Cannabis Legalization and Resource Use for Ingestions by Young Children.

OBJECTIVE: In conjunction with widening legalization, there has been a rapid rise in unintentional cannabis ingestions in young children. We sought to determine if the legal status of recreational cannabis was associated with resource use in young children with cannabis poisoning. METHODS: This retrospective cross-sectional study of the Pediatric Health Information System included emergency department encounters between January 2016 and April 2023 for children <6 years of age with a diagnosis indicating cannabis ingestion. The primary exposure was recreational cannabis legalization status in the state in which the encounter occurred. We used logistic regression models to determine the association of recreational cannabis legality with resource utilization outcomes, adjusting for demographic covariates. RESULTS: We included 3649 children from 47 hospitals; 29% of encounters occurred in places in which recreational cannabis was legal. Compared with environments in which recreational cannabis was illegal, cannabis-legal locations had lower uses of advanced neuroimaging (24% vs 35%; adjusted odds ratio [aOR], 0.65; 95% confidence interval [CI]: 0.55-0.77), lumbar puncture (1.6% vs 3.8%; aOR, 0.42; 95% CI: 0.24-0.70), ICU admission (7.9% vs 11%; aOR, 0.71; 95% CI: 0.54-0.93), and mechanical ventilation (0.8% vs 2.9%; aOR, 0.30; 95% CI: 0.14-0.58). Urine testing was more common in places in which recreational cannabis was legal (71% vs 58%; aOR, 1.87; 95% CI: 1.59-2.20). CONCLUSIONS: State-level legalization of recreational cannabis was associated with a significant decrease in the utilization of advanced medical resources in cases of cannabis intoxication in children. These findings suggest the need for a focus on policies and procedures to minimize invasive testing in cases of cannabis intoxication in children.

Do young children with known cannabis intoxication benefit from further neurological-based testing or imaging?

BACKGROUND: Recent work has demonstrated that children with unintentional cannabis ingestions often undergo extensive ancillary testing such as head imaging or lumbar puncture. To better understand the yield of these tests, our objective was to describe the frequency of additional significant diagnoses in children with cannabis ingestion. METHODS: We performed a retrospective cross-sectional study of the Pediatric Health Information System (PHIS) database, including ED encounters from January 2016 to April 2023 with a diagnosis indicating cannabis exposure in children <6 years of age. We assessed the frequency of co-diagnoses that would be found on head imaging, lumbar puncture, or toxicology testing. RESULTS: We included 4132 ED encounters for cannabis ingestion from 47 hospitals. Of these, 1243 (30%) received head imaging and 130 (3.1%) underwent lumbar puncture. There were 23 children (0.6%) with diagnosis of skull fracture or intracranial hemorrhage, 4 (<0.1%) with intracranial neoplasm, and 0 (0%) with a diagnosis for meningitis or intracranial abscess. Presence of discharge diagnosis for other drugs was also uncommon. The most frequent drug ingestion co-diagnoses were cocaine in 43 (1.0%) and opioids in 22 (0.5%) encounters. CONCLUSION: In children with cannabis intoxication, high rates of head imaging and lumbar puncture are likely driven by the signs of altered mental status at presentation. These data suggest that if cannabis ingestion is considered early and identified quickly with testing, neuroimaging, particularly that with ionizing radiation, may be low yield.

Asthmalitis? Diagnostic Variability of Asthma and Bronchiolitis in Children <24 Months.

