Field- and Temperature-Dependent Paramagnetic Relaxation Enhancements in Co(II) Trispyrazolylmethanes.

A comprehensive field- and temperature-dependent examination of nuclear magnetic resonance paramagnetic relaxation enhancements (PREs) for the constitutive protons of [Co(Tpm)2][BF4]2 is presented. Data for an apically substituted derivative clearly establish that bis-Tpm complexes of Co(II) undergo Jahn-Teller dynamics about the molecular threefold axis. PREs from the parent Tpm complex were used to numerically extract the electron relaxation times (T1e). The Tpm complex showed field-dependent behavior, with an approximately 40% higher activation barrier than the related trispyrazolylborate (Tp) complex, based on fits to the T1e vs T, B0 data. Analysis of the field-dependent line widths revealed a surprisingly large contribution from susceptibility (Curie) relaxation (20-35% at the highest field), and a molecular radius (9.5 Å) that is consistent with a tightly associated counterion slowing rotation in solution. Density functional theory showed a shared vibration that is consistent with the Jahn-Teller and appears proportionately higher in energy in [Co(Tpm)2]2+. Complete active-space self-consistent field calculations support ascribing electron relaxation to enhanced mixing of the two Eg orbital sets that accompanies the tetragonal distortion and the differences in electron correlation times to the higher Jahn-Teller activation barrier in [Co(Tpm)2]2+.

Manipulating Excited State Properties of Iridium Phenylpyridine Complexes with "Push-Pull" Substituents.

We have prepared a series of complexes of the type [IrIII(ppy)2(L]n+ complexes (1-4), where ppy is a substituted 2-phenylpyridine and L is a chelating phosphine thioether ligand. The parent complex (1) comprises an unsubstituted phenylpyridine ligand, whereas complex 2 contains a nitro substituent on the pyridine ring, complex 3 features a diphenylamine group on the phenyl ring, and 4 has both nitro and diphenylamine groups. Crystallographic, 1H NMR, and elemental analysis data are consistent with each of the chemical formulae. DFT (density functional theory) computational results show a complicated electronic structure with contributions from Ir, ppy, and the PS ligand. Ultrafast pump-probe data show strong contributions from the phenylpyridine moieties as well as strong panchromatic excited state absorption transitions. The data show that nitro and/or diphenylamine substituents dominate the spectroscopy of this series of compounds.

Controlling Photoisomerization Reactivity Through Single Functional Group Substitutions in Ruthenium Phosphine Sulfoxide Complexes.

We report the crystallography, emission spectra, femtosecond pump-probe spectroscopy, and density functional theory computations for a series of ruthenium complexes that comprise a new class of chelating triphenylphosphine based ligands with an appended sulfoxide moiety. These ligands differ only in the presence of the para-substitutent (e.g., H, OCH3, CF3). The results show a dramatic range in photoisomerization reactivity that is ascribed to differences in the electron density of the phosphine ligand donated to the ruthenium and the nature of the excited state.

Zwitterionic Design Principle of Nickel(II) Catalysts for Carbonylative Polymerization of Cyclic Ethers.

Zwitterionic structure is necessary for NiII complexes to catalyze carbonylative polymerization (COP) of cyclic ethers. The cationic charge at the NiII center imparts sufficient electrophilicity to the Ni-acyl bond for it to react with cyclic ethers to give an acyl-cyclic ether oxonium intermediate, while the ligand-centered anionic charge ensures that the resultant oxonium cation is ion-paired with the Ni0 nucleophile. The current catalysts give non-alternating copolymers of carbon monoxide and cyclic ethers and are the most effective when both ethylene oxide and tetrahydrofuran are present as the cyclic ether monomers.

Structure and electronics in dimeric boron π expanded azine and salphen complexes.

