On the genetic basis of tail-loss evolution in humans and apes.

The loss of the tail is among the most notable anatomical changes to have occurred along the evolutionary lineage leading to humans and to the 'anthropomorphous apes'1-3, with a proposed role in contributing to human bipedalism4-6. Yet, the genetic mechanism that facilitated tail-loss evolution in hominoids remains unknown. Here we present evidence that an individual insertion of an Alu element in the genome of the hominoid ancestor may have contributed to tail-loss evolution. We demonstrate that this Alu element-inserted into an intron of the TBXT gene7-9-pairs with a neighbouring ancestral Alu element encoded in the reverse genomic orientation and leads to a hominoid-specific alternative splicing event. To study the effect of this splicing event, we generated multiple mouse models that express both full-length and exon-skipped isoforms of Tbxt, mimicking the expression pattern of its hominoid orthologue TBXT. Mice expressing both Tbxt isoforms exhibit a complete absence of the tail or a shortened tail depending on the relative abundance of Tbxt isoforms expressed at the embryonic tail bud. These results support the notion that the exon-skipped transcript is sufficient to induce a tail-loss phenotype. Moreover, mice expressing the exon-skipped Tbxt isoform develop neural tube defects, a condition that affects approximately 1 in 1,000 neonates in humans10. Thus, tail-loss evolution may have been associated with an adaptive cost of the potential for neural tube defects, which continue to affect human health today.

Establishing and maintaining Hox profiles during spinal cord development.

The chromosomally-arrayed Hox gene family plays central roles in embryonic patterning and the specification of cell identities throughout the animal kingdom. In vertebrates, the relatively large number of Hox genes and pervasive expression throughout the body has hindered understanding of their biological roles during differentiation. Studies on the subtype diversification of spinal motor neurons (MNs) have provided a tractable system to explore the function of Hox genes during differentiation, and have provided an entry point to explore how neuronal fate determinants contribute to motor circuit assembly. Recent work, using both in vitro and in vivo models of MN subtype differentiation, have revealed how patterning morphogens and regulation of chromatin structure determine cell-type specific programs of gene expression. These studies have not only shed light on basic mechanisms of rostrocaudal patterning in vertebrates, but also have illuminated mechanistic principles of gene regulation that likely operate in the development and maintenance of terminal fates in other systems.

Regulating Access to Active Sites via Hydrogen Bonding and Cation-Dipole Interactions: A Dual Cofactor Approach to Switchable Catalysis.

Hydrogen bonding networks are ubiquitous in biological systems and play a key role in controlling the conformational dynamics and allosteric interactions of enzymes. Yet in small organometallic catalysts, hydrogen bonding rarely controls ligand binding to the metal center. In this work, a hydrogen bonding network within a well-defined organometallic catalyst works in concert with cation-dipole interactions to gate substrate access to the active site. An ammine ligand acts as one cofactor, templating a hydrogen bonding network within a pendent crown ether and preventing the binding of strong donor ligands, such as nitriles, to the nickel center. Sodium ions are the second cofactor, disrupting hydrogen bonding to enable switchable ligand substitution reactions. Thermodynamic analyses provide insight into the energetic requirements of the different supramolecular interactions that enable substrate gating. The dual cofactor approach enables switchable catalytic hydroamination of crotononitrile. Systematic comparisons of catalysts with varying structural features provide support for the critical role of the dual cofactors in achieving on/off catalysis with substrates containing strongly donating functional groups that might otherwise interfere with switchable catalysts.

Highly Selective Electrochemical Baeyer-Villiger Oxidation through Oxygen Atom Transfer from Water.

The Baeyer-Villiger oxidation of ketones is a crucial oxygen atom transfer (OAT) process used for ester production. Traditionally, Baeyer-Villiger oxidation is accomplished by thermally oxidizing the OAT from stoichiometric peroxides, which are often difficult to handle. Electrochemical methods hold promise for breaking the limitation of using water as the oxygen atom source. Nevertheless, existing demonstrations of electrochemical Baeyer-Villiger oxidation face the challenges of low selectivity. We report in this study a strategy to overcome this challenge. By employing a well-known water oxidation catalyst, Fe2O3, we achieved nearly perfect selectivity for the electrochemical Baeyer-Villiger oxidation of cyclohexanone. Mechanistic studies suggest that it is essential to produce surface hydroperoxo intermediates (M-OOH, where M represents a metal center) that promote the nucleophilic attack on ketone substrates. By confining the reactions to the catalyst surfaces, competing reactions (e.g., dehydrogenation, carboxylic acid cation rearrangements, and hydroxylation) are greatly limited, thereby offering high selectivity. The surface-initiated nature of the reaction is confirmed by kinetic studies and spectroelectrochemical characterizations. This discovery adds nucleophilic oxidation to the toolbox of electrochemical organic synthesis.

