Tripodal P₃^XFe–N₂ Complexes (X = B, Al, Ga): Effect of the Apical Atom on Bonding, Electronic Structure, and Catalytic N₂-to-NH₃ Conversion

Terminal dinitrogen complexes of iron ligated by tripodal, tetradentate P₃^X ligands (X = B, C, Si) have previously been shown to mediate catalytic N₂-to-NH₃ conversion (N₂RR) with external proton and electron sources. From this set of compounds, the tris(phosphino)borane (P₃^B) system is most active under all conditions canvassed thus far. To further probe the effects of the apical Lewis acidic atom on structure, bonding, and N₂RR activity, Fe–N₂ complexes supported by analogous group 13 tris(phosphino)alane (P₃^(Al)) and tris(phosphino)gallane (P₃^(Ga)) ligands are synthesized. The series of P₃^XFe–N₂^([0/1−]) compounds (X = B, Al, Ga) possess similar electronic structures, degrees of N₂ activation, and geometric flexibility as determined from spectroscopic, structural, electrochemical, and computational (DFT) studies. However, treatment of [Na(12-crown-4)₂][P₃^XFe–N₂] (X = Al, Ga) with excess acid/reductant in the form of HBAr^F₄/KC₈ generates only 2.5 ± 0.1 and 2.7 ± 0.2 equiv of NH₃ per Fe, respectively. Similarly, the use of [H₂NPh₂][OTf]/Cp^*₂Co leads to the production of 4.1 ± 0.9 (X = Al) and 3.6 ± 0.3 (X = Ga) equiv of NH₃. Preliminary reactivity studies confirming P₃^XFe framework stability under pseudocatalytic conditions suggest that a greater selectivity for hydrogen evolution versus N₂RR may be responsible for the attenuated yields of NH₃ observed for P₃^(Al)Fe and P₃^(Ga)Fe relative to P₃^BFe

Transition Metal Complexes for Challenging Reductive Transformations: From Nitrogen Fixation Catalysts to Photoreductants

Transition metal complexes are routinely employed as catalysts for the reductive cleavage of a diverse array of strong chemical bonds. Two notable research areas that exemplify such utility are nitrogen fixation, involving cleavage of the notoriously unreactive triple bond of dinitrogen (N₂) to form ammonia (NH₃), and photoredox catalysis, wherein powerful photoreductants generated by visible light excitation facilitate challenging reduction steps in a host of synthetic organic transformations. This thesis focuses on a number of structure-function studies conducted on group 8 transition metal complexes that catalyze N₂-to-NH₃ conversion, commonly referred to as the nitrogen reduction reaction (N₂RR), and on homoleptic tungsten(0) arylisocyanides that, among their many attractive qualities, possess highly reducing electronically excited states. These comparative studies provide fundamental insight into critical design features which can guide efforts to improve existing N₂RR or photocatalysts or rationally tailor them for specific applications. Chapter 2 details the effect apical Lewis acidic atom substitution in P₃XFe platforms (X = B, Al, Ga) has on structure, bonding, and N₂RR activity. Structural, spectroscopic, electrochemical, and computational studies reveal that all three P₃XFe systems possess similar electronic structures, degrees of N₂ activation, and geometric flexibility, but P₃AlFe and P₃GaFe display significantly lower N₂RR efficiencies than P₃BFe when treated with HBArF₄/KC₈ or [H₂NPh₂][OTf]/Cp*₂Co at –78 °C in Et₂O. Chapter 3 reports on isostructural tris(phosphino)silyl Ru and Os complexes that mediate catalytic N₂RR. The study of the homologous, isostructural series of complexes P₃SiM (M = Fe, Ru, Os) helps delineate important factors for N₂RR catalyst design. Low-temperature protonation of P₃SiOs–N₂⁻ yields P₃SiOs=NNH₂⁺, representing the first instance of an Os–N₂ species being converted to a protonated Os–NxHy product. Chapter 4 communicates a novel series of homoleptic tungsten(0) photoactive complexes supported by fused-ring (CN-1-(2-iPr)-Naph) or alkynyl-bridged (CNDippCCAr) arylisocyanide ligands. Systematic studies establish facile electronic variation of the CNDippCCAr platform as a straightforward method by which to rationally modulate the ground- and excited-state properties of W(CNDippCCAr)₆ complexes. The photophysical properties of W(CN-1-(2-iPr)-Naph)₆ reveal potential benefits of utilizing fused-ring arylisocyanide ligands in the design of this class of photosensitizers.</p