BACKGROUND AND OBJECTIVES: Bronchiolitis and asthma have similar acute clinical presentations in young children yet have opposing treatment recommendations. We aimed to assess the role of age and other factors in the diagnosis of bronchiolitis and asthma in children <24 months of age. METHODS: We conducted a retrospective cross-sectional analysis of the Pediatric Health Information System database. We included children aged <2 years diagnosed with bronchiolitis, asthma, wheeze, or bronchospasm in emergency department or hospital encounters from 2017 to 2021. We described variation by age and between institutions. We used mixed-effects models to assess factors associated with a non-bronchiolitis diagnosis in children 12 to 23 months of age. RESULTS: We included 554 158 encounters from 42 hospitals. Bronchiolitis made up 98% of encounters for children <3 months of age, whereas asthma diagnoses increased with age and were included in 44% of encounters at 23 months of age. Diagnosis patterns varied widely between hospitals. In children 12 to 23 months of age, the odds of a non-bronchiolitis diagnosis increased with month of age (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.12-1.13), male sex (OR 1.37, 95% CI 1.35-1.40), non-Hispanic Black race (OR 1.54, 95% CI 1.50-1.58), number of previous encounters (OR 2.73, 95% CI 2.61-2.86, for 3 or more encounters), and previous albuterol use (OR 2.24, 95% CI 2.16-2.32). CONCLUSIONS: Non-bronchiolitis diagnoses and the use of inhaled bronchodilators and systemic steroids for acute wheezing respiratory illness increase with month of age in children aged 0 to 23 months. Better definitions of clinical phenotypes of bronchiolitis and asthma would allow for more appropriate treatment in acute care settings, particularly in children 12 to 23 months of age.

Risk of Bacteremia in Febrile Children and Young Adults With Sickle Cell Disease in a Multicenter Emergency Department Cohort.

Importance: Bacteremia is a major cause of morbidity and mortality in children and young adults with sickle cell disease (SCD), but among those presenting to the emergency department (ED) with fever, the absolute risk of, risk factors associated with, and outcomes of bacteremia are poorly defined. Objective: To obtain contemporary data on the absolute risk of, risk factors associated with, and outcomes associated with bacteremia in children and young adults with SCD presenting to the ED with fever. Design, Setting, and Participants: A multicenter retrospective cohort study was conducted of individuals with SCD younger than 22 years (young adults) presenting to EDs within the Pediatric Health Information Systems database from January 1, 2016, to December 31, 2021, with fever (identified by diagnostic codes for fever or the collection of blood samples for cultures and intravenous antibiotic administration). Data analysis was performed from May 17 to December 15, 2022. Main Outcomes and Measures: The risk of bacteremia (defined by diagnostic coding) was identified in these children and young adults, and univariate analyses and multivariable regression were used to examine patient-level factors and bacteremia. Results: A total of 35 548 encounters representing 11 181 individual patients from 36 hospitals were evaluated. The median age of the cohort was 6.17 (IQR, 2.36-12.11) years and 52.9% were male. Bacteremia was present in 405 encounters (1.1%, 95% CI, 1.05%-1.26%). A history of bacteremia, osteomyelitis, stroke, central line-associated bloodstream infection (CLABSI), central venous catheter, or apheresis was associated with the diagnosis of bacteremia, while age, sex, hemoglobin SC genotype, and race and ethnicity were not. In the multivariable analysis, individuals with a history of bacteremia (odds ratio [OR], 1.36; 95% CI, 1.01-1.83), CLABSI (OR, 6.39; 95% CI, 3.02-13.52), and apheresis (OR, 1.77; 95% CI, 1.22-2.55) had higher odds of bacteremia. Conclusions and Relevance: The findings of this large cohort study suggest that bacteremia in children and young adults with SCD presenting with fever is rare. A history of invasive bacterial infection, CLABSI, or a central line appears to be associated with bacteremia, while age and SCD genotype are not.

Variation in Emergency Department Use of Racemic Epinephrine and Associated Outcomes for Croup.