Although boron-based fluorophores incorporating nitrogenous chelating ligands have received much attention, there has been little work on examples of boron-salphen and azine derivatives. In this report, we present several π expanded boron salphen type complexes, incorporating both bis(2-hydroxynaphthaldehyde)azine as well as ortho, meta and para variants of the analogous 2-hydroxynaphthaldehyde salphen compounds. For the azine, we observed only the formation of a single BF2 adduct, while for the naphth-phen compounds dimeric BF2 binding was observed. All new compounds were fully characterized via X-ray diffraction, and both DFT and TDDFT studies were carried out to probe the electronic structures of these fluorophores.

Paramagnetic Resonance of Cobalt(II) Trispyrazolylmethanes and Counterion Association.

Paramagnetic resonance studies (EPR, ESEEM, ENDOR, and NMR) of a series of cobalt(II) bis-trispyrazolylmethane tetrafluoroborates are presented. The complexes studied include the parent, unsubstituted ligand (Tpm), two pyrazole-substituted derivatives (4Me and 3,5-diMe), and tris(1-pyrazolyl)ethane (Tpe), which includes a methyl group on the apical carbon atom. NMR and ENDOR establish the magnitude of 1H hyperfine couplings, while ESEEM provides information on the coordinated 14N. The data show that the pyrazole 3-position is more electron rich in the Tpm analogues, that the geometry about the apical atom influences the magnetic resonance, and that apical atom geometry appears more fixed in Tpm than in Tp. NMR and ENDOR establish that the BF4- counterion remains associated in fluid solution. In the case of the Tpm3,5Me complex, it appears to associate in solution, in the same position it occupies in the X-ray structure.

Re(CO)3-Templated Formation of Aza(dibenzo)dipyrromethenes.

The Re(CO)3 unit was used to template the formation of aza(dibenzopyrro)methene (ADBM) in the presence of pyridine or N-methylimidazole. The products of these template reactions are six-coordinate complexes, with a facial arrangement of the carbonyls, a bidentate ADBM, and a sixth ligand (pyridine or N-methylimiadozle). Three types of ADBM ligands are produced from these reactions, depending on the degree of hydrolysis; bis(imine)-terminated, bis(oxo)-terminated, and mixed-imine/oxo chelates were formed.

Using Hydrazine to Link Ferrocene with Re(CO)3: A Modular Approach.

Acetyl ferrocene and diacetyl ferrocene both readily react with an excess of hydrazine to afford the corresponding hydrazone compounds. These compounds can then be linked to Re(CO)3 via a metal-mediated Schiff base reaction, resulting in a series of ferrocene-Re(CO)3 conjugates with different stoichiometries. Conjugates with 1:1, 1:2, and 2:1 ferrocene: Re(CO)3 ratios can be produced via this "modular" type synthesis approach. Several examples of these conjugates were structurally characterized, and their spectroscopic, electrochemical, and spectroelectrochemical behaviors were investigated. The electronic structures of these compounds were also probed using DFT and TDDFT calculations.

Sudden unexpected death in early childhood: general observations in a series of 151 cases: Part 1 of the investigations of the San Diego SUDC Research Project.

PURPOSE: The purpose of this study was to determine the major subcategories and clinicopathologic features of sudden unexpected death in young children in a large retrospective cohort, and to confirm the association of sudden unexplained death in children (abbreviated by us for unexplained deaths as SUDC) with hippocampal pathology and/or febrile seizures. METHODS: We undertook analysis of a retrospective cohort of 151 cases, of which 80% (121/151) were subclassified as SUDC, 11% (16/151) as explained, 7% (10/151) as undetermined, and 3% (4/151) as seizure-related. RESULTS: There were no significant differences between SUDC and explained cases in postnatal, gestational, or postconceptional age, frequency of preterm birth, gender, race, or organ weights. In contrast, 96.7% (117/121) of the SUDC group were discovered during a sleep period compared to 53.3% (8/15) of the explained group (p < 0.001), and 48.8% (59/121) of the SUDC cases had a personal and/or family history of febrile seizures compared to 6.7% (1/15) of the explained group (p < 0.001). Of the explained deaths, 56% (9/16) were subclassified as infection, 31% (5/16) cardiac, 6% (1/16) accidental, and 6% (1/16) metabolic. Two of the three cases specifically tested for cardiac channelopathies at autopsy based upon clinical indications had genetic variants in cardiac genes, one of uncertain significance. Bacterial cultures at autopsy typically revealed organisms interpreted as contaminants. Two of the four seizure-related deaths were witnessed, with two of the brains from these cases showing generalized malformations. Hippocampal anomalies, including a specific combination we termed hippocampal maldevelopment associated with sudden death, were found in almost 50% (40/83) of the SUDC and undetermined cases in which hippocampal sections were available. CONCLUSIONS: This study highlights the key role for the hippocampus, febrile seizures, and sleep in SUDC pathophysiology. It also demonstrates the role of known predisposing conditions such as cardiac channelopathies and infections in causing sudden unexpected death in childhood, and the need for improved ancillary testing and protective strategies in these cases, even when the cause of death is established at autopsy.

