Use of Postpartum Hemorrhage Checklist during Vaginal Deliveries: A Quality Improvement Study.

OBJECTIVE: Postpartum hemorrhage (PPH) protocols improve patient safety and reduce utilization of blood products; however, few data exist on sustainability of PPH checklist use, how use affects care delivery, and variation of use among patient subgroups. This study aimed to (1) examine compliance with PPH checklist use during vaginal deliveries, (2) evaluate whether checklist use varied by patient and/or care team characteristics, and (3) evaluate whether checklist use was associated with increased use of recommended medications/interventions. STUDY DESIGN: This was a quality improvement study performed from April 2021 through June 2023. A multidisciplinary team developed a revised PPH checklist and used quality improvement methodology to increase checklist use following vaginal birth. Data were collected from medical records and clinician survey. Control charts were generated to track checklist use and evaluate special cause variation. Chi-square tests and logistic regression were used to evaluate variation in medications/interventions and across subgroups. RESULTS: During the study period, there were 342 cases of PPH at the time of vaginal birth. The checklist was used in 67% of PPH cases during the 20-month period after implementation in a setting where no checklist was previously being used. We found no statistically significant differences in checklist use by patient or health care team characteristics. Use of tranexamic acid, carboprost, and misoprostol were significantly associated with checklist use. CONCLUSION: This study demonstrated successful implementation of a checklist protocol where no checklist was previously being used, with sustained use in an average of 67% of PPH cases over 20 months. Checklist use was consistent across subgroups and was associated with higher use of interventions shown to lower blood loss. KEY POINTS: · Our study showed sustainability of PPH checklist use over a 20-month period.. · PPH checklist use was associated with increased use of interventions known to reduce blood loss.. · Checklist was used consistently across patient subgroups; may help address inequities in obstetric outcomes..

Standardized Order Sets Do Not Eliminate Racial or Ethnic Inequities in Postpartum Pain Management.

Objective: To quantify the extent to which a standardized pain management order set reduced racial and ethnic inequities in post-cesarean pain evaluation and management. Methods: We conducted a retrospective cohort study to quantify racial and ethnic differences in pain evaluation and management before (July 2014-June 2016) and after implementation of a standardized post-cesarean order set (March 2017-February 2018). Electronic medical records were queried for pain scores >7/10, number of pain assessments, and opioid, nonsteroidal anti-inflammatory drug (NSAID), and acetaminophen doses. Outcomes were grouped into 0 to <24 and 24-48 h postpartum, and stratified by race/ethnicity (Hispanic, non-Hispanic Black [NHB], non-Hispanic White [NHW], Asian, and other), as documented in the electronic health record. Analyses included logistic regression for the categorical outcome of pain score >7 (severe pain), and linear regression, with propensity score adjustment. Main effect and interaction terms were used to calculate the difference-in-difference in pain process and outcome measures between the baseline and follow-up periods. Results: After order set implementation (N=888), severe pain remained more common among NHB patients (% pain scores >7 NHW vs. NHB 0 to <24 h: 22% vs. 33%, p=0.003; 24-48 h: 26% vs. 40%, p<0.001). Among all patients, pain management processes changed after implementation of the order set, with overall fewer assessments, less Opioids, and more nonopioid analgesics. However, racial and ethnic inequities in a number of assessments and in treatment were unchanged (all p for interaction >0.05), with the exception of a modest increase in NSAID doses 24-48 h postpartum for Hispanic patients. Conclusion: A standardized pain management order set reduced overall postpartum opioid use, but did not reduce racial and ethnic disparities in pain evaluation and management. Future work should investigate racial equity-focused education and interventions designed to eliminate disparities in pain management.

Electrocatalysis of the Oxygen Reduction Reaction by Copper Complexes with Tetradentate Tripodal Ligands.