OBJECTIVES: Racemic epinephrine (RE) is commonly administered for croup in the emergency department (ED). Our objectives were to examine variation in RE use between EDs, to determine whether ED variation in RE use is associated with hospital or patient factors, and to evaluate the associations between the rates of hospital-specific ED RE use and patient outcomes. METHODS: We performed a retrospective cohort study using the Pediatric Heath Information System of children aged 3 months to 10 years with croup in the ED. We used mixed-effects regression to calculate risk-standardized proportions of patients receiving RE in each ED and to analyze the relationship between risk-standardized institutional RE use and individual patient odds of hospital admission, ICU admission, and ED revisits. RESULTS: We analyzed 231 683 patient visits from 39 hospitals. ED administration of RE varied from 14% to 48% of visits (median, 24.5%; interquartile range, 20.0%-27.8%). A total of 8.6% of patients were hospitalized and 1% were admitted to the ICU. After standardizing for case mix and site effects, increasing ED use of RE per site was associated with increasing patient odds of hospital admission (odds ratio [OR], 1.39-95%; confidence interval [CI], 1.01-1.91), but not ICU admission (OR, 1.39; 95% CI, 0.99-1.97) or ED revisit (OR, 1.00; 95% CI, 0.92-1.09). CONCLUSIONS: In this large, observational study, RE administration varied widely across EDs. Increased RE use by site was associated with increased odds of hospital admission for individual patients when controlling for patient factors. These results suggest further standardization of RE use in children with croup is warranted.

Diurnal Variation in Frequency and Severity of Croup in the Emergency Department.

BACKGROUND: Emergency department (ED) presentation for croup is thought to occur more often at night, but evidence for its diurnal variation is sparse. Our objectives were to describe the diurnal patterns of ED presentation in children with croup and to determine whether time of arrival associated with severe clinical outcomes. METHODS: We conducted a retrospective cohort study using the Pediatric Health Information System. We included children 3 months to 11 years of age with an ED encounter for croup from 2016 through 2020. We quantified ED encounters by arrival hour and used generalized linear mixed-effects models to determine association between arrival time and racemic epinephrine use, hospitalization, intensive care unit (ICU) admission, and revisits. RESULTS: There was considerable diurnal variation in ED visits for croup. A total of 126 186 children (60.1%) presented to the ED at night (between 8 pm and 8 am), and 83 763 children presented during the day (39.9%). Peak arrival time was 12:00 am (14 189 encounters) and the nadir was at 2:00 pm (5231 encounters). Children presenting during overnight hours had increased odds of the use of racemic epinephrine (odds ratio [OR] 1.33; 95% confidence interval [95% CI], 1.30-1.36), but reduced odds of hospitalization (OR 0.76; 95% CI, 0.73-0.78), ICU admission (OR 0.61; 95% CI, 0.58-0.68), and 3 day ED revisits (OR 0.86; 95% CI, 0.83-0.90). CONCLUSIONS: Children with croup present to the ED more commonly at night. Children presenting to the ED with croup at night have greater odds of being treated with racemic epinephrine, but reduced odds of hospitalization, ICU admission, and return visits.

Assessment of Temporal Patterns and Patient Factors Associated With Oseltamivir Administration in Children Hospitalized With Influenza, 2007-2020.