Hippocampal malformation associated with sudden death in early childhood: a neuropathologic study: Part 2 of the investigations of The San Diego SUDC Research Project.

PURPOSE: Sudden unexplained death in childhood (SUDC), while rare, accounts for an important fraction of unexpected deaths in children >1 year of age. Previously we reported an association between febrile seizures, hippocampal maldevelopment, and sudden, unexpected deaths in young children (1-6 years), termed "hippocampal maldevelopment associated with sudden death (HMASD)." Here, we characterize in greater detail the hippocampal pathology in a large cohort of cases (n = 42) of this entity, and attempt to define possible new entities responsible for sudden, unexplained death in young children without HMASD/febrile seizure phenotypes. METHODS: We performed comparative analysis on cases, which we classified in a cohort of 89 sudden and unexpected deaths as HMASD, explained deaths, SUDC with febrile seizure phenotype (SUDC-FS) but without hippocampal pathology, and SUDC (without hippocampal pathology or febrile seizure phenotype). RESULTS: The frequency of each subgroup was: HMASD 48% (40/83); SUDC 27% (22/83); SUDC-FS 18% (15/83); explained 7% (6/83). HMASD was characterized clinically by sudden, sleep-related death, term birth, and discovery in the prone position. Key morphologic features of HMASD were focal granule cell bilamination of the dentate gyrus with or without asymmetry and/or malrotation of the hippocampus, associated with significantly increased frequencies of 11 other developmental abnormalities. We identified no other distinct phenotype in the unexplained categories, except for an association of febrile seizures without hippocampal maldevelopment. CONCLUSIONS: HMASD is a distinct clinicopathologic entity characterized by a likely developmental failure of neuronal migration in the dentate gyrus. Future research is needed to determine the causal role of HMASD in sudden death in early childhood.

Sudden unexplained death in childhood: A comparison of cases with and without a febrile seizure history.

OBJECTIVE: We considered whether a subset of children with sudden unexplained death in childhood (SUDC) and a history of febrile seizures (FS) may parallel those in sudden unexpected death in epilepsy (SUDEP). The prevalence of a history of FS was examined, and factors that may distinguish SUDC cases with and without FS were described. METHODS: Characteristics were assessed in 123 consecutive children with SUDC reported to the SUDC program (4/1/11-3/31/14) by their parents. Parental interview covered the decedent's medical history, circumstances of death, environmental factors, cause of death, and family medical history. Features of SUDC cases were compared by FS history. RESULTS: Overall, 31.7% of SUDC cases had a history of FS, among which 74.4% had simple FS. Compared to those without a history of FS, a history of FS was associated with a greater median age at death (p = 0.03) and death during the weekdays (p = 0.02). Terminal fever was similar in those with and without FS. The median time from FS to death was 6.0 months (interquartile range [IQR] 3.0-10.0). In all SUDC cases, prone position at death, death during sleep, and unwitnessed deaths predominated. SIGNIFICANCE: There are parallels among SUDC, sudden infant deaths, and sudden unexpected death in epilepsy (SUDEP) with regard to prone position, unwitnessed deaths mostly during sleep, and male predominance. In children with SUDC and a history of FS, terminal fever may increase the risk for an unwitnessed terminal seizure. The greater than expected prevalence of a FS history and the proportion with terminal fever or illness in this cohort suggests that some SUDC deaths may be seizure related and therefore have potential commonalities with SUDEP.