Tunable and Switchable Catalysis Enabled by Cation-Controlled Gating with Crown Ether Ligands.

ConspectusCatalysis has become an essential tool in science and technology, impacting the discovery of pharmaceuticals, the manufacture of commodity chemicals and plastics, the production of fuels, and much more. In most cases, a particular catalyst is optimized to mediate a particular reaction, continually producing a desired product at a given rate. There is enormous opportunity in developing catalysts that are dynamic, capable of responding to a change in the environment to alter structure and function. Controlled catalysis, in which the activity or selectivity of a catalytic reaction can be adjusted through an external stimulus, offers opportunities for innovation in catalysis. Catalyst discovery could be simplified if a single thoughtfully designed complex could work synergistically with additives to optimize performance rather than trying a multitude of different metal/ligand combinations. Temporal control could be gained to facilitate the execution of multiple reactions in the same flask, for example, by activating one catalyst and deactivating another to avoid incompatibilities. Selectivity switching could enable copolymer synthesis with well-defined chemical and material properties. These applications might sound futuristic for synthetic catalysts, but in nature, such a degree of controlled catalysis is commonplace. For example, allosteric interactions and/or feedback loops modulate enzymatic activity to enable complex small-molecule synthesis and sequence-defined polymerization reactions in complex mixtures containing many catalytic sites. In many cases, regulation is achieved by "gating" substrate access to the active site. Fundamental advances in catalyst design are needed to better understand the factors that enable controlled catalysis in the arena of synthetic chemistry, particularly in achieving substrate gating outside of macromolecular environments. In this Account, the development of design principles for achieving cation-controlled catalysis is described. The guiding hypothesis was that gating substrate access to a catalyst site could be achieved by controlling the dynamics of a hemilabile ligand through secondary Lewis acid/base and/or cation-dipole interactions. To enforce such interactions, catalysts sitting at the interface of organometallic catalysis and supramolecular chemistry were designed. A macrocyclic crown ether was incorporated into a robust organometallic pincer ligand, and these "pincer-crown ether" ligands have been explored in catalysis. Complementary studies of controlled catalysis and detailed mechanistic analysis guided the development of iridium, nickel, and palladium pincer-crown ether catalysts capable of substrate gating. Toggling the gate between open and closed states leads to switchable catalysis, where cation addition/removal changes the turnover frequency or the product selectivity. Varying the degree of gating leads to tunable catalysis, where the activity can be tuned based on the identity and amount of salt added. Research has focused on reactions of alkenes, particularly isomerization reactions, which has in turn led to design principles for cation-controlled catalysts.

Kinetic Isotope Effects and the Mechanism of CO2 Insertion into the Metal-Hydride Bond of fac-(bpy)Re(CO)3H.

The 1,2-insertion reaction of CO2 into metal-hydride bonds of d6-octahedral complexes to give κ1-O-metal-formate products is the key step in various CO2 reduction schemes and as a result has attracted extensive mechanistic investigations. For many octahedral catalysts, CO2 insertion follows an associative mechanism in which CO2 interacts directly with the coordinated hydride ligand instead of the more classical dissociative mechanism that opens an empty coordination site to bind the substrate to the metal prior to a hydride migration step. To better understand the associative mechanism, we conducted a systematic quantum chemical investigation on the reaction between CO2 and fac-(bpy)Re(CO)3H (1-Re-H; bpy = 2,2'-bipyridine) starting with the gas phase and then moving to THF and other solvents with increased dielectric constants. Detailed analyses of the potential energy surfaces (PESs) and intrinsic reaction coordinates (IRCs) reveal that the reaction is enabled in all media by an initial stage of making a 3c-2e bond between the carbon of CO2 and the metal-hydride bond that is most consistent with an organometallic bridging hydride Re-H-CO2 species. Once CO2 is bent and anchored to the metal-hydride bond, the reaction proceeds by a rotation motion via a cyclic transition state TS2 that interchanges Re-H-CO2 and Re-O-CHO coordination. The combined stages provide an asynchronous-concerted pathway for CO2 insertion on the Gibbs free energy surface with TS2 as the highest energy point. Consideration of TS2 as a rate-determining TS gives activation barriers, inverse KIEs, substituent effects, and solvent effects that agree with the experimental data available in this system. An important new insight revealed by the analyses of the results is that the initial stage of the reaction is not a hydride transfer step as has been assumed in some studies. In fact, the loose vibration of the TS that can be identified for the first stage of the reaction in solution (TS1) does not involve the Re-H stretching vibrational mode. Accordingly, the imaginary frequency of TS1 is insensitive to deuteration, and therefore, TS1 leads to no significant KIE.

