice and eating diary. The length of Guidance sessions was increased to 60 min, and Guide training was focussed around working with people with diabetes.

Impact of glycaemic technologies on quality of life and related outcomes in adults with type 1 diabetes: A narrative review.

AIMS: To explore the association between the use of glycaemic technologies and person-reported outcomes (PROs) in adults with type 1 diabetes (T1D). METHODS: We included T1D and technology publications reporting on PROs since 2014. Only randomised controlled trials and cohort studies that used validated PRO measures (PROMs) were considered. RESULTS: T1D studies reported on a broad range of validated PROMs, mainly as secondary outcome measures. Most studies examined continuous glucose monitoring (CGM), intermittently scanned CGM (isCGM), and the role of continuous subcutaneous insulin infusion (CSII), including sensor-augmented CSII and closed loop systems. Generally, studies demonstrated a positive impact of technology on hypoglycaemia-specific and diabetes-specific PROs, including reduced fear of hypoglycaemia and diabetes distress, and greater satisfaction with diabetes treatment. In contrast, generic PROMs (including measures of health/functional status, emotional well-being, depressive symptoms, and sleep quality) were less likely to demonstrate improvements associated with the use of glycaemic technologies. Several studies showed contradictory findings, which may relate to study design, population and length of follow-up. Differences in PRO findings were apparent between randomised controlled trials and cohort studies, which may be due to different populations studied and/or disparity between trial and real-world conditions. CONCLUSIONS: PROs are usually assessed as secondary outcomes in glycaemic technology studies. Hypoglycaemia-specific and diabetes-specific, but not generic, PROs show the benefits of glycaemic technologies, and deserve a more central role in future studies as well as routine clinical care.

Statistical agreement of gonioscopy performed as a puppy and as an adult in the Samoyed dog.

OBJECTIVE: To assess whether gonioscopy performed on Samoyed puppies (6-14 weeks of age) is a reliable predictor of their gonioscopy results as adults (>11 months of age). PROCEDURE: A retrospective medical record search was performed to identify Samoyed dogs that had undergone gonioscopy as a puppy (6-14 weeks of age). A second prospective gonioscopy examination was performed as an adult (>11 months of age) and the results were compared. Gonioscopy was assessed on two characteristics: percent of iridocorneal angle (ICA) unaffected by pectinate ligament abnormalities (PLA) and ICA width, with PLA results categorized into unaffected ( ≥ $$ \ge $$ 75% open), moderately affected (50%-74% open), and severely affected (<50% open) and the width categorized into wide, moderate, narrow, and closed groups. A multivariate model was created that considered factors such as PLA, angle width, sex, puppy age, neuter status, and time between examinations. RESULTS: The eyes of 77 Samoyed dogs (154 eyes) met inclusion criteria. When assessing PLA, 90% of dogs had the same categorization as a puppy and as an adult. When assessing ICA width, 53.2% of dogs had the same width classification as a puppy and as an adult. There is strong evidence that variation between puppy and adult results increases with time between examination (p = .03). CONCLUSION: Puppies unaffected by PLA and with a wide ICA angle, are likely to retain these features as adults. Selection of puppies with desirable gonioscopic traits may help breeders to choose dogs likely to retain these traits as adults for breeding. This may reduce the incidence of glaucoma in the breed. Puppy examinations should be performed in both eyes. Examination of adults prior to breeding remains prudent.

Improving programme-led and focused interventions for eating disorders: An experts' consensus statement-A UK perspective.

OBJECTIVE: Eating disorders are associated with significant illness burden and costs, yet access to evidence-based care is limited. Greater use of programme-led and focused interventions that are less resource-intensive might be part of the solution to this demand-capacity mismatch. METHOD: In October 2022, a group of predominantly UK-based clinical and academic researchers, charity representatives and people with lived experience convened to consider ways to improve access to, and efficacy of, programme-led and focused interventions for eating disorders in an attempt to bridge the demand-capacity gap. RESULTS: Several key recommendations were made across areas of research, policy, and practice. Of particular importance is the view that programme-led and focused interventions are suitable for a range of different eating disorder presentations across all ages, providing medical and psychiatric risk are closely monitored. The terminology used for these interventions should be carefully considered, so as not to imply that the treatment is suboptimal. CONCLUSIONS: Programme-led and focused interventions are a viable option to close the demand-capacity gap for eating disorder treatment and are particularly needed for children and young people. Work is urgently needed across sectors to evaluate and implement such interventions as a clinical and research priority.

