Controlled Carbon Dioxide Terpolymerizations to Deliver Toughened yet Recyclable Thermoplastics.

Using CO2 polycarbonates as engineering thermoplastics has been limited by their mechanical performances, particularly their brittleness. Poly(cyclohexene carbonate) (PCHC) has a high tensile strength (40 MPa) but is very brittle (elongation at break <3%), which limits both its processing and applications. Here, well-defined, high molar mass CO2 terpolymers are prepared from cyclohexene oxide (CHO), cyclopentene oxide (CPO), and CO2 by using a Zn(II)Mg(II) catalyst. In the catalysis, CHO and CPO show reactivity ratios of 1.53 and 0.08 with CO2, respectively; as such, the terpolymers have gradient structures. The poly(cyclohexene carbonate)-grad-poly(cyclopentene carbonate) (PCHC-grad-PCPC) have high molar masses (86 < Mn < 164 kg mol-1, DM < 1.22) and good thermal stability (Td > 250 °C). All the polymers are amorphous with a single, high glass transition temperature (96 < Tg < 108 °C). The polymer entanglement molar masses, determined using dynamic mechanical analyses, range from 4 < Me < 23 kg mol-1 depending on the polymer composition (PCHC:PCPC). These polymers show superior mechanical performance to PCHC; specifically the lead material (PCHC0.28-grad-PCPC0.72) shows 25% greater tensile strength and 160% higher tensile toughness. These new plastics are recycled, using cycles of reprocessing by compression molding (150 °C, 1.2 ton m-2, 60 min), four times without any loss in mechanical properties. They are also efficiently chemically recycled to selectively yield the two epoxide monomers, CHO and CPO, as well as carbon dioxide, with high activity (TOF = 270-1653 h-1, 140 °C, 120 min). The isolated recycled monomers are repolymerized to form thermoplastic showing the same material properties. The findings highlight the benefits of the terpolymer strategy to deliver thermoplastics combining the beneficial low entanglement molar mass, high glass transition temperatures, and tensile strengths; PCHC properties are significantly improved by incorporating small quantities (23 mol %) of cyclopentene carbonate linkages. The general strategy of designing terpolymers to include chain segments of low entanglement molar mass may help to toughen other brittle and renewably sourced plastics.

Quantifying CO2 Insertion Equilibria for Low-Pressure Propene Oxide and Carbon Dioxide Ring Opening Copolymerization Catalysts.

While outstanding catalysts are known for the ring-opening copolymerization (ROCOP) of CO2 and propene oxide (PO), few are reported at low CO2 pressure. Here, a new series of Co(III)M(I) heterodinuclear catalysts are compared. The Co(III)K(I) complex shows the best activity (TOF = 1728 h-1) and selectivity (>90% polymer, >99% CO2) and is highly effective at low pressures (<10 bar). CO2 insertion is a prerate determining chemical equilibrium step. At low pressures, the concentration of the active catalyst depends on CO2 pressure; above 12 bar, its concentration is saturated, and rates are independent of pressure, allowing the equilibrium constant to be quantified for the first time (Keq = 1.27 M-1). A unified rate law, applicable under all operating conditions, is presented. As proof of potential, published data for leading literature catalysts are reinterpreted and the CO2 equilibrium constants estimated, showing that this unified rate law applies to other systems.

High Molar Mass Polycarbonates as Closed-Loop Recyclable Thermoplastics.

Using carbon dioxide (CO2) to make recyclable thermoplastics could reduce greenhouse gas emissions associated with polymer manufacturing. CO2/cyclic epoxide ring-opening copolymerization (ROCOP) allows for >30 wt % of the polycarbonate to derive from CO2; so far, the field has largely focused on oligocarbonates. In contrast, efficient catalysts for high molar mass polycarbonates are underinvestigated, and the resulting thermoplastic structure-property relationships, processing, and recycling need to be elucidated. This work describes a new organometallic Mg(II)Co(II) catalyst that combines high productivity, low loading tolerance, and the highest polymerization control to yield polycarbonates with number average molecular weight (Mn) values from 4 to 130 kg mol-1, with narrow, monomodal distributions. It is used in the ROCOP of CO2 with bicyclic epoxides to produce a series of samples, each with Mn > 100 kg mol-1, of poly(cyclohexene carbonate) (PCHC), poly(vinyl-cyclohexene carbonate) (PvCHC), poly(ethyl-cyclohexene carbonate) (PeCHC, by hydrogenation of PvCHC), and poly(cyclopentene carbonate) (PCPC). All these materials are amorphous thermoplastics, with high glass transition temperatures (85 < Tg < 126 °C, by differential scanning calorimetry) and high thermal stability (Td > 260 °C). The cyclic ring substituents mediate the materials' chain entanglements, viscosity, and glass transition temperatures. Specifically, PCPC was found to have 10× lower entanglement molecular weight (Me)n and 100× lower zero-shear viscosity compared to those of PCHC, showing potential as a future thermoplastic. All these high molecular weight polymers are fully recyclable, either by reprocessing or by using the Mg(II)Co(II) catalyst for highly selective depolymerizations to epoxides and CO2. PCPC shows the fastest depolymerization rates, achieving an activity of 2500 h-1 and >99% selectivity for cyclopentene oxide and CO2.