Updates on coding in dermatology.

Correct coding is an important component of effective dermatology practice management. Over the past several years there have been updates to many commonly used codes within dermatology. This review highlights many of these updates, such as: the skin biopsy codes have been subdivided to reflect the different biopsy techniques. The definition of complex linear repairs has been updated and clarified. Outpatient and inpatient evaluation and management visits have new coding guidelines to determine level of care. Dermatopathology consultation codes have been updated and category III codes related to digital pathology have been created. Understanding the details and nuances of each of these categories of codes is vital to ensuring appropriate coding is performed.

Lewis Structures and the Bonding Classification of End-on Bridging Dinitrogen Transition Metal Complexes.

The activation of dinitrogen by coordination to transition metal ions is a widely used and promising approach to the utilization of Earth's most abundant nitrogen source for chemical synthesis. End-on bridging N2 complexes (µ-η1:η1-N2) are key species in nitrogen fixation chemistry, but a lack of consensus on the seemingly simple task of assigning a Lewis structure for such complexes has prevented application of valence electron counting and other tools for understanding and predicting reactivity trends. The Lewis structures of bridging N2 complexes have traditionally been determined by comparing the experimentally observed NN distance to the bond lengths of free N2, diazene, and hydrazine. We introduce an alternative approach here and argue that the Lewis structure should be assigned based on the total π-bond order in the MNNM core (number of π-bonds), which derives from the character (bonding or antibonding) and occupancy of the delocalized π-symmetry molecular orbitals (π-MOs) in MNNM. To illustrate this approach, the complexes cis,cis-[(iPr4PONOP)MCl2]2(µ-N2) (M = W, Re, and Os) are examined in detail. Each complex is shown to have a different number of nitrogen-nitrogen and metal-nitrogen π-bonds, indicated as, respectively: W≡N-N≡W, Re═N═N═Re, and Os-N≡N-Os. It follows that each of these Lewis structures represents a distinct class of complexes (diazanyl, diazenyl, and dinitrogen, respectively), in which the µ-N2 ligand has a different electron donor number (total of 8e-, 6e-, or 4e-, respectively). We show how this classification can greatly aid in understanding and predicting the properties and reactivity patterns of µ-N2 complexes.

Non-randomized evaluation of hospitalization after a prescription for nirmatrelvir/ritonavir versus molnupiravir in high-risk COVID-19 outpatients.

OBJECTIVES: To assess and compare subsequent hospital admissions within 30 days for patients after receiving a prescription for either oral nirmatrelvir/ritonavir or oral molnupiravir. METHODS: We conducted a retrospective review of 3207 high-risk, non-hospitalized adult COVID-19 patients who received a prescription for molnupiravir (n = 209) or nirmatrelvir/ritonavir (n = 2998) at an academic medical centre in New York City from April to December 2022. Variables including age, vaccination status, high-risk conditions and demographic factors were pulled from the electronic medical record. We used multivariable logistic regression to adjust for potential confounding variables. RESULTS: All-cause 30 day hospitalization was not significantly different between patients who received nirmatrelvir/ritonavir compared with molnupiravir (1.4% versus 1.9%, P value = 0.55). The association between COVID-related hospitalization and medication was also not significant (0.7%versus 0.5%, P value = 0.99). Patients who received molnupiravir were more likely to have more underlying high-risk conditions. After adjusting for potential confounders, the odds of all-cause hospitalizations were not significantly different between patients who received nirmatrelvir/ritonavir compared with molnupiravir (OR = 1.16, 95% CI: 0.4-3.3, P value = 0.79). CONCLUSIONS: These data provide additional evidence to support molnupiravir as a suitable alternative when other COVID-19 antivirals cannot be given.

Ultrafast X-Ray Scattering Reveals Composite Amplitude Collective Mode in the Weyl Charge Density Wave Material (TaSe_{4})_{2}I.