Importance: Oseltamivir therapy is recommended for all pediatric inpatients with influenza, particularly those with high-risk conditions, although data regarding its uptake and benefits are limited. Objective: To describe temporal patterns and independent patient factors associated with the use of oseltamivir and explore patterns in resource use and patient outcomes among children hospitalized with influenza. Design, Setting, and Participants: This multicenter retrospective cross-sectional study was conducted at 36 tertiary pediatric hospitals participating in the Pediatric Health Information System in the US. A total of 70 473 children younger than 18 years who were hospitalized with influenza between October 1, 2007, and March 31, 2020, were included. Exposures: Hospitalization with a diagnosis of influenza. Main Outcomes and Measures: The primary outcome was the use of oseltamivir, which was described by influenza season and by hospital. Patient factors associated with oseltamivir use were assessed using multivariable mixed-effects logistic regression models. Secondary outcomes were resource use (including antibiotic medications, chest radiography, supplemental oxygen, positive pressure ventilation, central venous catheter, and intensive care unit [ICU]) and patient outcomes (length of stay, late ICU transfer, 7-day hospital readmission, use of extracorporeal membrane oxygenation, and in-hospital mortality), which were described as percentages per influenza season. Results: Among 70 473 children hospitalized with influenza, the median (IQR) age was 3.65 (1.05-8.26) years; 30 750 patients (43.6%) were female, and 39 715 (56.4%) were male. Overall, 16 559 patients (23.5%) were Black, 36 184 (51.3%) were White, 14 133 (20.1%) were of other races (including 694 American Indian or Alaska Native [1.0%], 2216 Asian [3.0%], 372 Native Hawaiian or Pacific Islander [0.5%], and 10 850 other races [15.4%]), and 3597 (5.1%) were of unknown race. A total of 47 071 patients (66.8%) received oseltamivir, increasing from a low of 20.2% in the 2007-2008 influenza season to a high of 77.9% in the 2017-2018 season. Use by hospital ranged from 43.2% to 79.7% over the entire study period and from 56.5% to 90.1% in final influenza season studied (2019-2020). Factors associated with increased oseltamivir use included the presence of a complex chronic condition (odds ratio [OR], 1.42; 95% CI, 1.36-1.47), a history of asthma (OR, 1.31; 95% CI, 1.23-1.38), and early severe illness (OR, 1.19; 95% CI, 1.13-1.25). Children younger than 2 years (OR, 0.81; 95% CI, 0.77-0.85) and children aged 2 to 5 years (OR, 0.83; 95% CI, 0.79-0.88) had lower odds of receiving oseltamivir. From the beginning (2007-2008) to the end (2019-2020) of the study period, the use of antibiotic medications (from 74.4% to 60.1%) and chest radiography (from 59.2% to 51.7%) decreased, whereas the use of oxygen (from 33.6% to 29.3%), positive pressure ventilation (from 10.8% to 7.9%), and central venous catheters (from 2.5% to 1.0%) did not meaningfully change. Patient outcomes, including length of stay (median [IQR], 3 [2-5] days for all seasons), readmissions within 7 days (from 4.0% to 3.4%), use of extracorporeal membrane oxygenation (from 0.5% to 0.5%), and in-hospital mortality (from 1.1% to 0.8%), were stable from the beginning to the end of the study period. Conclusions and Relevance: In this cross-sectional study of children hospitalized with influenza, the use of oseltamivir increased over time, particularly among patients with high-risk conditions, but with wide institutional variation. Patient outcomes remained largely unchanged. Further work is needed to evaluate the impact of oseltamivir therapy in this population.

Association of Early Oseltamivir With Improved Outcomes in Hospitalized Children With Influenza, 2007-2020.

Importance: Oseltamivir is recommended for all children hospitalized with influenza, despite limited evidence supporting its use in the inpatient setting. Objective: To determine whether early oseltamivir use is associated with improved outcomes in children hospitalized with influenza. Design, Setting, and Participants: This multicenter retrospective study included 55 799 children younger than 18 years who were hospitalized with influenza from October 1, 2007, to March 31, 2020, in 36 tertiary care pediatric hospitals who participate in the Pediatric Health Information System database. Data were analyzed from January 2021 to March 2022. Exposures: Early oseltamivir treatment, defined as use of oseltamivir on hospital day 0 or 1. Main Outcomes and Measures: The primary outcome was hospital length of stay (LOS) in calendar days. Secondary outcomes included 7-day hospital readmission, late (hospital day 2 or later) intensive care unit (ICU) transfer, and a composite outcome of in-hospital death or use of extracorporeal membrane oxygenation (ECMO). Inverse probability treatment weighting (IPTW) based on propensity scoring was used to address confounding by indication. Mixed-effects models were used to compare outcomes between children who did and did not receive early oseltamivir treatment. Outcomes were also compared within high-risk subgroups based on age, presence of a complex chronic condition, early critical illness, and history of asthma. Results: The analysis included 55 799 encounters from 36 hospitals. The median (IQR) age of the cohort was 3.61 years (1.03-8.27); 56% were male, and 44% were female. A total of 33 207 patients (59.5%) received early oseltamivir. In propensity score-weighted models, we found that children treated with early oseltamivir had shorter LOS (median 3 vs 4 days; IPTW model ratio, 0.52; 95% CI, 0.52-0.53) and lower odds of all-cause 7-day hospital readmission (3.5% vs 4.8%; adjusted odds ratio [aOR], 0.72; 95% CI, 0.66-0.77), late ICU transfer (2.4% vs 5.5%; aOR, 0.41; 95% CI, 0.37-0.46), and the composite outcome of death or ECMO use (0.9% vs 1.4%; aOR, 0.63; 95% CI, 0.54-0.73). Conclusions and Relevance: Early use of oseltamivir in hospitalized children was associated with shorter hospital stay and lower odds of 7-day readmission, ICU transfer, ECMO use, and death. These findings support the current recommendations for oseltamivir use in children hospitalized with influenza.