The tetradentate tripodal ligand scaffold is capable of supporting the expected geometries of the copper ion during the oxygen reduction reaction (ORR) catalysis. As such, we probed the reactivity of copper complexes with these types of ligands by electronically and structurally tweaking the tris(pyridin 2-ylmethyl)amine (tmpa) scaffold by progressively replacing the terminal pyridines with carboxylate donors. This work shows that systems with one carboxylato donor (bpg = bis(pyridin-2-ylmethyl)glycine), (bpp = (3-(bis(pyridin-2-ylmethyl)amino)propanoic acid)) are active in electrocatalyzing the homogeneous ORR under circumneutral aqueous conditions. Turnover frequencies in the range from 105 to 106 s-1, on par with that for Cu-tmpa under identical conditions, were obtained. It is noteworthy that the CuII/CuI redox potentials for the Cu-bpg, Cu-bpp, and Cu-tmpa systems in phosphate-buffered water (pH 7, under Ar) are similar at -0.409, -0.375, and -0.401 V vs Ag/AgCl, respectively. This is rationalized by the influence of the Lewis acidity of the copper ions on the water coligand. Corroborating this are pKa values for [Cu(tmpa)(H2O)]2+, Cu(bpg)(H2O)]+, and [Cu(bpp)(H2O)]+ of 6.6, 8.8, and 10.2, respectively. Thus, the overall charge of the solution species for all three complexes will be +1 at pH 7 and this will be an important determinant for the redox potentials and, in turn, the catalytic overpotentials, which are also similar. A cis carboxylato donor offers H-bonding possibilities for exogenous resting state water and intermediate hydroperoxo coligands. This is reflected by the higher pKa values for Cu-bpp and Cu-bpg compared with that for Cu-tmpa, with the Cu-bpp system furnishing the least strained H-bonding.

Reducing Opioid Prescribing after Cesarean Delivery by Utilizing a Tailored Opioid Prescribing Algorithm.

OBJECTIVE: There are increasing efforts among health care systems to promote safe opioid prescribing; however, best practice for minimizing overprescription is not established. Our study aimed to evaluate the effect of a tailored opioid prescribing algorithm on opioid prescription quantities. STUDY DESIGN: A tailored opioid prescribing algorithm was developed to provide a recommended prescription quantity based on inpatient opioid use. A retrospective analysis of opioid prescribing 3 months before and after implementation was performed. Our primary outcome was the number of oxycodone 5-mg tablets prescribed. Subgroup analysis by oxycodone consumption in the 24 hour prior to discharge was performed. Patient satisfaction and unused opioid tablets were assessed by text message survey 2 weeks' postpartum. RESULTS: We included 627 (n = 313 preimplementation; n = 314 postimplementation) patients who underwent cesarean delivery. Clinical characteristics were similar between groups. The median number of oxycodone 5-mg tablets prescribed in the baseline group was 20 (interquartile range [IQR]: 20-30), compared with 5 (IQR: 0-10) in the tailored prescribing group (p < 0.0001). For patients with no opioid use in the 24 hours prior to discharge, the median number of tablets prescribed decreased from 20 (IQR: 10-20) to 0 (IQR: 0-5) following the intervention (p < 0.0001). The proportion of patients discharged without an opioid prescription increased from 7% (23/313) in the baseline group to 35% (111/314) in the tailored prescribing group (odds ratio: 6.9, 95% confidence interval [4.3, 11.1]). CONCLUSION: Tailored opioid prescribing reduced the number of opioid tablets prescribed and increased the proportion of patients who were discharged without an opioid prescription. KEY POINTS: · Opioid prescribing should be tailored by inpatient use.. · Tailored prescribing reduced opioid prescription amounts.. · Many patients do not require an opioid prescription..

Sulfonamido-Pincer Complexes of Cu(II) and the Electrocatalysis of O2 Reduction.