Regulation of Multistep Spin Crossover Across Multiple Stimuli in a 2-D Framework Material.

We investigate the effects of a broad array of external stimuli on the structural, spin-crossover (SCO) properties and nature of the elastic interaction within the two-dimensional Hofmann framework material [Fe(cintrz)2Pd(CN)4]·guest (cintrz = N-cinnamalidene 4-amino-1,2,4-triazole; A·guest; guest = 3H2O, 2H2O, and Ø). This framework exhibits a delicate balance between ferro- and antiferro-elastic interaction characters; we show that manipulation of the pore contents across guests = 3H2O, 2H2O, and Ø can be exploited to regulate this balance. In A·3H2O, the dominant antiferroelastic interaction character between neighboring FeII sites sees the low-temperature persistence of the mixed spin-state species {HS-LS} for {Fe1-Fe2} (HS = high spin, LS = low spin). Elastic interaction strain is responsible for stabilizing the {HS-LS} state and can be overcome by three mechanisms: (1) partial (2H2O) or complete (Ø) guest removal, (2) irradiation via the reverse light-induced excited spin-state trapping (LIESST) effect (λ = 830 nm), and (3) the application of external hydrostatic pressure. Combining experimental data with elastic models presents a clear interpretation that while guest molecules cause a negative chemical pressure, they also have consequences for the elastic interactions between metals beyond the simple chemical pressure picture typically proposed.

Behavioural activation to prevent depression and loneliness among socially isolated older people with long-term conditions: The BASIL COVID-19 pilot randomised controlled trial.

BACKGROUND: Older adults, including those with long-term conditions (LTCs), are vulnerable to social isolation. They are likely to have become more socially isolated during the Coronavirus Disease 2019 (COVID-19) pandemic, often due to advice to "shield" to protect them from infection. This places them at particular risk of depression and loneliness. There is a need for brief scalable psychosocial interventions to mitigate the psychological impacts of social isolation. Behavioural activation (BA) is a credible candidate intervention, but a trial is needed. METHODS AND FINDINGS: We undertook an external pilot parallel randomised trial (ISRCTN94091479) designed to test recruitment, retention and engagement with, and the acceptability and preliminary effects of the intervention. Participants aged ≥65 years with 2 or more LTCs were recruited in primary care and randomised by computer and with concealed allocation between June and October 2020. BA was offered to intervention participants (n = 47), and control participants received usual primary care (n = 49). Assessment of outcome was made blind to treatment allocation. The primary outcome was depression severity (measured using the Patient Health Questionnaire 9 (PHQ-9)). We also measured health-related quality of life (measured by the Short Form (SF)-12v2 mental component scale (MCS) and physical component scale (PCS)), anxiety (measured by the Generalised Anxiety Disorder 7 (GAD-7)), perceived social and emotional loneliness (measured by the De Jong Gierveld Scale: 11-item loneliness scale). Outcome was measured at 1 and 3 months. The mean age of participants was aged 74 years (standard deviation (SD) 5.5) and they were mostly White (n = 92, 95.8%), and approximately two-thirds of the sample were female (n = 59, 61.5%). Remote recruitment was possible, and 45/47 (95.7%) randomised to the intervention completed 1 or more sessions (median 6 sessions) out of 8. A total of 90 (93.8%) completed the 1-month follow-up, and 86 (89.6%) completed the 3-month follow-up, with similar rates for control (1 month: 45/49 and 3 months 44/49) and intervention (1 month: 45/47and 3 months: 42/47) follow-up. Between-group comparisons were made using a confidence interval (CI) approach, and by adjusting for the covariate of interest at baseline. At 1 month (the primary clinical outcome point), the median number of completed sessions for people receiving the BA intervention was 3, and almost all participants were still receiving the BA intervention. The between-group comparison for the primary clinical outcome at 1 month was an adjusted between-group mean difference of -0.50 PHQ-9 points (95% CI -2.01 to 1.01), but only a small number of participants had completed the intervention at this point. At 3 months, the PHQ-9 adjusted mean difference (AMD) was 0.19 (95% CI -1.36 to 1.75). When we examined loneliness, the adjusted between-group difference in the De Jong Gierveld Loneliness Scale at 1 month was 0.28 (95% CI -0.51 to 1.06) and at 3 months -0.87 (95% CI -1.56 to -0.18), suggesting evidence of benefit of the intervention at this time point. For anxiety, the GAD adjusted between-group difference at 1 month was 0.20 (-1.33, 1.73) and at 3 months 0.31 (-1.08, 1.70). For the SF-12 (physical component score), the adjusted between-group difference at 1 month was 0.34 (-4.17, 4.85) and at 3 months 0.11 (-4.46, 4.67). For the SF-12 (mental component score), the adjusted between-group difference at 1 month was 1.91 (-2.64, 5.15) and at 3 months 1.26 (-2.64, 5.15). Participants who withdrew had minimal depressive symptoms at entry. There were no adverse events. The Behavioural Activation in Social Isolation (BASIL) study had 2 main limitations. First, we found that the intervention was still being delivered at the prespecified primary outcome point, and this fed into the design of the main trial where a primary outcome of 3 months is now collected. Second, this was a pilot trial and was not designed to test between-group differences with high levels of statistical power. Type 2 errors are likely to have occurred, and a larger trial is now underway to test for robust effects and replicate signals of effectiveness in important secondary outcomes such as loneliness. CONCLUSIONS: In this study, we observed that BA is a credible intervention to mitigate the psychological impacts of COVID-19 isolation for older adults. We demonstrated that it is feasible to undertake a trial of BA. The intervention can be delivered remotely and at scale, but should be reserved for older adults with evidence of depressive symptoms. The significant reduction in loneliness is unlikely to be a chance finding, and replication will be explored in a fully powered randomised controlled trial (RCT). TRIAL REGISTRATION: ISRCTN94091479.

