Expanding the Scope of Aluminum Chemistry with Noninnocent Ligands.

ConspectusAluminum is the most abundant metal in the earth's crust at 8%, and it is also widely available domestically in many countries worldwide, which ensures a stable supply chain. To further the applications of aluminum (Al), such as in catalysis and electronic and energy storage materials, there has been significant interest in the synthesis and characterization of new Al coordination compounds that can support electron transfer (ET) and proton transfer (PT) chemistry. This has been achieved using redox and chemically noninnocent ligands (NILs) combined with the highly stable M(III) oxidation state of Al and in some cases the heavier group 13 ions, Ga and In.When ligands participate in redox chemistry or facilitate the breaking or making of new bonds, they are often termed redox or chemically noninnocent, respectively. Al(III) in particular supports rich ligand-based redox chemistry because it is so redox inert and will support the ligand across many charge and protonation states without entering into the reaction chemistry. To a lesser extent, we have reported on the heavier group 13 elements Ga and In, and this chemistry will also be included in this Account, where available.This Account is arranged into two technical sections, which are (1) Structures of Al-NIL complexes and (2) Reactivity of Al-NIL complexes. Highlights of the research work include reversible redox chemistry that has been enabled by ligand design to shut down radical coupling pathways and to prevent loss of H2 from unsaturated ligand sites. These reversible redox properties have in turn enabled the characterization of Class III electron delocalization through Al when two NIL are bound to the Al(III) in different charge states. Characterization of the metalloaromatic character of square planar Al and Ga complexes has been achieved, and characterization of the delocalized electronic structures has provided a model within which to understand and predict the ET and PT chemistry of the NIL group 13 compounds. The capacity of Al-NIL complexes to perform ET and PT has been employed in reactions that use ET or PT reactivity only or in reactions where coupled ET/PT affords hydride transfer chemistry. As an example, ligand-based PT reactions initiate metal-ligand cooperative bond activation pathways for catalysis: this includes acceptorless dehydrogenation of formic acid and anilines and transfer hydrogenation chemistry. In a complementary approach, ligand based ET/PT chemistry has been used in the study of dihydropyridinate (DHP-) chemistry where it was shown that N-coordination of group 13 ions lowers kinetic barriers to DHP- formation. Taken together, the discussion presented herein illustrates that the NIL chemistry of Al(III), and also of Ga(III) and In(III) holds promise for further developments in catalysis and energy storage.

Ligand Conjugation Directs the Formation of a 1,3-Dihydropyridinate Regioisomer.

The selective formation of the 1,4-dihydropyridine isomer of NAD(P)H is mirrored by the selective formation of 1,4-dihydropyridinate ligand-metal complexes in synthetic systems. Here we demonstrate that ligand conjugation can be used to promote selective 1,3-dihydropyridinate formation. This represents an advance toward controlling and tuning the selectivity in dihydropyridinate formation chemistry. The reaction of (I2P2-)Al(THF)Cl [1; I2P = bis(imino)pyridine; THF = tetrahydrofuran] with the one-electron oxidant (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) afforded (I2P-)Al(TEMPO)Cl (2), which can be reduced with sodium to the twice-reduced ligand complex (I2P2-)Al(TEMPO) (3). Compounds 2 and 3 serve as precursors for high-yielding and selective routes to an aluminum-supported 1,3-dihydropyridinate complex via the reaction of 2 with 3 equiv of potassium metal or the reaction of 3 with KH.

Metallated dihydropyridinates: prospects in hydride transfer and (electro)catalysis.

Hydride transfer (HT) is a fundamental step in a wide range of reaction pathways, including those mediated by dihydropyridinates (DHP-s). Coordination of ions directly to the pyridine ring or functional groups stemming therefrom, provides a powerful approach for influencing the electronic structure and in turn HT chemistry. Much of the work in this area is inspired by the chemistry of bioinorganic systems including NADH. Coordination of metal ions to pyridines lowers the electron density in the pyridine ring and lowers the reduction potential: lower-energy reactions and enhanced selectivity are two outcomes from these modifications. Herein, we discuss approaches for the preparation of DHP-metal complexes and selected examples of their reactivity. We suggest further areas in which these metallated DHP-s could be developed and applied in synthesis and catalysis.

Group 13 ion coordination to pyridyl breaks the reduction potential vs. hydricity scaling relationship for dihydropyridinates.