Heteroleptic copper complexes of an asymmetrical pincer ligand containing a central anionic sulfonamide donor (pyridine-2-yl-sulfonyl)(quinolin-8-yl)-amide (psq), which contains a central anionic sulfonamido donor have been prepared. Meridional κ3-N,N″,N‴ binding with the co-ligands acetate, chloride, or acetonitrile (MeCN), trans to the central sulfonamido N-donor, is revealed by the X-ray crystal structures of [Cu(OAc)(psq)(H2O)], [CuCl(psq)]2, and [Cu(psq)(MeCN)](PF6). Either overall distorted square pyramidal or octahedral geometries of the copper atom are satisfied by coordinated water in the case of the acetate complex or interactions with periphery sulfonamido oxygen atoms on adjacent molecules in the dimeric chloride and 1D polymeric acetonitrile complexes. The cyclic voltammogram (CV) of [Cu(OAc)(psq)(H2O)] shows a quasi-reversible CuII/CuI reduction at -0.930 V (vs Fc+/Fc0, MeCN), and an irreversible CuII/CuI reduction for [Cu(psq)(MeCN)](PF6) is seen at -0.838 V. This signal is split into two quasi-reversible redox processes on the addition of 2,2,2-trifluoroethanol (TFE). This suggests that TFE pushes a solution equilibrium toward a dimeric acetate complex analogous to [CuCl(psq)]2, which shows two quasi-reversible waves at -0.666 V and -0.904 V vs Fc+/Fc0 consistent with its dimeric solid-state structure. A comparison of the CVs of [Cu(OAc)(psq)(H2O)] under either a N2 or an O2 atmosphere revealed that this complex catalyzes turnover electro-reduction of O2 to H2O2 and H2O. The rate of reaction increases on addition of a weak organic acid, and a coulombic efficiency of 48% for H2O2 was determined by iodometric titration. We propose that a CuI complex formed on electroreduction binds O2 to yield an intermediate superoxide complex. On electron and proton transfer to this species, a bifurcated route back to the O2-activating CuI complex is feasible with either release of H2O2 or O-O cleavage resulting in the liberation of H2O. The CuI complex is regenerated by subsequent reduction and protonation to close the cycle.

A Click Chemistry-Based Artificial Metallo-Nuclease.

Artificial metallo-nucleases (AMNs) are promising DNA damaging drug candidates. Here, we demonstrate how the 1,2,3-triazole linker produced by the Cu-catalysed azide-alkyne cycloaddition (CuAAC) reaction can be directed to build Cu-binding AMN scaffolds. We selected biologically inert reaction partners tris(azidomethyl)mesitylene and ethynyl-thiophene to develop TC-Thio, a bioactive C3 -symmetric ligand in which three thiophene-triazole moieties are positioned around a central mesitylene core. The ligand was characterised by X-ray crystallography and forms multinuclear CuII and CuI complexes identified by mass spectrometry and rationalised by density functional theory (DFT). Upon Cu coordination, CuII -TC-Thio becomes a potent DNA binding and cleaving agent. Mechanistic studies reveal DNA recognition occurs exclusively at the minor groove with subsequent oxidative damage promoted through a superoxide- and peroxide-dependent pathway. Single molecule imaging of DNA isolated from peripheral blood mononuclear cells shows that the complex has comparable activity to the clinical drug temozolomide, causing DNA damage that is recognised by a combination of base excision repair (BER) enzymes.

Structure Activity Relationships for Reversible O2 Chemisorption by the Solid Phases of Co(salen) and Co(3F-salen).

The potential of solid-state materials comprising Co(salen) units for concentrating dioxygen from air was recognized over 80 years ago. While the chemisorptive mechanism at the molecular level is largely understood, the bulk crystalline phase plays important, yet unidentified roles. We have reverse crystal-engineered these materials and can for the first time describe the nanostructuring requisite for achieving reversible O2 chemisorption by Co(3R-salen) R = H or F, the simplest and most effective of the many known derivatives of Co(salen). Of the six phases of Co(salen) identified, α-ζ: α = ESACIO, ß = VEXLIU, γ, δ, ε, and ζ (this work), only γ, δ, ε, and ζ are capable of reversible O2 binding. Class I materials (phases γ, δ, and ε) are obtained by desorption (40-80 °C, atmospheric pressure) of the co-crystallized solvent from Co(salen)·(solv), solv = CHCl3, CH2Cl2, or 1.5 C6H6. The oxy forms comprise between 1:5 and 1:3 O2:[Co] stoichiometries. Class II materials achieve an apparent maximum of 1:2 O2:Co(salen) stoichiometries. The precursors for the Class II materials comprise [Co(3R-salen)(L)·(H2O)x], R = H, L = pyridine, and x = 0; R = F, L = H2O, and x = 0; R = F, L = pyridine, and x = 0; R = F, L = piperidine, and x = 1. Activation of these depends on the desorption of the apical ligand (L) that templates channels through the crystalline compounds with the Co(3R-salen) molecules interlocked in a Flemish bond brick pattern. The 3F-salen system produces F-lined channels proposed to facilitate O2 transport through the materials through repulsive interactions with the guest O2. We postulate that a moisture dependence of the activity of the Co(3F-salen) series is due to a highly specific binding pocket for locking in water via bifurcated hydrogen bonding to the two coordinated phenolato O atoms and the two ortho F atoms.