Enhanced synthesis of oxo-verdazyl radicals bearing sterically-and electronically-diverse C3-substituents.

The synthetic viability of the hydrazine- and phosgene-free synthesis of 1,5-dimethyl oxo-verdazyl radicals has been improved via a detailed study investigating the influence of the aryl substituent on tetrazinanone ring formation. Although it is well established that functionalisation at the C3 position of the tetrazinanone ring does not influence the nature of the radical, it is crucial in applications development. The synthetic route involves a 4-step sequence: Schiff base condensation of a carbohydrazide with an arylaldehyde, alkylation, ring closure then subsequent oxidation to the radical. We found that the presence of strong electron-donating substituents and electron rich heterocycles, result in a significant reduction in yield during both the alkylation and ring closure steps. This can, in part, be alleviated by milder alkylation conditions and further substitution of the aryl group. In comparison, more facile formation of the tetrazine ring was observed with examples containing electron-withdrawing groups and with meta- or para-substitution. Density functional theory suggests that the ring closure proceeds via the formation of an ion pair. Electron paramagnetic resonance spectroscopy provides insight into the precise electronic structure of the radical with small variations in hyperfine coupling constants revealing subtle differences.

Guest Removal and External Pressure Variation Induce Spin Crossover in Halogen-Functionalized 2-D Hofmann Frameworks.

The effect of halogen functionalization on the spin crossover (SCO) properties of a family of 2-D Hofmann framework materials, [FeIIPd(CN)4(thioX)2]·2H2O (X = Cl and Br; thioCl = (E)-1-(5-chlorothiophen-2-yl)-N-(4H-1,2,4-triazol-4-yl)methanimine) and thioBr = (E)-1-(5-bromothiophen-2-yl)-N-(4H-1,2,4-triazol-4-yl)methanimine)), is reported. Inclusion of both the chloro- and bromo-functionalized ligands into the Hofmann-type frameworks (1Cl·2H2O and 2Br·2H2O) results in a blocking of spin-state transitions due to internal chemical pressure effects derived by the collective steric bulk of the halogen atoms and guest molecules. Cooperative one-step SCO transitions are revealed by either guest removal or the application of external physical pressure. Notably, removal of solvent water reveals a robust framework scaffold with only marginal variation between the solvated and desolvated structures (as investigated by powder and single crystal X-ray diffraction). Yet, one-step complete SCO transitions are revealed in 1Cl and 2Br with a transition temperature shift between the analogues due to various steric, structural, and electronic considerations. SCO can also be induced in the solvated species, 1Cl·2H2O and 2Br·2H2O, with the application of physical pressure, revealing a complete one-step SCO transition above 0.62 GPa (as investigated by magnetic susceptibility and single crystal X-ray diffraction measurements).

Street Medics: An innovative learning opportunity for UK medical students in a primary care outreach setting.