Transient synovitis of the hip: Current practice and risk of misdiagnosis.

INTRODUCTION: Transient synovitis (TS) is a common and benign cause of hip pain in children, but must be distinguished from more serious entities such as septic arthritis, osteomyelitis, and pyomyositis. Our objectives were to determine the risk of missed bacterial musculoskeletal infection and rates of diagnostic testing in children diagnosed with TS. METHODS: We performed a cohort study using the Pediatric Heath Information System of children 1-10 years diagnosed with TS in the ED. We determined rates of missed bacterial musculoskeletal infection (defined as a new diagnosis of septic arthritis, osteomyelitis, or pyomyositis within 14 days of initial ED visit). We described the initial diagnostic evaluation and ED management of children diagnosed with TS and variability between sites. RESULTS: We analyzed 6419 encounters from 37 hospitals. 62 (1.0%, 95%CI: 0.7-1.2%) children were diagnosed with a missed bacterial musculoskeletal infection. Children with missed infection were younger than those without (median age 2.6 vs. 4.6 years, p < 0.01). Serum laboratory testing was performed in 76% of encounters with minimal variation across sites. There was significant variation in the rates of hip ultrasound by site (2 to 92%), which has increased in use over time (from 42% in 2016 to 62% in 2021). CONCLUSION: In this large observational study, missed bacterial musculoskeletal infection in children diagnosed with TS was rare but more common in younger children. The optimal combination of bloodwork and radiographic testing, especially ultrasound, to distinguish TS from more serious disease remains unclear.

Conformer-Specific Spectroscopy and IR-Induced Isomerization of a Model γ-Peptide: Ac-γ4-Phe-NHMe.

Single-conformation IR and UV spectroscopy of the prototypical capped γ-peptide Ac-γ4-Phe-NHMe (γ4F) was carried out under jet-cooled conditions in the gas phase in order to understand its innate conformational preferences in the absence of a solvent. We obtained conformer-specific IR and UV spectra and compared the results with calculations to make assignments and explore the differences between the γ2- and γ4-substituted molecules. We found four conformers of γ4F in our experiment. Three conformers form nine-membered hydrogen-bonded rings (C9) enclosed by an NH···O═C H-bond but differing in their phenyl ring positions (a, g+, and g-). The fourth conformer forms a strained seven-membered hydrogen-bonded ring in which the amide groups lie in a nominally anti-parallel arrangement stacked on top of one another (labeled S7). This conformer is a close analogue of the amide-stacked conformer (S) found previously in γ2F, in which the Phe side chain is substituted at the γ2 position, Ac-γ2-Phe-NHMe (J. Am. Chem. Soc. 2009, 131, 14243-14245). IR population transfer spectroscopy was used to determine the fractional abundances of the γ4F conformers in the expansion. A combination of force field and density functional theory calculations is used to map out the conformational potential energy surfaces for γ4F and compare it with its γ2F counterpart. Based on this analysis, the phenyl ring prefers to take up structures that facilitate NH···π interactions in γ4F or avoid phenyl interactions with the C═O group in γ2F. The disconnectivity graph for γ4F reveals separate basins associated with the C9 and amide-stacked conformational families, which are separated by a barrier of about 42 kJ/mol. The overall shape of the potential energy surface bears a resemblance to peptides and proteins that have a misfolding pathway that competes with the formation of the native structure.

Risk of malignancy following emergency department Bell's palsy diagnosis in children.