A comparison of the accuracy of mushroom identification applications using digital photographs.

OBJECTIVE: To compare the accuracy of three popular mushroom identification software applications in identifying mushrooms involved in exposures reported to the Victorian Poisons Information Centre and Royal Botanic Gardens Victoria. BACKGROUND: Over the past 10 years, an increasing number of software applications have been developed for use on smart phones and tablet devices to identify mushrooms. We have observed an increase in poisonings after incorrect identification of poisonous species as edible, using these applications. DESIGN: We compared the accuracy of three iPhone™ and Android™ mushroom identification applications: Picture Mushroom (Next Vision Limited©), Mushroom Identificator (Pierre Semedard©), and iNaturalist (iNaturalist, California Academy of Sciences©). Each app was tested independently by three researchers using digital photographs of 78 specimens sent to the Victorian Poisons Information Centre and Royal Botanic Gardens Victoria over a two-year period, 2020-2021. Mushroom identification was confirmed by an expert mycologist. For each app, individual and combined results were compared. RESULTS: Picture Mushroom was the most accurate of the three apps and correctly identified 49% (95% CI [0-100]) of specimens, compared with Mushroom Identificator (35% [15-56]) and iNaturalist (35% [0-76]). Picture Mushroom correctly identified 44% of poisonous mushrooms [0-95], compared with Mushroom Identificator (30% [1-58]) and iNaturalist (40% [0-84), but Mushroom Identificator identified more specimens of Amanita phalloides correctly (67%), compared to Picture Mushroom (60%) and iNaturalist (27%). Amanita phalloides was falsely identified, twice by Picture Mushroom and once by iNaturalist. CONCLUSIONS: Mushroom identification applications may be useful future tools to assist clinical toxicologists and the general public in the accurate identification of mushrooms species but, at present, are not reliable enough to exclude exposure to potentially poisonous mushrooms when used alone.

A Quality Improvement Effort to Reduce Inpatient Opioid Consumption following Cesarean Delivery.

OBJECTIVE: The amount of opioid prescribed following cesarean delivery (CD) is commonly in excess of patients' needs. An additional concern in a breastfeeding mother is neonatal opioid exposure. A maximum daily dose of 30 mg of oxycodone is recommended in breastfeeding women. Inadequate pain control can inhibit breastfeeding, as well as other negative consequences. We aimed to evaluate the effect of reducing the as-needed opioid ordered following CD on inpatient opioid consumption and analgesia. STUDY DESIGN: At our tertiary-care institution, our standard as-needed opioid order was reduced from oxycodone 5 to 10 mg every 4 hours to oxycodone 5 mg every 6 hours, in May 2019. Orders for scheduled acetaminophen and nonsteroidal anti-inflammatory drugs were unchanged. We compared opioid use and pain scores before (February 2019-April 2019) and after (May 2019-July 2019) the order modification. Our primary outcome was the proportion of patients using >30 mg of oxycodone in the 24 hours prior to hospital discharge. We further assessed 48-hour opioid consumption and patient-reported verbal pain scores. RESULTS: There were 559 patients who met inclusion criteria; 241 preintervention patients and 318 postintervention patients. In the preintervention group, 14.5% (35/241) used >30-mg oxycodone in the 24 hours before discharge, compared with 5.0% (16/318) after the order set change (relative risk [RR] = 0.34, 95% confidence interval [CI]: 0.19, 0.61; number needed to treat [NNT] = 10.5). There was no change in the proportion of women with one or more pain score >7 (preintervention: 44.4% [107/241], postintervention: 43.1% [137/318], p = 0.756) or >4 and ≤7 (preintervention: 36.9% [89/241], postintervention: 36.9% [125/318], p = 0.567), nor was there a change in mean pain score (mean ± standard deviation [SD]: preintervention = 2.8 ± 1.6 and postintervention = 2.7 ± 1.4, p = 0.464). CONCLUSION: Reducing the amount of opioid ordered after CD reduced the proportion of post-CD patients exceeding the maximum recommended daily oxycodone dose for breastfeeding women. KEY POINTS: · Inpatient opioid prescribing influences usage.. · Opioid orders influence consumption.. · Reducing opioids may not increase pain..

An experimental laboratory reactor for quantitative kinetic studies of disinfection byproduct formation using membrane inlet mass spectrometry.