It is well known that recruitment into general practice (GP) is low, particularly in deprived areas. Undergraduate medical students are encouraged to learn about health inequalities.However, teaching on this area has been perceived by some as uninspiring. Innovative teaching opportunities can engage students but more research is needed regarding exposure to deprived inner-city settings. Street Medics is an extra-curricular, educational initiative which enables students to join GPs doing street-outreach work. The aim of the study was to understand what motivates undergraduate medical students to engage with Street Medics and the impact of the experience. Focus group data were collected and thematically analysed. Motivating factor themes: appetite to explore; previous exposure including observation of perceived sub-optimal care to marginalised patients; perceived lack of exposure personally and in undergraduate teaching. Experience and impact themes: increased understanding of social determinants of health; change in perception; influence on career intentions; desire to incorporate into curriculum. Opportunities like Street Medics can supplement the undergraduate curriculum and not only challenge students' perceptions of marginalised patients but also ignite their enthusiasm for pursuing GP. By understanding the factors driving students' engagement in innovative educational opportunities, effective methods can be shared across undergraduate courses.

Single-Crystal X-Ray Diffraction Study of Pressure and Temperature-Induced Spin Trapping in a Bistable Iron(II) Hofmann Framework.

High-pressure single-crystal X-ray diffraction has been used to trap both the low-spin (LS) and high-spin (HS) states of the iron(II) Hofmann spin crossover framework, [FeII (pdm)(H2 O)[Ag(CN)2 ]2 ⋅H2 O, under identical experimental conditions, allowing the structural changes arising from the spin-transition to be deconvoluted from previously reported thermal effects.

'Singing with your baby': an evaluation of group singing sessions for women admitted to a specialist mother-baby unit.

This paper reports on the acceptability, experience of participation and the immediate impact on maternal mood state of group singing sessions, introduced as a routine component of a mother-baby unit (MBU) treatment programme. Data was collected from 27 women who participated in the pilot programme. Results showed that implementation of a singing intervention in this setting is positively appraised by women and is associated with positive changes in self-reported mood state from pre- to post-session. Key facilitators and barriers to the success of the programme and directions for future research are discussed.

In silico and in vitro evaluation of exonic and intronic off-target effects form a critical element of therapeutic ASO gapmer optimization.

With many safety and technical limitations partly mitigated through chemical modifications, antisense oligonucleotides (ASOs) are gaining recognition as therapeutic entities. The increase in potency realized by 'third generation chemistries' may, however, simultaneously increase affinity to unintended targets with partial sequence complementarity. However, putative hybridization-dependent off-target effects (OTEs), a risk historically regarded as low, are not being adequately investigated. Here we show an unexpectedly high OTEs confirmation rate during screening of fully phosphorothioated (PS)-LNA gapmer ASOs designed against the BACH1 transcript. We demonstrate in vitro mRNA and protein knockdown of off-targets with a wide range of mismatch (MM) and gap patterns. Furthermore, with RNase H1 activity residing within the nucleus, hybridization predicted against intronic regions of pre-mRNAs was tested and confirmed. This dramatically increased ASO-binding landscape together with relatively high potency of such interactions translates into a considerable safety concern. We show here that with base pairing-driven target recognition it is possible to predict the putative off-targets and address the liability during lead design and optimization phases. Moreover, in silico analysis performed against both primary as well as spliced transcripts will be invaluable in elucidating the mechanism behind the hepatoxicity observed with some LNA-modified gapmers.

Effect of Collaborative Care vs Usual Care on Depressive Symptoms in Older Adults With Subthreshold Depression: The CASPER Randomized Clinical Trial.