OBJECTIVE: To quantify the risk of malignancy following the emergency department (ED) diagnosis of Bell's Palsy (BP) using a large retrospective cohort. STUDY DESIGN: We performed a cohort study using the Pediatric Health Information System database. We included all children (6 months - 17 years) from 2011 to 2020 with an ED diagnosis of BP. We excluded children with previous neurologic chronic condition or malignancy diagnosed during or prior to the index visit. Our primary outcome was diagnosis of malignancy within 60 days following the index ED visit. We compared clinical characteristics between children with and without new-onset malignancy. RESULTS: Of 12,272 encounters for BP, 41 had a new oncologic diagnosis within 60 days (0.33%, 95% confidence interval [CI]: 0.25-0.45%). Median time to oncologic diagnosis was 22 days. Primary CNS malignancy (59%) and leukemia (17.1%) were the most common diagnoses. Younger children had a higher incidence of new oncologic diagnosis compared with older children. Incidences were 0.68% (95% CI 0.36-1.3%), 0.70% (95% CI 0.38-1.3%), 0.26% (95% CI 0.15-0.47%), and 0.21% (95% CI 0.12-0.37%) for children aged <2 years, 2-5 years, 6-11 years, and 12-17 years respectively. CONCLUSIONS: We found a small but potentially clinically significant rate of new-onset oncologic diagnosis within 60 days after BP diagnosis in the ED, especially in children younger than 5 years. Further studies of the diagnostic utility of laboratory testing or neuroimaging and the risk of empiric steroids in children with BP are needed.

Conformer-Specific and Diastereomer-Specific Spectroscopy of αßα Synthetic Foldamers: Ac-Ala-ßACHC-Ala-NHBn.

The folding propensities of a capped, cyclically constrained, mixed α/ß diastereomer pair, ( SRSS) Ac-Ala-ßACHC-Ala-NHBn (hereafter RS) and ( SSRS) Ac-Ala-ßACHC-Ala-NHBn ( SR), have been studied in a molecular beam using single-conformation spectroscopic techniques. These α/ß-tripeptides contain a cyclohexane ring across each Cα -Cß bond, at which positions their stereochemistries differ. This cyclic constraint requires any stable species to adopt one of two ACHC configurations: equatorial C═O/axial NH or equatorial NH/axial C═O. Resonant two-photon ionization (R2PI) and infrared-ultraviolet hole-burning (IR-UV HB) spectroscopy were used in the S0-S1 region of the UV chromophore, revealing the presence of three unique conformational isomers of RS and two of SR. Resonant ion-dip infrared spectra were recorded in both the NH stretch (3200-3500 cm-1) and the amide I (1600-1800 cm-1) regions. These experimental vibrational frequencies were compared with the scaled calculated normal-mode frequencies from density functional theory at the M05-2X/6-31+G(d) level of theory, leading to structural assignments of the observed conformations. The RS diastereomer is known in crystalline form to preferentially form a C11/C9 mixed helix, in which alternating hydrogen bonds are arranged in near antiparallel orientation. This structure is preserved in one of the main conformers observed in the gas phase but is in competition with both a tightly folded C7eq/C12/C8/C7eq structure, in which all four amide NH groups and four C═O groups are engaged in hydrogen bonding, as well as a cap influenced C7eq/NH···π/C11 structure. The SR diastereomer is destabilized by inducing backbone dihedral angles that lie outside the typical Ramachandran angles. This diastereomer also forms a C11/C9 mixed helix as well as a cap influenced bifurcated C7ax-C11/NH···π/C7eq structure as the global energy minimum. Assigned structures are compared with the reported crystal structure of analogous α/ß-tripeptides, and disconnectivity graphs are presented to give an overview of the complicated potential energy surface of this tripeptide diastereomer pair.

Inherent Conformational Preferences of Ac-Gln-Gln-NHBn: Sidechain Hydrogen Bonding Supports a ß-Turn in the Gas Phase.

Gas-phase single-conformation spectroscopy is used to study Ac-Gln-Gln-NHBn in order to probe the interplay between sidechain hydrogen bonding and backbone conformational preferences. This small, amide-rich peptide offers many possibilities for backbone-backbone, sidechain-backbone, and sidechain-sidechain interactions. The major conformer observed experimentally features a type-I ß-turn with a canonical 10-membered ring C=O-H-N hydrogen bond between backbone amide groups. In addition, the C=O group of each Gln sidechain participates in a seven-membered ring hydrogen bond with the backbone NH of the same residue. Thus, sidechain hydrogen-bonding potential is satisfied in a manner that is consistent with and stabilizes the ß-turn secondary structure. This turn-forming propensity may be relevant to pathogenic amyloid formation by polyglutamine segments in human proteins.