Catalytic Nitrogen-to-Ammonia Conversion by Osmium and Ruthenium Complexes

Despite the critical role Ru and Os complexes have played in the development of transition metal dinitrogen chemistry, they have not been shown to mediate catalytic N_2-to-NH_3 conversion (N_2RR), nor have M-N_xH_y complexes been derived from protonation of their M-N_2 precursors. To help delineate factors for N_2RR catalysis, we report on isostructural tris(phosphino)silyl Ru and Os complexes that mediate catalytic N_2RR, and compare their activities with an isostructural Fe complex. The Os system is most active, and liberates more than 120 equiv NH_3 per Os center in a single batch experiment using Cp*_2Co and [H_2NPh_2][OTf] as reductant and acid source. Isostructural Ru and Fe complexes generate little NH_3 under the same conditions. Protonation of Os-N_2– affords a structurally characterized Os=NNH_2+ hydrazido species that mediates NH_3 generation, suggesting it is a plausible intermediate of the catalysis. Inactive Os hydrides are characterized that form during catalysis

Catalytic Nitrogen-to-Ammonia Conversion by Osmium and Ruthenium Complexes

Despite the critical role Ru and Os complexes have played in the development of transition metal dinitrogen chemistry, they have not been shown to mediate catalytic N_2-to-NH_3 conversion (N_2RR), nor have M-N_xH_y complexes been derived from protonation of their M-N_2 precursors. To help delineate factors for N_2RR catalysis, we report on isostructural tris(phosphino)silyl Ru and Os complexes that mediate catalytic N_2RR, and compare their activities with an isostructural Fe complex. The Os system is most active, and liberates more than 120 equiv NH_3 per Os center in a single batch experiment using Cp*_2Co and [H_2NPh_2][OTf] as reductant and acid source. Isostructural Ru and Fe complexes generate little NH_3 under the same conditions. Protonation of Os-N_2– affords a structurally characterized Os=NNH_2+ hydrazido species that mediates NH_3 generation, suggesting it is a plausible intermediate of the catalysis. Inactive Os hydrides are characterized that form during catalysis

Third-Generation W(CNAr)₆ Photoreductants (CNAr = Fused-Ring and Alkynyl-Bridged Arylisocyanides)

Homoleptic tungsten(0) arylisocyanides possess photophysical and photochemical properties that rival those of archetypal ruthenium(II) and iridium(III) polypyridine complexes. Previous studies established that extending the π-system of 2,6-diisopropylphenylisocyanide (CNDipp) by coupling aryl substituents para to the isocyanide functionality results in W(CNDippAr)₆ oligoarylisocyanide complexes with greatly enhanced metal-to-ligand charge transfer (MLCT) excited-state properties relative to those of W(CNDipp)₆. Extending electronic modifications to delineate additional design principles for this class of photosensitizers, herein we report a series of W(CNAr)₆ compounds with naphthalene-based fused-ring (CN-1-(2-ⁱPr)-Naph) and CNDipp-based alkynyl-bridged (CNDipp^(CC)Ar) arylisocyanide ligands. Systematic variation of the secondary aromatic system in the CNDippCCAr platform provides a straightforward method to modulate the photophysical properties of W(CNDipp^(CC)Ar)₆ complexes, allowing access to an extended range of absorption/luminescence profiles and highly reducing excited states, while maintaining the high molar absorptivity MLCT absorption bands, high photoluminescence quantum yields, and long excited-state lifetimes of previous W(CNAr)₆ complexes. Notably, W(CN-1-(2-iPr)-Naph)₆ exhibits the longest excited-state lifetime of all W(CNAr)₆ complexes explored thus far, highlighting the potential benefits of utilizing fused-ring arylisocyanide ligands in the construction of tungsten(0) photoreductants

Third-Generation W(CNAr)₆ Photoreductants (CNAr = Fused-Ring and Alkynyl-Bridged Arylisocyanides)

Homoleptic tungsten(0) arylisocyanides possess photophysical and photochemical properties that rival those of archetypal ruthenium(II) and iridium(III) polypyridine complexes. Previous studies established that extending the π-system of 2,6-diisopropylphenylisocyanide (CNDipp) by coupling aryl substituents para to the isocyanide functionality results in W(CNDippAr)₆ oligoarylisocyanide complexes with greatly enhanced metal-to-ligand charge transfer (MLCT) excited-state properties relative to those of W(CNDipp)₆. Extending electronic modifications to delineate additional design principles for this class of photosensitizers, herein we report a series of W(CNAr)₆ compounds with naphthalene-based fused-ring (CN-1-(2-ⁱPr)-Naph) and CNDipp-based alkynyl-bridged (CNDipp^(CC)Ar) arylisocyanide ligands. Systematic variation of the secondary aromatic system in the CNDippCCAr platform provides a straightforward method to modulate the photophysical properties of W(CNDipp^(CC)Ar)₆ complexes, allowing access to an extended range of absorption/luminescence profiles and highly reducing excited states, while maintaining the high molar absorptivity MLCT absorption bands, high photoluminescence quantum yields, and long excited-state lifetimes of previous W(CNAr)₆ complexes. Notably, W(CN-1-(2-iPr)-Naph)₆ exhibits the longest excited-state lifetime of all W(CNAr)₆ complexes explored thus far, highlighting the potential benefits of utilizing fused-ring arylisocyanide ligands in the construction of tungsten(0) photoreductants