Combined MCD/DFT/TDDFT Study of the Electronic Structure of Axially Pyridine Coordinated Metallocorroles.

A series of metallocorroles were investigated by UV-vis and magnetic circular dichroism spectroscopies. The diamagnetic distorted square-pyramidal main-group corrole Ga(tpfc)py (2), the diamagnetic distorted octahedral transition-metal adduct Co(tpfc)(py)2 (3), and paramagnetic distorted octahedral transition-metal complex Fe(tpfc)(py)2 (4) [H3tpfc = tris(perfluorophenyl)corrole] were studied to investigate similarities and differences in the electronic structure and spectroscopy of the closed- and open-shell metallocorroles. Similar to the free-base H3tpfc (1), inspection of the MCD Faraday B-terms for all of the macrocycles presented in this report revealed that a ΔHOMO < ΔLUMO [ΔHOMO is the energy difference between two highest energy corrole-centered π-orbitals and ΔLUMO is the energy difference between two lowest energy corrole-centered π*-orbitals originating from ML ± 4 and ML ± 5 pairs of perimeter] condition is present for each complex, which results in an unusual sign-reversed sequence for π-π* transitions in their MCD spectra. In addition, the MCD spectra of the cobalt and the iron complexes were also complicated by a number of charge-transfer states in the visible region. Iron complex 4 also exhibits a low-energy absorption in the NIR region (1023 nm). DFT and TDDFT calculations were used to elaborate the electronic structures and provide band assignments in UV-vis and MCD spectra of the metallocorroles. DFT and TDDFT calculations predict that the orientation of the axial pyridine ligand(s) has a very minor influence on the calculated electronic structures and absorption spectra in the target systems.

Enhanced helical folding of ortho-phenylenes through the control of aromatic stacking interactions.

The ortho-phenylenes are a simple class of foldamers, with the formation of helices driven by offset aromatic stacking interactions parallel to the helical axis. For the majority of reported o-phenylene oligomers, the perfectly folded conformer comprises perhaps 50-75% of the total population. Given the hundreds or thousands of possible conformers for even short oligomers, this distribution represents a substantial bias toward the folded state. However, "next-generation" o-phenylenes with better folding properties are needed if these structures are to be exploited as functional units within more complex architectures. Here, we report several new series of o-phenylene oligomers, varying both the nature and orientation of the substituents on every repeat unit. The conformational behavior was probed using a combination of NMR spectroscopy, DFT calculations, and X-ray crystallography. We find that increasing the electron-withdrawing character of the substituents gives oligomers with substantially improved folding properties. With moderately electron-withdrawing groups (acetoxy), we observe >90% of the perfectly folded conformer, and stronger electron withdrawing groups (triflate, cyano) give oligomers for which misfolded states are undetectable by NMR. The folding of these oligomers is only weakly solvent-dependent. General guidelines for the assessment of o-phenylene folding by NMR and UV-vis spectroscopy are also discussed.

Hippocampal asymmetry and sudden unexpected death in infancy: a case report.

The differential diagnosis of known entities associated with sudden unexpected death in infancy is ever expanding. Here we report the case of a 10-month-old infant boy whose clinical presentation mimicked that of the sudden infant death syndrome (SIDS). This presentation included the typical features of SIDS: sleep-related death; prone position upon discovery; and minor illness within 2 days of death. Nevertheless, neuropathologic examination revealed striking hippocampal asymmetry and microdysgenesis similar to that reported previously by us in toddlers with sleep-related sudden death. Hippocampal maldevelopment in the setting of sudden death in infants and toddlers is analogous to sudden unexpected death in epilepsy associated with temporal lobe pathology, and suggests a possible role for seizures in the terminal events leading to sudden death. This report serves to alert pediatric and forensic pathologists to hippocampal asymmetry and microdysgenesis in the differential diagnosis of sudden infant death mimicking SIDS.