RATIONALE: The type and quantity of environmentally problematic disinfection byproducts (DBPs) produced during chlorination of water depend on the natural organic matter and organic contaminants that raw water contains, and on the operational conditions of the drinking water treatment process. There is a need for a fast and quantitative method that determines which DBPs are produced and monitors the chemical dynamics during a drinking water treatment. METHODS: A small experimental chemical reactor (50 mL) was mounted directly onto the membrane inlet interface of a membrane inlet mass spectrometer (MIMS). In this setup, the membrane was the only separation between the reaction mixture in the chemical reactor and the open ion source of the mass spectrometer 2 cm away. Water samples to be chlorinated were placed in the reactor and the chlorination reaction was initiated by injection of hypochlorite. The formation of intermediates and products was monitored using either full-scan mass spectra or selected ion monitoring of relevant ions. RESULTS: An algorithm for analyte quantification was successfully developed for analysis of the complex mixtures of phenol (a model for waterborne organic compounds), chlorinated intermediates and trihalomethane products which simultaneously pass the membrane into the mass spectrometer. The algorithm is based upon the combined use of standard addition and an internal standard, and all analytes could be quantified at nanomolar concentrations corresponding to realistic water treatment conditions. Experiments carried out in the temperature range 15-60°C showed that the reaction dynamics change with operational parameters, for example in tap versus deionized water. CONCLUSIONS: We have successfully shown that an experimental laboratory reactor directly interfaced with a MIMS can be used for quantitative monitoring of the chemical dynamics during a water treatment. This technique could provide rapid assistance in the optimization of operating parameters for minimizing DBP production.

Probing Noncovalent Interactions in [3,3]Metaparacyclophanes.

Arene-arene interactions are fundamentally important in molecular recognition. To precisely probe arene-arene interactions in cyclophanes, we designed and synthesized (2,6-phenol)paracyclophanes and (2,6-aniline)paracyclophanes that possess two aromatic rings in close proximity. Fine-tuning the aromatic character of one aromatic ring by fluorine substituents enables investigations on the intramolecular interactions between the electron-rich phenol and aniline with tetra-H- and tetra-F-substituted benzene. pKa measurements revealed that the tetra-F-template increases the acidity of the phenol (ΔpKa = 0.55). X-ray crystallography and computational analyses demonstrated that all [3,3]metaparacyclophanes adopt cofacial parallel conformations, implying the presence of π-π stacking interactions. Advanced quantum chemical analyses furthermore revealed that both electrostatic interactions and orbital interactions provide the key contribution to the structure and stability of [3,3]metaparacyclophanes.

Facile transmetallation of [SbIII(DOTA)]- renders it unsuitable for medical applications.

The antimony(iii) complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (DOTA) has been prepared and its exceptionally low stability observed. The Sb(iii) ion in Na[Sb(DOTA)]·4H2O shows an approximately square antiprismatic coordination geometry that is close to superimposable to the Bi(iii) geometry in [Bi(DOTA)]- in two phases containing this anion, Na[Bi(DOTA)]·4H2O, [H3O][Bi(DOTA)]·H2O for which structures are also described. Interestingly, DOTA itself in [(H6DOTA)]Cl2·4H2O·DMSO shows the same orientation of the N4O4 metal binding cavity reflecting the limited flexibility of DOTA in an octadentate coordination mode. In 8-coordinate complexes it can however accommodate M(iii) ions with r ion spanning a relatively wide range from 87 pm (Sc(iii)) to 117 pm (Bi(iii)). The larger Bi3+ ion appears to be the best metal-ligand size match since [Bi(DOTA)]- is associated with greater complex stability. In the solution state, [Sb(DOTA)]- is extremely susceptible to transmetallation by trivalent ions (Sc(iii), Y(iii), Bi(iii)) and, significantly, even by biologically important divalent metal ions (Mg(ii), Ca(ii), Zn(ii)). In all cases just one equivalent is enough to displace most of the Sb(iii). [Sb(DOTA)]- is resistant to hydrolysis; however, since biologically more abundant metal ions easily substitute the antimony, DOTA complexes will not be suitable for deployment for the delivery of the, so far unexploited, theranostic isotope pair 119Sb and 117Sb.

Probing the Lewis Acidity of Boronic Acids through Interactions with Arene Substituents.