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Cyano-Ambivalence: Spectroscopy and Photophysics of [Ru(diimine)(CN-BR₃)₄]²⁻ Complexes

The UV-visible absorption and luminescence spectra of [Ru(diimine)(CN)₄]²⁻ derivatives have been tuned over wide ranges through variations in solvent, substituents on the diimine ligand, and boronation of the cyanide ligands. Trifluoromethyl substitution at the 4 and 4′ positions of the diimine induces red shifts in metal-to-ligand charge-transfer (MLCT) absorption and luminescence bands. Boronation of the cyanide ligands produces substantial blue shifts in MLCT energies. The combination of diimine trifluoromethylation and cyanide boronation produces MLCT blue shifts that are about 75% as large as those produced by boronation alone

Cyano-Ambivalence: Spectroscopy and Photophysics of [Ru(diimine)(CN-BR₃)₄]²⁻ Complexes

The UV-visible absorption and luminescence spectra of [Ru(diimine)(CN)₄]²⁻ derivatives have been tuned over wide ranges through variations in solvent, substituents on the diimine ligand, and boronation of the cyanide ligands. Trifluoromethyl substitution at the 4 and 4′ positions of the diimine induces red shifts in metal-to-ligand charge-transfer (MLCT) absorption and luminescence bands. Boronation of the cyanide ligands produces substantial blue shifts in MLCT energies. The combination of diimine trifluoromethylation and cyanide boronation produces MLCT blue shifts that are about 75% as large as those produced by boronation alone

Axillary local anesthetic spread after the thoracic interfacial ultrasound block – a cadaveric and radiological evaluation

Background: Oral opioid analgesics have been used for management of peri- and postoperative analgesia in patients undergoing axillary dissection. The axillary region is a difficult zone to block and does not have a specific regional anesthesia technique published that offers its adequate blockade. Methods: After institutional review board approval, anatomic and radiological studies were conducted to determine the deposition and spread of methylene blue and local anesthetic injected respectively into the axilla via the thoracic inter-fascial plane. Magnetic Resonance Imaging studies were then conducted in 15 of 34 patients scheduled for unilateral breast surgery that entailed any of the following: axillary clearance, sentinel node biopsy, axillary node biopsy, or supernumerary breasts, to ascertain the deposition and time course of spread of solution within the thoracic interfascial plane in vivo. Results: Radiological and cadaveric studies showed that the injection of local anesthetic and methylene blue via the thoracic inter-fascial plane, using ultrasound guide technique, results in reliable deposition into the axilla. In patients, the injection of the local anesthetic produced a reliable axillary sensory block. This finding was supported by Magnetic Resonance Imaging studies that showed hyper-intense signals in the axillary region. Conclusions: These findings define the anatomic characteristics of the thoracic interfascial plane nerve block in the axillary region, and underline the clinical potential of this novel nerve block. Resumo: Justificativa: Os analgésicos orais à base de opioides têm sido usados para o manejo da analgesia nos períodos peri e pós-operatório de pacientes submetidos à linfadenectomia axilar. A região axilar é uma zona difícil de bloquear e não há registro de uma técnica de anestesia regional específica que ofereça o seu bloqueio adequado. Métodos: Após a aprovação do Conselho de Ética institucional, estudos anatômicos e radiológicos foram realizados para determinar a deposição e disseminação de azul de metileno e anestésico local, respectivamente injetados na axila via plano interfascial torácico. Exames de ressonância magnética foram então realizados em 15 de 34 pacientes programados para cirurgia de mama unilateral envolvendo qualquer um dos seguintes procedimentos: esvaziamento axilar, biópsia de linfonodo sentinela, biópsia de linfonodo axilar, ou mamas supranumerárias, para verificar a deposição e tempo de propagação da solução dentro do plano interfascial torácico in vivo. Resultados: Estudos radiológicos e em cadáveres mostraram que a injeção de anestésico local e azul de metileno via plano interfascial torácico usando a técnica guiada por ultrassom resulta em deposição confiável na axila. Nos pacientes, a injeção de anestésico local produziu um bloqueio sensitivo axilar confiável. Esse achado foi corroborado por estudos de ressonância magnética que mostraram sinais hiperintensos na região axilar. Conclusões: Esses achados definem as características anatômicas do bloqueio da região axilar e destacam o potencial clínico desses novos bloqueios. Keywords: Anesthesia, conduction, Axilla, Intercostal muscles, Brachial plexus block, Intercostal nerves, Lymph node excision, Ultrasonography, Palavras-chave: Anestesia por condução, Axila, Músculos intercostais, Bloqueio do plexo braquial, Nervos intercostais, Excisão de linfonodo, Ultrassonografi