Conformation-specific spectroscopy of capped glutamine-containing peptides: role of a single glutamine residue on peptide backbone preferences.

The conformational preferences of a series of short, aromatic-capped, glutamine-containing peptides have been studied under jet-cooled conditions in the gas phase. This work seeks a bottom-up understanding of the role played by glutamine residues in directing peptide structures that lead to neurodegenerative diseases. Resonant ion-dip infrared (RIDIR) spectroscopy is used to record single-conformation infrared spectra in the NH stretch, amide I and amide II regions. Comparison of the experimental spectra with the predictions of calculations carried out at the DFT M05-2X/6-31+G(d) level of theory lead to firm assignments for the H-bonding architectures of a total of eight conformers of four molecules, including three in Z-Gln-OH, one in Z-Gln-NHMe, three in Ac-Gln-NHBn, and one in Ac-Ala-Gln-NHBn. The Gln side chain engages actively in forming H-bonds with nearest-neighbor amide groups, forming C8 H-bonds to the C-terminal side, C9 H-bonds to the N-terminal side, and an amide-stacked geometry, all with an extended (C5) peptide backbone about the Gln residue. The Gln side chain also stabilizes an inverse γ-turn in the peptide backbone by forming a pair of H-bonds that bridge the γ-turn and stabilize it. Finally, the entire conformer population of Ac-Ala-Gln-NHBn is funneled into a single structure that incorporates the peptide backbone in a type I ß-turn, stabilized by the Gln side chain forming a C7 H-bond to the central amide group in the ß-turn not otherwise involved in a hydrogen bond. This ß-turn backbone structure is nearly identical to that observed in a series of X-(AQ)-Y ß-turns in the protein data bank, demonstrating that the gas-phase structure is robust to perturbations imposed by the crystalline protein environment.

Ultrafast Photoprotecting Sunscreens in Natural Plants.

We explore the ultrafast photoprotective properties of a series of sinapic acid derivatives in a range of solvents, utilizing femtosecond transient electronic absorption spectroscopy. We find that a primary relaxation mechanism displayed by the plant sunscreen sinapoyl malate and other related molecular species may be understood as a multistep process involving internal conversion of the initially photoexcited 1(1)ππ* state along a trans-cis photoisomerization coordinate, leading to the repopulation of the original trans ground-state isomer or the formation of a stable cis isomer.

Local Mode Approach to OH Stretch Spectra of Benzene-(H2O)n Clusters, n = 2-7.

Isomer-specific resonant ion-dip infrared spectra are presented for benzene-water (Bz-(H2O)n) clusters with two to seven water molecules. Local mode Hamiltonians based on scaled M06-2X/6-311++G(2d,p) density functional calculations are presented that accurately model the spectra across the entire OH stretch region (3000-3750 cm(-1)). The model Hamiltonians include the contribution from the water bend overtone and an empirical parameter for the local OH stretch-bend Fermi coupling. The inclusion of this coupling is necessary for accurate modeling of the infrared spectra of clusters with more than three water molecules. For the cyclic water clusters (n = 3-5), the benzene molecule perturbs the system in a characteristic way, distorting the cycle, splitting degeneracies, and turning on previously forbidden transitions. The local OH stretch site frequencies and H···OH hydrogen bond lengths follow a pattern based on the each water monomer's proximity to benzene. The patterns observed for these cyclic water clusters provide insight into benzene's effects on the three-dimensional hydrogen-bonded networks present in water hexamer and heptamer structures, which also have their spectra dramatically altered from their pure water counterparts.

Isomer-Specific Spectroscopy of Benzene-(H2O)n, n = 6,7: Benzene's Role in Reshaping Water's Three-Dimensional Networks.