We report ultrafast x-ray scattering experiments of the quasi-1D charge density wave (CDW) material (TaSe_{4})_{2}I following ultrafast infrared photoexcitation. From the time-dependent diffraction signal at the CDW sidebands we identify a 0.11 THz amplitude mode derived primarily from a transverse acoustic mode of the high-symmetry structure. From our measurements we determine that this mode interacts with the valence charge indirectly through another collective mode, and that the CDW system in (TaSe_{4})_{2}I has a composite nature supporting multiple dynamically active structural degrees of freedom.

Catalytic reduction of dinitrogen to ammonia using molybdenum porphyrin complexes.

Porphyrin complexes are well-known in O2 and CO2 reduction, but their application to N2 reduction is less developed. Here, we show that oxo and nitrido complexes of molybdenum supported by tetramesitylporphyrin (TMP) are effective precatalysts for catalytic N2 reduction to ammonia, verified by 15N2 labeling studies and other control experiments. Spectroscopic and electrochemical studies illuminate some relevant thermodynamic parameters, including the N-H bond dissociation free energy of (TMP)MoNH (43 ± 2 kcal mol-1). We place these results in the context of other work on homogeneous N2 reduction catalysis.

Oxidative Addition of a Phosphinite P-O Bond at Nickel.

Oxidative addition is an essential elementary reaction in organometallic chemistry and catalysis. While a diverse array of oxidative addition reactions has been reported to date, examples of P-O bond activation are surprisingly rare. Herein, we report the ligand-templated oxidative addition of a phosphinite P-O bond in the diphosphinito aniline compound HN(2-OPiPr2-3,5-tBu-C6H2)2 [H(P2ONO)] at Ni0 to form (PONO)Ni(HPiPr2) after proton rearrangement. Notably, the P-O cleavage occurs selectively over an amine N-H bond activation. Additionally, the ligand cannibalization is reversible, as addition of XPR2 (X = Cl, Br; R = iPr, Cy) to (PONO)Ni(HPiPr2) readily produces either symmetric or unsymmetric (P2ONO)NiX species and free HPiPr2. Finally, the mechanisms of both the initial P-O bond cleavage and its subsequent reconstruction are investigated to provide further insight into how to target P-O bond activation.

Making ends meet - relating a self-reported indicator of financial hardship to health status.

BACKGROUND: Area-based index of multiple deprivation (IMD) indicators of financial hardship lack individual specificity and sensitivity. This study compared self-reports of hardship with area measures in relation to health status. METHODS: Interviews in one London Borough, reported financial hardship and health status. Associations of health status with most and least deprived quintiles of the IMD 2015 were compared with self-reported hardship; always or sometimes 'having difficulty making ends meet at the end of the month' in relation to never. RESULTS: 1024 interviews reported hardship status in 1001 (98%). 392 people (39%) reported they 'always' or 'sometimes' had hardship. In multivariate analysis, self-reported hardship was more strongly associated with smoking; odds ratio = 5.4 (95% CI: 2.8-10.4) compared with IMD, odds ratio = 1.9 (95% CI: 1.2-3.2). Health impairment was also more likely with self-reported hardship, odds ratio = 11.1 (95% CI: 4.9-25.4) compared with IMD; odds ratio = 2.7 (95% CI: 1.4-5.3). Depression was similarly related; odds ratio = 2.4 (95% CI: 1.0-5.6) and 2.7 (95% CI: 1.2-6.6), respectively. CONCLUSIONS: Self-reported hardship was more strongly related to health status than area-based indicators. Validity and implementation in routine health care settings remains to be established.

Semi-Empirical Satellite-to-Ground Quantum Key Distribution Model for Realistic Receivers.

Satellite-based link analysis is valuable for efficient and secure quantum communication, despite seasonal limits and restrictions on transmission times. A semi-empirical quantum key distribution model for satellite-based systems was proposed that simplifies simulations of communication links. Unlike other theoretical models, our approach was based on the experimentally-determined atmospheric extinction coefficient typical for mid-latitude ground stations. The parameter was measured for both clear and foggy conditions, and it was validated using published experimental data from the Micius satellite. Using this model, we simulated secure QKD between the Micius satellite and ground stations with 300 mm and 600 mm aperture telescopes.

Using wearable technology to prevent pressure injuries: An integrative review.