The relationship Epvs. ΔGH- correlates the applied potential (Ep) needed to drive organohydride formation with the strength of the hydride donor that is formed: in the absence of kinetic effects Epvs. ΔGH- should be linear but it would be more energy efficient if Ep could be shifted anodically using kinetic effects. Biological hydride transfers (HT) performed by cofactors including NADH and lactate racemase do occur at low potentials and functional modeling of those processes could lead to low energy HT reactions in electrosynthesis and to accurate models for cofactor chemistry. Herein we probe the influence of N-alkylation or N-metallation on ΔGH- for dihydropyridinates (DHP-) and on Ep of the DHP- precursors. We synthesized a series of DHP- complexes of the form (pz2HP-)E via hydride transfer from their respective [(pz2P)E]+ forms where E = AlCl2+, GaCl2+ or Me+. Relative ΔGH- for the (pz2HP-)E series all fall within 1 kcal mol-1, and ΔGH- for (pz2HP)CH3 was approximated as 47.5 ± 2.5 kcal mol-1 in MeCN solution. Plots of Epvs. ΔGH- including [(pz2P)E]+ suggest kinetic effects shift Ep anodically by ∼215 mV.

Changes in parental sleep from pregnancy to postpartum: A meta-analytic review of actigraphy studies.

Sleep changes in new parents are widely observed but there is no extant meta-analysis of changes to sleep parameters in this group. We completed a meta-analysis of changes in actigraphy-measured parent sleep between pregnancy and the end of the first year of a child's life. A search of six databases was completed. Following review using predetermined inclusion and exclusion criteria, 16 papers were left for review. Data were extracted, analysed and each paper was reviewed for methodological quality. Where possible, subgroup analysis was completed based on time since birth and location of the study, and meta-regression of parent age. Parents' total sleep time and sleep efficiency were shown to decrease following the birth of a child, with wake after sleep onset increasing. This change was most notably observed in the first four weeks after birth. Up to 16 weeks post-birth, differences were still apparent, but sleep parameters were beginning to return to pre-birth levels. New parents experience a significant change in multiple sleep parameters following the birth of a child. Future data collection, using best practice actigraphy measurement, reporting a broader range of variables and including fathers, as well as mothers, is warranted.

Group 13 ion coordination to pyridyl models NAD+ reduction potentials.

N-alkylation and N-metallation of pyridine are explored herein to understand how metal-ligand complexes can model NAD+ redox chemistry. Syntheses of substituted dipyrazolylpyridine (pz2P) compounds (pz2P)Me+ (1+) and (pz2P)GaCl2+ (2+) are reported, and compared with (pz2P)AlCl2(THF)+ and transition element pz2P complexes from previous reports. Cyclic voltammetry measurements of cationic 1+ and 2+ show irreversible reduction events ∼900 mV anodic those for neutral pz2P complexes of divalent metals. We proposed that N-metallation using Group 13 ions of 3+ charge provides an electrochemical model for N-alkylated pyridyls like NAD+.

A "resistance calculator": Simple stewardship intervention for refining empiric practices of antimicrobials in acute-care hospitals.

OBJECTIVE: In the era of widespread resistance, there are 2 time points at which most empiric prescription errors occur among hospitalized adults: (1) upon admission (UA) when treating patients at risk of multidrug-resistant organisms (MDROs) and (2) during hospitalization, when treating patients at risk of extensively drug-resistant organisms (XDROs). These errors adversely influence patient outcomes and the hospital's ecology. DESIGN AND SETTING: Retrospective cohort study, Shamir Medical Center, Israel, 2016. PATIENTS: Adult patients (aged >18 years) hospitalized with sepsis. METHODS: Logistic regressions were used to develop predictive models for (1) MDRO UA and (2) nosocomial XDRO. Their performances on the derivation data sets, and on 7 other validation data sets, were assessed using the area under the receiver operating characteristic curve (ROC AUC). RESULTS: In total, 4,114 patients were included: 2,472 patients with sepsis UA and 1,642 with nosocomial sepsis. The MDRO UA score included 10 parameters, and with a cutoff of ≥22 points, it had an ROC AUC of 0.85. The nosocomial XDRO score included 7 parameters, and with a cutoff of ≥36 points, it had an ROC AUC of 0.87. The range of ROC AUCs for the validation data sets was 0.7-0.88 for the MDRO UA score and was 0.66-0.75 for nosocomial XDRO score. We created a free web calculator (https://assafharofe.azurewebsites.net). CONCLUSIONS: A simple electronic calculator could aid with empiric prescription during an encounter with a septic patient. Future implementation studies are needed to evaluate its utility in improving patient outcomes and in reducing overall resistances.