The water hexamer and heptamer are the smallest sized water clusters that support three-dimensional hydrogen-bonded networks, with several competing structures that could be altered by interactions with a solute. Using infrared-ultraviolet double resonance spectroscopy, we record isomer-specific OH stretch infrared spectra of gas-phase benzene-(H2O)(6,7) clusters that demonstrate benzene's surprising role in reshaping (H2O)(6,7). The single observed isomer of benzene-(H2O)6 incorporates an inverted book structure rather than the cage or prism. The main conformer of benzene-(H2O)7 is an inserted-cubic structure in which benzene replaces one water molecule in the S4-symmetry cube of the water octamer, inserting itself into the water cluster by engaging as a π H-bond acceptor with one water and via C-H···O donor interactions with two others. The corresponding D(2d)-symmetry inserted-cube structure is not observed, consistent with the calculated energetic preference for the S4 over the D(2d) inserted cube. A reduced-dimension model that incorporates stretch-bend Fermi resonance accounts for the spectra in detail and sheds light on the hydrogen-bonding networks themselves and on the perturbations imposed on them by benzene.

Binding water to a PEG-linked flexible bichromophore: IR spectra of diphenoxyethane-(H2O)n clusters, n = 2-4.

The single-conformation infrared (IR) and ultraviolet (UV) spectroscopies of neutral 1,2-diphenoxyethane-(H2O)n clusters with n = 2-4 (labeled henceforth as 1:n) have been studied in a molecular beam using a combination of resonant two-photon ionization, IR-UV holeburning, and resonant ion-dip infrared (RIDIR) spectroscopies. Ground state RIDIR spectra in the OH and CH stretch regions were used to provide firm assignments for the structures of the clusters by comparing the experimental spectra with the predictions of calculations carried out at the density functional M05-2X/6-31+G(d) level of theory. At all sizes in this range, the water molecules form water clusters in which all water molecules engage in a single H-bonded network. Selective binding to the tgt monomer conformer of 1,2-diphenoxyethane (C6H5-O-CH2-CH2-O-C6H5, DPOE) occurs, since this conformer provides a binding pocket in which the two ether oxygens and two phenyl ring π clouds can be involved in stabilizing the water cluster. The 1:2 cluster incorporates a water dimer "chain" bound to DPOE much as it is in the 1:1 complex [E. G. Buchanan et al., J. Phys. Chem. Lett. 4, 1644 (2013)], with primary attachment via a double-donor water that bridges the ether oxygen of one phenoxy group and the π cloud of the other. Two conformers of the 1:3 cluster are observed and characterized, one that extends the water chain to a third molecule (1:3 chain) and the other incorporating a water trimer cycle (1:3 cycle). A cyclic water structure is also observed for the 1:4 cluster. These structural characterizations provide a necessary foundation for studies of the perturbations imposed on the two close-lying S1/S2 excited states of DPOE considered in the adjoining paper [P. S. Walsh et al., J. Chem. Phys. 142, 154304 (2015)].

Solvent-mediated internal conversion in diphenoxyethane-(H2O)n clusters, n = 2-4.

1,2-diphenoxyethane (DPOE) is a flexible bichromophore whose excited states come in close-lying pairs whose splitting and vibronic coupling can be modulated by solvent. Building on the ground state infrared spectroscopy of DPOE-(H2O)n clusters with n = 2-4 from the adjoining paper [Walsh et al., J. Chem. Phys. 142, 154303 (2015)], the present work focuses on the vibronic and excited state infrared spectroscopies of the clusters. The type and degree of asymmetry of the water cluster binding to DPOE is reflected in the variation in the magnitude of the S1/S2 splitting with cluster size. Excited state resonant ion-dip infrared spectroscopy was performed at the electronic origins of the first two excited states in order to explore how the water clusters' OH stretch spectra report on the nature of the two excited states, and the interaction of the S2 state with nearby S1 vibronic levels mediated by the water clusters. The data set, when taken as a whole, provides a state-to-state view of internal conversion and the role of solvent in mediating conversion of electronic excitation between two chromophores, providing a molecular-scale view of Kasha's rule.