Boronic acids are Lewis acids that exist in equilibrium with boronate forms in aqueous solution. Here we experimentally and computationally investigated the Lewis acidity of 2,6-diarylphenylboronic acids; specially designed phenylboronic acids that possess two flanking aromatic rings with tunable aromatic character. Hammett analysis of 2,6-diarylphenylboronic acids reveals that their Lewis acidity remains unchanged upon the introduction of EWG/EDG at the distant para position of the flanking aromatic rings. Structural and computational studies demonstrate that polar-π interactions and solvation effects contribute to the stabilization of boronic acids and boronate forms by aromatic rings. Our physical-organic chemistry work highlights that boronic acids and boronates can be stabilized by aromatic systems, leading to an important molecular knowledge for rational design and development of boronic acid-based catalysts and inhibitors of biomedically important proteins.

Cooperative Co-Activation of Water and Hypochlorite by a Non-Heme Diiron(III) Complex.

Aqueous solutions of the iron(III) complex of N,N,N'-tris(2-pyridylmethyl)ethylenediamine-N'-acetate (tpena) react with hypochlorite (ClO-) to produce the reactive high-valent [FeIV(O)(tpena)]+. Under catalytic conditions, in bicarbonate-buffered media (pH 8) with a set ionic strength (10 mM NaCl), kinetic analysis shows that two equivalents of [FeIV(O)(tpena)]+ per one ClO- are produced, with benign chloride ions the only byproduct. An unprecedented supramolecular activation of ClO- by {(HCO3)⊂[(tpena)FeIII(µ-O)FeIII(Htpena)]}2+ is proposed. This mode of activation has great advantage for use in the catalytic oxidation of C-H bonds in water since: (i) the catalyst scaffold is protected from oxidative degradation and (ii) undesirable radical side reactions which produce toxic chlorinated compounds are circumvented by this novel coactivation of water and ClO-. The unique activation mechanism by the Fe-tpena system makes possible the destruction of organic contaminants as an add-on technology to water disinfection by chlorination, demonstrated here through (i) the catalytic oxidation of micropollutant metaldehyde, and (ii) mineralization of the model substrate formate. The resting-state speciation at pH 3, 5, 7, and 9, as well as the catalytically active iron speciation are characterized with Mössbauer and EPR spectroscopy and supported by DFT calculations. Our study provides fundamentally new insights into the design and activation mode of iron-based catalysts relevant to applications in water remediation.

Preparation of organocobalt(iii) complexes via O2 activation.

The coupling of selective C-H activation with O2 activation is an important goal for organic synthesis. New experimental and computational results, along with the results from experimental work accumulated over many decades, now unequivocally link O2 activation with C-H activation by the classic Co(salen) complexes. A common holistic mechanistic framework can rationalise the formation of ostensibly diverse peroxo, superoxo, organo and alkoxide complexes of CoIII(salen). DFT calculations show that cobalt(iii)superoxo, dicobalt(iii)peroxo and cobalt(iii)hydroperoxo complexes are all viable intermediates as participants in hydrogen atom transfer reactions, whereas a Co(iv)oxo intermediate is unlikely. The reaction conditions will determine the pathway followed and all pathways are initiated through the initial formation of a superoxo complex, CoIII(salen)(O2˙)(MeOH) (EPR: g = 2.025, A = 19 G). Organo and alkoxide ligands are derived from solvent media and the trends in reactivity reveal that combination of the pKa and BDE of the C-H of the respective solvent substrates are important. These data explain why landmark, structurally characterized, µ2-η1,η2-peroxide and η1-superoxide Co(salen)-O2 adducts were predominantly isolated from solvents with high C-H pKa values (DMSO, DMF, DMA).

Engineering the Oxidative Potency of Non-Heme Iron(IV) Oxo Complexes in Water for C-H Oxidation by a cis Donor and Variation of the Second Coordination Sphere.