Kinetic Model for the Heterogeneous Biocatalytic Reactions Using Tethered Cofactors.

Understanding the mechanism of interfacial enzyme kinetics is critical to the development of synthetic biological systems for the production of value-added chemicals. Here, the interfacial kinetics of the catalysis of ß-nicotinamide adenine dinucleotide (NAD+)-dependent enzymes acting on NAD+ tethered to the surface of silica nanoparticles (SiNPs) has been investigated using two complementary and supporting kinetic approaches: enzyme excess and reactant (NAD+) excess. Kinetic models developed for these two approaches characterize several critical reaction steps including reversible enzyme adsorption, complexation, decomplexation, and catalysis of the surface-bound enzyme/NAD+ complex. The analysis reveals a concentrating effect resulting in a very high local concentration of enzyme and cofactor on the particle surface, in which the enzyme is saturated by surface-bound NAD, facilitating a rate enhancement of enzyme/NAD+ complexation and catalysis. This resulted in high enzyme efficiency within the tethered NAD+ system compared to that of the free enzyme/NAD+ system, which increases with decreasing enzyme concentration. The role of enzyme adsorption onto solid substrates with a tethered catalyst (such as NAD+) has potential for creating highly efficient flow biocatalytic systems.

Exploiting Organometallic Chemistry to Functionalize Small Cuprous Oxide Colloidal Nanocrystals.

The ligand chemistry of colloidal semiconductor nanocrystals mediates their solubility, band gap, and surface facets. Here, selective organometallic chemistry is used to prepare small, colloidal cuprous oxide nanocrystals and to control their surface chemistry by decorating them with metal complexes. The strategy is demonstrated using small (3-6 nm) cuprous oxide (Cu2O) colloidal nanocrystals (NC), soluble in organic solvents. Organometallic complexes are coordinated by reacting the surface Cu-OH bonds with organometallic reagents, M(C6F5)2, M = Zn(II) and Co(II), at room temperature. These reactions do not disrupt the Cu2O crystallinity or nanoparticle size; rather, they allow for the selective coordination of a specific metal complex at the surface. Subsequently, the surface-coordinated organometallic complex is reacted with three different carboxylic acids to deliver Cu-O-Zn(O2CR') complexes. Selective nanocrystal surface functionalization is established using spectroscopy (IR, 19F NMR), thermal gravimetric analyses (TGA), transmission electron microscopy (TEM, EELS), and X-ray photoelectron spectroscopy (XPS). Photoluminescence efficiency increases dramatically upon organometallic surface functionalization relative to that of the parent Cu2O NC, with the effect being most pronounced for Zn(II) decoration. The nanocrystal surfaces are selectively functionalized by both organic ligands and well-defined organometallic complexes; this synthetic strategy may be applicable to many other metal oxides, hydroxides, and semiconductors. In the future, it should allow NC properties to be designed for applications including catalysis, sensing, electronics, and quantum technologies.

Alternatives to fluorinated binders: recyclable copolyester/carbonate electrolytes for high-capacity solid composite cathodes.