BACKGROUND: Hospital-acquired pressure injuries (HAPIs) are a significant problem for hospitals worldwide, negatively affecting patients and organizations by decreasing quality of life and increasing organizational cost of care and workload. A common pressure injury prevention intervention is frequent turning, though compliance can be low. As a newer technology, wearable sensors have emerged as an intervention to increase turn compliance. AIMS: The aim of this integrative review was to determine the clinical outcomes of using wearable sensors as a HAPI prevention intervention. METHODS: This integrative review was appraised by two independent reviewers using the Johns Hopkins Nursing Evidence-Based Practice Research Appraisal Tool. RESULTS: Eleven articles were included. The use of wearable sensors increases compliance with frequent turn protocols while decreasing HAPIs and reducing organizational costs. Despite this, the use of such technology was not found to increase the quality of turns. Although staff who used this technology reported positive feedback, technological training is needed to ensure proper use of the sensors. LINKING ACTION TO PRACTICE: This innovation has the potential to transform how nursing staff prevent pressure injuries, but more research is needed to definitively state whether wearable sensors will be efficacious as a pressure injury prevention intervention.

Correlating Thermodynamic and Kinetic Hydricities of Rhenium Hydrides.

The kinetics of hydride transfer from Re(Rbpy)(CO)3H (bpy = 4,4'-R-2,2'-bipyridine; R = OMe, tBu, Me, H, Br, COOMe, CF3) to CO2 and seven different cationic N-heterocycles were determined. Additionally, the thermodynamic hydricities of complexes of the type Re(Rbpy)(CO)3H were established primarily using computational methods. Linear free-energy relationships (LFERs) derived by correlating thermodynamic and kinetic hydricities indicate that, in general, the rate of hydride transfer increases as the thermodynamic driving force for the reaction increases. Kinetic isotope effects range from inverse for hydride transfer reactions with a small driving force to normal for reactions with a large driving force. Hammett analysis indicates that hydride transfer reactions with greater thermodynamic driving force are less sensitive to changes in the electronic properties of the metal hydride, presumably because there is less buildup of charge in the increasingly early transition state. Bronsted α values were obtained for a range of hydride transfer reactions and along with DFT calculations suggest the reactions are concerted, which enables the use of Marcus theory to analyze hydride transfer reactions involving transition metal hydrides. It is notable, however, that even slight perturbations in the steric properties of the Re hydride or the hydride acceptor result in large deviations in the predicted rate of hydride transfer based on thermodynamic driving forces. This indicates that thermodynamic considerations alone cannot be used to predict the rate of hydride transfer, which has implications for catalyst design.

Older adults' willingness to take magnesium to treat depression.

Context: Depression affects up to 15% of community-dwelling older adults. Late-life depression is frequently underdiagnosed and undertreated. When depression in older adults is identified, up to 80% of treatment occurs in primary care. Currently available treatments have significant limitations (e.g., modest effectiveness, high costs, adverse effects, poor adherence, and social stigma), therefore additional treatment options are essential. Over the counter magnesium chloride is inexpensive, widely available, generally safe, well-absorbed, and was efficacious in prior studies, often within 2 weeks. Objective: To collect background information on magnesium supplement use and acceptability in older adults with a depression. Study Design: Online survey. Dataset: National sample. Population Studied: Adults 65 and older living in the United States currently experiencing symptoms of depression based on Patient Health Questionnaire (PHQ- 2) results. Outcome Measures: The primary outcome was willingness to take magnesium supplements instead of prescription medication for the treatment of depression. Secondary measures included current supplement use, comfort level with taking magnesium to treat depression, and whether they think magnesium would help improve symptoms of depression. Results: Of 153 respondents, 97 (63%) were female, 143 (93%) identified as white, and 130 (85%) were between the ages 65 and 75 years. 112 (73%) took a supplement daily, including 15 (10%) taking magnesium. 50 (33%) were currently being treated for depression. On a 4-point Likert scale ranging from "Strongly Agree" to "Strongly Disagree," 83% of respondents "Agreed" or "Strongly Agreed" in terms of their willingness to take magnesium instead of a prescription medication. A majority also "Agreed" or "Strongly Agreed" that they were willing (89%) and comfortable (89%) with taking magnesium to treat depression and also that it would improve symptoms of depression (73%). Women were more likely to agree with these statements (p<0.05), but there were no differences based on age or current treatment for depression. Conclusions: A majority of older community-dwelling adults are willing to take magnesium for the treatment of depression. Many adults are already taking at least 1 over the counter supplement daily. Further research is needed to determine the efficacy of magnesium supplements as an alternative treatment option in this population.

Mechanisms of Electrochemical N2 Splitting by a Molybdenum Pincer Complex.