Importance: There is little evidence to guide management of depressive symptoms in older people. Objective: To evaluate whether a collaborative care intervention can reduce depressive symptoms and prevent more severe depression in older people. Design, Setting, and Participants: Randomized clinical trial conducted from May 24, 2011, to November 14, 2014, in 32 primary care centers in the United Kingdom among 705 participants aged 65 years or older with Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) subthreshold depression; participants were followed up for 12 months. Interventions: Collaborative care (n=344) was coordinated by a case manager who assessed functional impairments relating to mood symptoms. Participants were offered behavioral activation and completed an average of 6 weekly sessions. The control group received usual primary care (n=361). Main Outcomes and Measures: The primary outcome was self-reported depression severity at 4-month follow-up on the 9-item Patient Health Questionnaire (PHQ-9; score range, 0-27). Included among 10 prespecified secondary outcomes were the PHQ-9 score at 12-month follow-up and the proportion meeting criteria for depressive disorder (PHQ-9 score ≥10) at 4- and 12-month follow-up. Results: The 705 participants were 58% female with a mean age of 77 (SD, 7.1) years. Four-month retention was 83%, with higher loss to follow-up in collaborative care (82/344 [24%]) vs usual care (37/361 [10%]). Collaborative care resulted in lower PHQ-9 scores vs usual care at 4-month follow-up (mean score with collaborative care, 5.36 vs with usual care, 6.67; mean difference, -1.31; 95% CI, -1.95 to -0.67; P < .001). Treatment differences remained at 12 months (mean PHQ-9 score with collaborative care, 5.93 vs with usual care, 7.25; mean difference, -1.33; 95% CI, -2.10 to -0.55). The proportions of participants meeting criteria for depression at 4-month follow-up were 17.2% (45/262) vs 23.5% (76/324), respectively (difference, -6.3% [95% CI, -12.8% to 0.2%]; relative risk, 0.83 [95% CI, 0.61-1.27]; P = .25) and at 12-month follow-up were 15.7% (37/235) vs 27.8% (79/284) (difference, -12.1% [95% CI, -19.1% to -5.1%]; relative risk, 0.65 [95% CI, 0.46-0.91]; P = .01). Conclusions and Relevance: Among older adults with subthreshold depression, collaborative care compared with usual care resulted in a statistically significant difference in depressive symptoms at 4-month follow-up, of uncertain clinical importance. Although differences persisted through 12 months, findings are limited by attrition, and further research is needed to assess longer-term efficacy. Trial Registration: isrctn.org Identifier: ISRCTN02202951.

Guided Self-help for Eating Disorders: A Systematic Review and Metaregression.

BACKGROUND: Evidence-based self-help is a recommended first stage of treatment for mild-moderate eating disorders. The provision of guidance enhances outcome. The literature evaluating exclusively 'guided' self-help (GSH) has not been systematically reviewed. METHODS: The aim was to establish the effectiveness of GSH for reducing global eating disorder psychopathology and abstinence from binge eating, compared with controls. Results were pooled using random effects meta-analysis and heterogeneity explored using metaregression. RESULTS: Thirty randomised controlled trials met the inclusion criteria. Results showed an overall effect of GSH on global eating disorder psychopathology (-0.46) and binge abstinence (-0.20). There was strong evidence for an association between diagnosis of binge eating disorder and binge abstinence. DISCUSSION: Current interventions need to be adapted to address features other than binge eating. Further research is required to help us understand the effectiveness of GSH in children and young people, invariably high dropout rates and how technology can enhance interventions. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Ligand effects on gas adsorption in nanoporous phthalocyanine crystals.

X-ray diffraction is used to study the sorption of CO and NO in two phthalocyanine nanoporous crystals (PNCs) with 4,4' bipyridine or 4,4' bipyrimidine trans coordinated to open Co2+ sites, demonstrating how the trans coordinated ligands influence the gas sorption properties and structures of the PNCs.

Putting the squeeze on valence tautomerism in cobalt-dioxolene complexes.

Molecules that can reversibly switch between electronic states under an external stimulus are of interest to numerous applications. Complexes of open shell metal ions with redox active ligands undergo valence tautomerism, resulting in magnetic, colour and structural switching, relevant to data storage and actuators. However, the precise structural changes occurring during valence tautomerism in the solid state are unclear due to the lack of atomic-resolution characterization. Here, variable temperature and high-pressure single crystal X-ray diffraction is used to characterize valence tautomerism in two isostructural cobalt complexes, [Co(bis(6-methyl-2-pyridylmethyl) amine)(3,5-di-tert-butyl-1,2-dioxolene)]+ and [Co(tris(6-methyl-2-pyridylmethyl)amine)(3,5-di-tert-butyl-1,2-dioxolene)]+ to atomic resolution. The less sterically hindered dimethylated complex exhibits two-step thermally-induced interconversion between the high-spin CoII-seminquinonate and low-spin CoIII-catecholate forms (valence tautomerism) at 155 and 95 K due to the presence of two symmetry-independent complexes. In contrast, the more sterically hindered trimethylated complex does not display thermal valence tautomerism. Both complexes exhibit unique behaviour under high pressure. The dimethylated species undergoes gradual, one-step valence tautomerism in both symmetry-independent complexes concurrently between 0.43 GPa and 1.30 GPa. In the trimethylated species, pressure is sufficient to overcome steric hindrance, leading to one-step valence tautomerism between 2.60 GPa and 3.10 GPa, demonstrating pressure-triggered valence tautomerism in a thermally inactive complex. This study is among the few investigations using in situ high-pressure single crystal X-ray diffraction to achieve atomic-level structural characterization of valence tautomerism, aiding the development of robust structure-property relationships in these types of complexes.