Optimising the composite cathode for next-generation, safe solid-state batteries with inorganic solid electrolytes remains a key challenge towards commercialisation and cell performance. Tackling this issue requires the design of suitable polymer binders for electrode processability and long-term solid-solid interfacial stability. Here, block-polyester/carbonates are systematically designed as Li-ion conducting, high-voltage stable binders for cathode composites comprising of single-crystal LiNi0.8Mn0.1Co0.1O2 cathodes, Li6PS5Cl solid electrolyte and carbon nanofibres. Compared to traditional fluorinated polymer binders, improved discharge capacities (186 mA h g-1) and capacity retention (96.7% over 200 cycles) are achieved. The nature of the new binder electrolytes also enables its separation and complete recycling after use. ABA- and AB-polymeric architectures are compared where the A-blocks are mechanical modifiers, and the B-block facilitates Li-ion transport. This reveals that the conductivity and mechanical properties of the ABA-type are more suited for binder application. Further, catalysed switching between CO2/epoxide A-polycarbonate (PC) synthesis and B-poly(carbonate-r-ester) formation employing caprolactone (CL) and trimethylene carbonate (TMC) identifies an optimal molar mass (50 kg mol-1) and composition (wPC 0.35). This polymer electrolyte binder shows impressive oxidative stability (5.2 V), suitable ionic conductivity (2.2 × 10-4 S cm-1 at 60 °C), and compliant viscoelastic properties for fabrication into high-performance solid composite cathodes. This work presents an attractive route to optimising polymer binder properties using controlled polymerisation strategies combining cyclic monomer (CL, TMC) ring-opening polymerisation and epoxide/CO2 ring-opening copolymerisation. It should also prompt further examination of polycarbonate/ester-based materials with today's most relevant yet demanding high-voltage cathodes and sensitive sulfide-based solid electrolytes.

Al(III)/K(I) Heterodinuclear Polymerization Catalysts Showing Fast Rates and High Selectivity for Polyester Polyols.

Low molar mass, hydroxyl end-capped polymers, often termed "polyols," are widely used to make polyurethanes, resins, and coatings and as surfactants in liquid formulations. Epoxide/anhydride ring-opening copolymerization (ROCOP) is a controlled polymerization route to make them, and its viability depends upon catalyst selection. In the catalysis, the polyester polyol molar masses and end-groups are controlled by adding specific but excess quantities of diols (vs catalyst), known as the chain transfer agent (CTA), to the polymerizations, but many of the best current catalysts are inhibited or even deactivated by alcohols. Herein, a series of air-stable Al(III)/K(I) heterodinuclear polymerization catalysts show rates and selectivity at the upper end of the field. They also show remarkable increases in activity, with good selectivity and control, as quantities of diol are increased from 10-400 equiv. The reactions are accelerated by alcohols, and simultaneously, their use allows for the production of hydroxy telechelic poly/oligoesters (400 < Mn (g mol-1) < 20,400, D < 1.19). For example, cyclohexene oxide (CHO)/phthalic anhydride (PA) ROCOP, using the best Al(III)/K(I) catalyst with 200 equiv of diol, shows a turnover frequency (TOF) of 1890 h-1, which is 4.4× higher than equivalent reactions without any diol (Catalyst/Diol/PA/CHO = 1:10-400:400:2000, 100 °C). In all cases, the catalysis is well controlled and highly ester linkage selective (ester linkages >99%) and operates effectively using bicyclic and/or biobased anhydrides with bicyclic or flexible alkylene epoxides. These catalysts are recommended for future production and application development using polyester polyols.

Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients.

Viral clearance, antibody response and the mutagenic effect of molnupiravir has not been elucidated in at-risk populations. Non-hospitalised participants within 5 days of SARS-CoV-2 symptoms randomised to receive molnupiravir (n = 253) or Usual Care (n = 324) were recruited to study viral and antibody dynamics and the effect of molnupiravir on viral whole genome sequence from 1437 viral genomes. Molnupiravir accelerates viral load decline, but virus is detectable by Day 5 in most cases. At Day 14 (9 days post-treatment), molnupiravir is associated with significantly higher viral persistence and significantly lower anti-SARS-CoV-2 spike antibody titres compared to Usual Care. Serial sequencing reveals increased mutagenesis with molnupiravir treatment. Persistence of detectable viral RNA at Day 14 in the molnupiravir group is associated with higher transition mutations following treatment cessation. Viral viability at Day 14 is similar in both groups with post-molnupiravir treated samples cultured up to 9 days post cessation of treatment. The current 5-day molnupiravir course is too short. Longer courses should be tested to reduce the risk of potentially transmissible molnupiravir-mutated variants being generated. Trial registration: ISRCTN30448031.