The synthesis and structures of 1,1'-bis(sulfonyl)ferrocene derivatives.

A series of 1,1'-bis(sulfonyl)ferrocene compounds were produced via the 1,1'-bis(sulfonate)ferrocene ammonium salt. This compound can be readily converted to 1,1' bis(sulfonylchloride)ferrocene. By varying stoichiometry and reaction times, both mono- and bis-sulfonamide derivatives can be synthesized. All new compounds presented in this report have been structurally characterized. The structures of the bis-sulfonamide systems are similar to the well-studied bis(amide) ferrocene compounds. Intermolecular hydrogen bonding is observed, typically between NH and SO groups of neighboring sulfonamides. However in the bis(GABA) derivative, intermolecular NH to CO hydrogen bonding interactions are present.

Sudden death, febrile seizures, and hippocampal and temporal lobe maldevelopment in toddlers: a new entity.

Recently, we reported hippocampal and temporal lobe abnormalities in 5 toddlers with sudden unexplained death in childhood (SUDC). The association of these anomalies with a high incidence (40%) of individual/family histories of simple febrile seizures in the cases raised concern that febrile seizures can be associated with death. In a series of 64 toddlers with sudden death, we tested the hypothesis that an SUDC subset is characterized by hippocampal and temporal lobe maldevelopment and an individual and/or family history of simple familial seizures. Cases of sudden and unexplained death in children aged 1.0 to 5.9 years (median 1.7 years) were divided into groups based upon a history of febrile or nonfebrile seizures, familial febrile seizures, and autopsy classification of cause of death. Forty-nine of the 64 cases (77%) were classified as SUDC, of which 40% had an individual/family history of febrile seizures. Of the 26 SUDC cases with available hippocampal sections, 62% (16/26) had hippocampal and temporal lobe anomalies, including 82% (9/11) of cases with an individual/family history of febrile seizures. Cases with these anomalies were all found dead during a sleep period, typically in the prone (87%) position. We conclude that a potential new entity may account for the majority of SUDC in toddlers, defined by sleep-related death in the prone position, individual/family history of febrile seizures, and hippocampal and temporal lobe anomalies. The mechanism of death appears analogous to sudden death in (temporal lobe) epilepsy, with a putative unwitnessed seizure during sleep leading to airway occlusion and death. This study mandates further research into the potential link between simple febrile seizures and death.

Sudden death in toddlers associated with developmental abnormalities of the hippocampus: a report of five cases.

Sudden unexplained death in childhood (SUDC) is the sudden death of a child older than 1 year of age that remains unexplained after review of the clinical history, circumstances of death, and autopsy with appropriate ancillary testing. We report here 5 cases of SUDC in toddlers that we believe define a new entity associated with hippocampal anomalies at autopsy. All of the toddlers died unexpectedly during the night, apparently during sleep. Within 48 hours before death, 2 toddlers had fever, 3 had a minor upper respiratory tract infection, and 3 experienced minor head trauma. There was a history of febrile seizures in 2 (40%) and a family history of febrile seizures in 2 (40%). Hippocampal findings included external asymmetry and 2 or more microdysgenetic features. The incidence of certain microdysgenetic features was substantially increased in the temporal lobes of these 5 cases compared with the temporal lobes of 39 (control) toddlers with the causes of death established at autopsy (P < 0.01). We propose that these 5 cases define a potential subset of SUDC whose sudden death is caused by an unwitnessed seizure arising during sleep in the anomalous hippocampus and producing cardiopulmonary arrest. Precipitating factors may be fever, infection, and/or minor head trauma. Suggested risk factors are a history of febrile seizures and/or a family history of febrile seizures. Future studies are needed to confirm these initial findings and to define the putative links between sudden death, hippocampal anomalies, and febrile seizures in toddlers.