Molybdenum complexes supported by tridentate pincer ligands are exceptional catalysts for dinitrogen fixation using chemical reductants, but little is known about their prospects for electrochemical reduction of dinitrogen. The viability of electrochemical N2 binding and splitting by a molybdenum(III) pincer complex, (pyPNP)MoBr3 (pyPNP = 2,6-bis(tBu2PCH2)-C5H3N)), is established in this work, providing a foundation for a detailed mechanistic study of electrode-driven formation of the nitride complex (pyPNP)Mo(N)Br. Electrochemical kinetic analysis, optical and vibrational spectroelectrochemical monitoring, and computational studies point to two concurrent reaction pathways: In the reaction-diffusion layer near the electrode surface, the molybdenum(III) precursor is reduced by 2e- and generates a bimetallic molybdenum(I) Mo2(µ-N2) species capable of N-N bond scission; and in the bulk solution away from the electrode surface, over-reduced molybdenum(0) species undergo chemical redox reactions via comproportionation to generate the same bimetallic molybdenum(I) species capable of N2 cleavage. The comproportionation reactions reveal the surprising intermediacy of dimolybdenum(0) complex trans,trans-[(pyPNP)Mo(N2)2](µ-N2) in N2 splitting pathways. The same "over-reduced" molybdenum(0) species was also found to cleave N2 upon addition of lutidinium, an acid frequently used in catalytic reduction of dinitrogen.

Stepwise Iodide-Free Methanol Carbonylation via Methyl Acetate Activation by Pincer Iridium Complexes.

Iodide is an essential promoter in the industrial production of acetic acid via methanol carbonylation, but it also contributes to reactor corrosion and catalyst deactivation. Here we report that iridium pincer complexes mediate the individual steps of methanol carbonylation to methyl acetate in the absence of methyl iodide or iodide salts. Iodide-free methylation is achieved under mild conditions by an aminophenylphosphinite pincer iridium(I) dinitrogen complex through net C-O oxidative addition of methyl acetate to produce an isolable methyliridium(III) acetate complex. Experimental and computational studies provide evidence for methylation via initial C-H bond activation followed by acetate migration, facilitated by amine hemilability. Subsequent CO insertion and reductive elimination in methanol solution produced methyl acetate and acetic acid. The net reaction is methanol carbonylation to acetic acid using methyl acetate as a promoter alongside conversion of an iridium dinitrogen complex to an iridium carbonyl complex. Kinetic studies of migratory insertion and reductive elimination reveal essential roles of the solvent methanol and distinct features of acetate and iodide anions that are relevant to the design of future catalysts for iodide-free carbonylation.

Temperature and Solvent Effects on H2 Splitting and Hydricity: Ramifications on CO2 Hydrogenation by a Rhenium Pincer Catalyst.

The catalytic hydrogenation of carbon dioxide holds immense promise for applications in sustainable fuel synthesis and hydrogen storage. Mechanistic studies that connect thermodynamic parameters with the kinetics of catalysis can provide new understanding and guide predictive design of improved catalysts. Reported here are thermochemical and kinetic analyses of a new pincer-ligated rhenium complex (tBuPOCOP)Re(CO)2 (tBuPOCOP = 2,6-bis(di-tert-butylphosphinito)phenyl) that catalyzes CO2 hydrogenation to formate with faster rates at lower temperatures. Because the catalyst follows the prototypical "outer sphere" hydrogenation mechanism, comprehensive studies of temperature and solvent effects on the H2 splitting and hydride transfer steps are expected to be relevant to many other catalysts. Strikingly large entropy associated with cleavage of H2 results in a strong temperature dependence on the concentration of [(tBuPOCOP)Re(CO)2H]- present during catalysis, which is further impacted by changing the solvent from toluene to tetrahydrofuran to acetonitrile. New methods for determining the hydricity of metal hydrides and formate at temperatures other than 298 K are developed, providing insight into how temperature can influence the favorability of hydride transfer during catalysis. These thermochemical insights guided the selection of conditions for CO2 hydrogenation to formate with high activity (up to 364 h-1 at 1 atm or 3330 h-1 at 20 atm of 1:1 H2:CO2). In cases where hydride transfer is the highest individual kinetic barrier, entropic contributions to outer sphere H2 splitting lead to a unique temperature dependence: catalytic activity increases as temperature decreases in tetrahydrofuran (200-fold increase upon cooling from 50 to 0 °C) and toluene (4-fold increase upon cooling from 100 to 50 °C). Ramifications on catalyst structure-function relationships are discussed, including comparisons between "outer sphere" mechanisms and "metal-ligand cooperation" mechanisms.