Persistent low-level variants in a subset of viral genes are highly predictive of poor outcome in immunocompromised patients with cytomegalovirus infection.

BACKGROUND: Human cytomegalovirus is the most common and serious opportunistic infection after solid organ and haematopoietic stem cell transplantation. In this study, we used whole-genome cytomegalovirus data to investigate viral factors associated with the clinical outcome. METHODS: We sequenced cytomegalovirus samples from 16 immunocompromised paediatric patients with persistent viraemia. 8/16 patients died of complications due to cytomegalovirus infection. We also sequenced samples from 35 infected solid organ adult recipients of whom one died with cytomegalovirus infection. RESULTS: We showed that samples from both groups have fixed variants at resistance sites and mixed infections. NGS sequencing also revealed non-fixed variants at resistance sites in most of the patients who died (6/9). A machine learning approach identified 10 genes with non-fixed variants in these patients. These genes formed a viral signature which discriminated patients with cytomegalovirus infection who died from those that survived with high accuracy (AUC=0.96). Lymphocyte numbers for a subset of patients showed no recovery post-transplant in the patients who died. CONCLUSIONS: We hypothesise that the viral signature identified in this study may be a useful biomarker for poor response to antiviral drug treatment and indirectly for poor T cell function, potentially identifying early, those patients requiring non-pharmacological interventions.

Designing a circular carbon and plastics economy for a sustainable future.

The linear production and consumption of plastics today is unsustainable. It creates large amounts of unnecessary and mismanaged waste, pollution and carbon dioxide emissions, undermining global climate targets and the Sustainable Development Goals. This Perspective provides an integrated technological, economic and legal view on how to deliver a circular carbon and plastics economy that minimizes carbon dioxide emissions. Different pathways that maximize recirculation of carbon (dioxide) between plastics waste and feedstocks are outlined, including mechanical, chemical and biological recycling, and those involving the use of biomass and carbon dioxide. Four future scenarios are described, only one of which achieves sufficient greenhouse gas savings in line with global climate targets. Such a bold system change requires 50% reduction in future plastic demand, complete phase-out of fossil-derived plastics, 95% recycling rates of retrievable plastics and use of renewable energy. It is hard to overstate the challenge of achieving this goal. We therefore present a roadmap outlining the scale and timing of the economic and legal interventions that could possibly support this. Assessing the service lifespan and recoverability of plastic products, along with considerations of sufficiency and smart design, can moreover provide design principles to guide future manufacturing, use and disposal of plastics.

Oral nanotherapeutic formulation of insulin with reduced episodes of hypoglycaemia.

Injectable insulin is an extensively used medication with potential life-threatening hypoglycaemic events. Here we report on insulin-conjugated silver sulfide quantum dots coated with a chitosan/glucose polymer to produce a responsive oral insulin nanoformulation. This formulation is pH responsive, is insoluble in acidic environments and shows increased absorption in human duodenum explants and Caenorhabditis elegans at neutral pH. The formulation is sensitive to glucosidase enzymes to trigger insulin release. It is found that the formulation distributes to the liver in mice and rats after oral administration and promotes a dose-dependent reduction in blood glucose without promoting hypoglycaemia or weight gain in diabetic rodents. Non-diabetic baboons also show a dose-dependent reduction in blood glucose. No biochemical or haematological toxicity or adverse events were observed in mice, rats and non-human primates. The formulation demonstrates the potential to orally control blood glucose without hypoglycaemic episodes.

Evaluating Heterodinuclear Mg(II)M(II) (M = Mn, Fe, Ni, Cu, and Zn) Catalysts for the Chemical Recycling of Poly(cyclohexene carbonate).