A series of iron(IV) oxo complexes, which differ in the donor (CH2py or CH2COO-) cis to the oxo group, three with hemilabile pendant donor/second coordination sphere base/acid arms (pyH/py or ROH), have been prepared in water at pH 2 and 7. The νFe═O values of 832 ± 2 cm-1 indicate similar FeIV═O bond strengths; however, different reactivities toward C-H substrates in water are observed. HAT occurs at rates that differ by 1 order of magnitude with nonclassical KIEs (kH/kD = 30-66) consistent with hydrogen atom tunneling. Higher KIEs correlate with faster reaction rates as well as a greater thermodynamic stability of the iron(III) resting states. A doubling in rate from pH 7 to pH 2 for substrate C-H oxidation by the most potent complex, that with a cis-carboxylate donor, [FeIVO(Htpena)]2+, is observed. Supramolecular assistance by the first and second coordination spheres in activating the substrate is proposed. The lifetime of this complex in the absence of a C-H substrate is the shortest (at pH 2, 3 h vs up to 1.3 days for the most stable complex), implying that slow water oxidation is a competing background reaction. The iron(IV)═O complex bearing an alcohol moiety in the second coordination sphere displays significantly shorter lifetimes due to a competing selective intramolecular oxidation of the ligand.

Do Sulfonamides Interact with Aromatic Rings?

Aromatic rings form energetically favorable interactions with many polar groups in chemical and biological systems. Recent molecular studies have shown that sulfonamides can chelate metal ions and form hydrogen bonds, however, it is presently not established whether the polar sulfonamide functionality also interacts with aromatic rings. Here, synthetic, spectroscopic, structural, and quantum chemical analyses on 2,6-diarylbenzenesulfonamides are reported, in which two flanking aromatic rings are positioned close to the central sulfonamide moiety. Fine-tuning the aromatic character by substituents on the flanking rings leads to linear trends in acidity and proton affinity of sulfonamides. This physical-organic chemistry study demonstrates that aromatic rings have a capacity to stabilize sulfonamides via through-space NH-π interactions. These results have implications in rational drug design targeting electron-rich aromatic rings in proteins.

Photosynthesis of a Dihydroimidazopyridine Chelate Shines Light on the Reactions of a Photoactivated Iron(III) Complex with O2.

The high-spin (S = 5/2) meridional diastereoisomer of [FeIII(tpena)]2+ (tpena = N,N,N'-tris(2-pyridylmethyl)ethylendiamine-N'-acetate), mer-[Fe(tpena)]2+, undergoes photolytic CO2 release to produce an iron(II) intermediate of a radical dihydroimidazopyridine ligand (L•). The structure of this unprecedented transient iron(II)(L•) complex is supported by UV-vis and Mössbauer spectroscopies, DFT calculations, as well as the X-ray structural characterization of an µ-oxo iron(III) complex of the oxidized derivative of L•, namely, [FeIII2O(Cl)2(L+)2](ClO4)4(MeCN)2 (L+ = 2-(2-(bis(pyridin-2-ylmethyl)amino)ethyl)-2,3-dihydro-1H-imidazo[1,5-a]pyridin-4-ium). [FeIII2O(Cl)2(L+)2]4+ is obtained only in the absence of O2. Under aerobic conditions, O2 will intercept the iron(II)(L•) complex to form a putative Fe(III)-alkylperoxide complex which cascades to an iron(II) complex of SBPy3 (SBPy3 = N,N-bis(2-pyridylmethyl)amine-N-ethyl-2-pyridine-2-aldimine). Thus, through different oxidative pathways, the unknown ligand L+ or SBPy3 forms by loss of a one-carbon-atom or a two-carbon-atom unit, respectively, from the glycyl arm of tpena. Acceleration of the photodecarboxylation step is achieved by addition of thiocyanate because of transient formation of a more photoreactive NCS- adduct of [Fe(tpena)]2+. This has allowed for kinetic observation of the reaction of [FeII(L•)]2+ with O2 which is, unexpectedly, promoted also by light. We propose that this corresponds to the energy needed for the conversion of the ring-closed radical ligand L• to a ring-opened tautomer to allow for O2 insertion between the C and Fe atoms of the iron(II) complex.

Probing Halogen-π versus CH-π Interactions in Molecular Balance.

Molecular balances based on the dibenzobicyclo[3.2.2]nonane template enable probing of the competition between halogen-π and CH-π interactions. Structural, NMR spectroscopic, and computational analyses revealed that the π system can favorably interact both with C-X or C-H functionalities, depending on the size of the functional group.

Through-Space Polar-π Interactions in 2,6-Diarylthiophenols.

The front cover artwork is provided by Marijn Maas from the group of Prof. Jasmin Mecinovic (University of Southern Denmark). The image shows the stabilization of thiols by aromatic rings, as a result of energetically favorable SH-π interactions in a designed small molecule and in proteins. Read the full text of the Article at 10.1002/cphc.202000132.