Polymer chemical recycling to monomers (CRM) is important to help achieve a circular plastic economy, but the "rules" governing catalyst design for such processes remain unclear. Here, carbon dioxide-derived polycarbonates undergo CRM to produce epoxides and carbon dioxide. A series of dinuclear catalysts, Mg(II)M(II) where M(II) = Mg, Mn, Fe, Co, Ni, Cu, and Zn, are compared for poly(cyclohexene carbonate) depolymerizations. The recycling is conducted in the solid state, at 140 °C monitored using thermal gravimetric analyses, or performed at larger-scale using laboratory glassware. The most active catalysts are, in order of decreasing rate, Mg(II)Co(II), Mg(II)Ni(II), and Mg(II)Zn(II), with the highest activity reaching 8100 h-1 and with >99% selectivity for cyclohexene oxide. Both the activity and selectivity values are the highest yet reported in this field, and the catalysts operate at low loadings and moderate temperatures (from 1:300 to 1:5000, 140 °C). For the best heterodinuclear catalysts, the depolymerization kinetics and activation barriers are determined. The rates in both reverse depolymerization and forward CHO/CO2 polymerization catalysis show broadly similar trends, but the processes feature different intermediates; forward polymerization depends upon a metal-carbonate intermediate, while reverse depolymerization depends upon a metal-alkoxide intermediate. These dinuclear catalysts are attractive for the chemical recycling of carbon dioxide-derived plastics and should be prioritized for recycling of other oxygenated polymers and copolymers, including polyesters and polyethers. This work provides insights into the factors controlling depolymerization catalysis and steers future recycling catalyst design toward exploitation of lightweight and abundant s-block metals, such as Mg(II).

Within-host diversity improves phylogenetic and transmission reconstruction of SARS-CoV-2 outbreaks.

Accurate inference of who infected whom in an infectious disease outbreak is critical for the delivery of effective infection prevention and control. The increased resolution of pathogen whole-genome sequencing has significantly improved our ability to infer transmission events. Despite this, transmission inference often remains limited by the lack of genomic variation between the source case and infected contacts. Although within-host genetic diversity is common among a wide variety of pathogens, conventional whole-genome sequencing phylogenetic approaches exclusively use consensus sequences, which consider only the most prevalent nucleotide at each position and therefore fail to capture low-frequency variation within samples. We hypothesized that including within-sample variation in a phylogenetic model would help to identify who infected whom in instances in which this was previously impossible. Using whole-genome sequences from SARS-CoV-2 multi-institutional outbreaks as an example, we show how within-sample diversity is partially maintained among repeated serial samples from the same host, it can transmitted between those cases with known epidemiological links, and how this improves phylogenetic inference and our understanding of who infected whom. Our technique is applicable to other infectious diseases and has immediate clinical utility in infection prevention and control.

During an infectious disease outbreak, tracing who infected whom allows public health scientists to see how a pathogen is spreading and to establish effective control measures. Traditionally, this involves identifying the individuals an infected person comes into contact with and monitoring whether they also become unwell. However, this information is not always available and can be inaccurate. One alternative is to track the genetic data of pathogens as they spread. Over time, pathogens accumulate mutations in their genes that can be used to distinguish them from one another. Genetically similar pathogens are more likely to have spread during the same outbreak, while genetically dissimilar pathogens may have come from different outbreaks. However, there are limitations to this approach. For example, some pathogens accumulate genetic mutations very slowly and may not change enough during an outbreak to be distinguishable from one another. Additionally, some pathogens can spread rapidly, leaving less time for mutations to occur between transmission events. To overcome these challenges, Torres Ortiz et al. developed a more sensitive approach to pathogen genetic testing that took advantage of the multiple pathogen populations that often coexist in an infected patient. Rather than tracking only the most dominant genetic version of the pathogen, this method also looked at the less dominant ones. Torres Ortiz et al. performed genome sequencing of SARS-CoV-2 (the virus that causes COVID-19) samples from 451 healthcare workers, patients, and patient contacts at participating London hospitals. Analysis showed that it was possible to detect multiple genetic populations of the virus within individual patients. These subpopulations were often more similar in patients that had been in contact with one another than in those that had not. Tracking the genetic data of all viral populations enabled Torres Ortiz et al. to trace transmission more accurately than if only the dominant population was used. More accurate genetic tracing could help public health scientists better track pathogen transmission and control outbreaks. This may be especially beneficial in hospital settings where outbreaks can be smaller, and it is important to understand if transmission is occurring within the hospital or if the pathogen is imported from the community. Further research will help scientists understand how pathogen population genetics evolve during outbreaks and may improve the detection of subpopulations present at very low frequencies.

Chemical Recycling of Commercial Poly(l-lactic acid) to l-Lactide Using a High-Performance Sn(II)/Alcohol Catalyst System.

Poly(l-lactic acid) (PLLA) is a leading commercial polymer produced from biomass, showing useful properties for plastics and fiber applications; after use, it is compostable. One area for improvement is postconsumer waste PLLA chemical recycling to monomer (CRM), i.e., the formation of l-lactide (l-LA) from waste plastic. This process is currently feasible at high reaction temperatures and shows low catalytic activity accompanied, in some cases, by side reactions, including epimerization. Here, a commercial Sn(II) catalyst, applied with nonvolatile commercial alcohol, enables highly efficient CRM of PLLA to yield l-LA in excellent yield and purity (92% yield, >99% l-LA from theoretical max.). The depolymerization is performed using neat polymer films at low temperatures (160 °C) under a nitrogen flow or vacuum. The chemical recycling operates with outstanding activity, achieving turnover frequencies which are up to 3000× higher than previously excellent catalysts and applied at loadings up to 6000× lower than previously leading catalysts. The catalyst system achieves a TOF = 3000 h-1 at 0.01 mol % or 1:10,000 catalyst:PLLA loading. The depolymerization of waste PLLA plastic packaging (coffee cup lids) produces pure l-LA in excellent yield and selectivity. The new catalyst system (Sn + alcohol) can itself be recycled four times in different PLLA "batch degradations" and maintains its high catalytic productivity, activity, and selectivity.

Transient non-coeliac gluten sensitivity (NCGS) with markedly reduced villous height/crypt depth ratio.

There is no confident evidence in the current literature to show or demonstrate that non-coeliac gluten sensitivity (NCGS) exclusively presents with mild or nearly normal duodenal mucosal abnormality. Gluten sensitive patients with negative serology and severe mucosal changes are labelled with the term seronegative coeliac disease (SNCS). There might be at least some overlap between NCGS and SNCD. Transient gluten sensitivity with severe mucosal changes without CD have been previously reported like in our case.

Understanding catalytic synergy in dinuclear polymerization catalysts for sustainable polymers.

Understanding the chemistry underpinning intermetallic synergy and the discovery of generally applicable structure-performances relationships are major challenges in catalysis. Additionally, high-performance catalysts using earth-abundant, non-toxic and inexpensive elements must be prioritised. Here, a series of heterodinuclear catalysts of the form Co(III)M(I/II), where M(I/II) = Na(I), K(I), Ca(II), Sr(II), Ba(II) are evaluated for three different polymerizations, by assessment of rate constants, turn over frequencies, polymer selectivity and control. This allows for comparisons of performances both within and between catalysts containing Group I and II metals for CO2/propene oxide ring-opening copolymerization (ROCOP), propene oxide/phthalic anhydride ROCOP and lactide ring-opening polymerization (ROP). The data reveal new structure-performance correlations that apply across all the different polymerizations: catalysts featuring s-block metals of lower Lewis acidity show higher rates and selectivity. The epoxide/heterocumulene ROCOPs both show exponential activity increases (vs. Lewis acidity, measured by the pKa of [M(OH2)m]n+), whilst the lactide ROP activity and CO2/epoxide selectivity show linear increases. Such clear structure-activity/selectivity correlations are very unusual, yet are fully rationalised by the polymerization mechanisms and the chemistry of the catalytic intermediates. The general applicability across three different polymerizations is significant for future exploitation of catalytic synergy and provides a framework to improve other catalysts.

Correlating Metal Redox Potentials to Co(III)K(I) Catalyst Performances in Carbon Dioxide and Propene Oxide Ring Opening Copolymerization.

Carbon dioxide copolymerization is a front-runner CO2 utilization strategy but its viability depends on improving the catalysis. So far, catalyst structure-performance correlations have not been straightforward, limiting the ability to predict how to improve both catalytic activity and selectivity. Here, a simple measure of a catalyst ground-state parameter, metal reduction potential, directly correlates with both polymerization activity and selectivity. It is applied to compare performances of 6 new heterodinuclear Co(III)K(I) catalysts for propene oxide (PO)/CO2 ring opening copolymerization (ROCOP) producing poly(propene carbonate) (PPC). The best catalyst shows an excellent turnover frequency of 389 h-1 and high PPC selectivity of >99 % (50 °C, 20 bar, 0.025 mol% catalyst). As demonstration of its utility, neither DFT calculations nor ligand Hammett parameter analyses are viable predictors. It is proposed that the cobalt redox potential informs upon the active site electron density with a more electron rich cobalt centre showing better performances. The method may be widely applicable and is recommended to guide future catalyst discovery for other (co)polymerizations and carbon dioxide utilizations.