Computational and Experimental Studies of Non-Covalent Interactions: Characterization of CH...π Interactions and Structure of 1,1-Difluoroethylene...Carbon Dioxide

Weakly bound CH/π interactions, due to the abundance of C-H bonds and π systems that exist in larger organic molecules, are an important driving force in the construction of biomacromolecules, supramolecular assemblies and crystal packing of organic compounds. To assist in the characterization of CH/π interactions, a density functional theory (DFT) study has been conducted to determine a quick and cheap method for accurate determination of the binding energy and rotational constants for CH/π interactions. Seven complexes were used in this study: five benzene-HY complexes (where Y= C≡CH, Cl, F, Br and C≡N) and two fluorobenzene-HY complexes (where Y= C≡CH and Cl). The two DFT levels, ωB97XD and M06-2X, were found to precisely replicate the binding energies for the benzene and fluorobenzene complexes compared to the gold standard theory level, coupled cluster theory (CCSD(T)) with a complete basis set (CBS) extrapolation. ωB97XD is the best level for calculating binding energies when the optimization is BSSE corrected, and M06-2X is best when the optimization is BSSE uncorrected. For prediction of rotational constants, ωB97XD was the best overall DF T level, performing better for the benzene complexes when BSSE uncorrected, but was more accurate for the fluorobenzene complexes when BSSE corrected. Overall ωB97XD is recommended as the best DFT level for predicting binding energies and rotational constants for CH/π interactions. The concentration of CO₂ in the atmosphere has increased dramatically over the years as a result of burning of coal, natural gas and oil. To reduce the excess CO₂ in the atmosphere, CO₂ capturing devices (that rely on non-covalent interactions to bind the CO₂) have been created. One way to recycle the captured CO₂ is to use it as a green supercritical solvent. Supercritical CO₂ has unique properties that can allow it to dissolve molecules containing fluorine atoms by mechanisms that are not fully understood. With the aim of understanding interactions between fluorinated species and CO₂, a study of 1,1-difluoroethylene-CO₂ was done. The experimental structure of 1,1-difluoroethylene-CO₂ was determined from the experimental rotational constants A= 5696.6440(9) MHz, B= 1121.85748(24) MHz and C= 939.4186(4) MHz. The structure of 1,1-difluoroethylene-CO₂ followed the same trend as other fluorinated ethylene-CO₂ complexes, with the CO₂ molecule interacting in the same plane as the fluoroethylene. The fluorinated ethylene-CO₂ complexes have similar parameters such as a C--F interaction distance ranging from 2.90 Å to 2.95 Å, and an F--C=O angle that ranges from 83° to 89°. Lastly, a modification was made to the chirped-pulse Fourier-transform microwave (CP-FTMW) spectrometer by the addition of a mixing controller. The mixing controller was constructed to improve the intensity of the transitions for dimers, radicals, and ionic species by allowing variation of sample concentration and pressure in real time . Using the mixing controller, the radical, C₄H∙, and the dimer, fluorobenzene-acetylene, were observed for the first time on the CP-FTMW spectrometer. The mixing controller has made it possible to observe other radical/ionic species on the CP-FTMW spectrometer (such as C5H∙ radical)

Computational and Experimental Studies of Non-Covalent Interactions: Characterization of CH...π Interactions and Structure of 1,1-Difluoroethylene...Carbon Dioxide

Weakly bound CH/π interactions, due to the abundance of C-H bonds and π systems that exist in larger organic molecules, are an important driving force in the construction of biomacromolecules, supramolecular assemblies and crystal packing of organic compounds. To assist in the characterization of CH/π interactions, a density functional theory (DFT) study has been conducted to determine a quick and cheap method for accurate determination of the binding energy and rotational constants for CH/π interactions. Seven complexes were used in this study: five benzene-HY complexes (where Y= C≡CH, Cl, F, Br and C≡N) and two fluorobenzene-HY complexes (where Y= C≡CH and Cl). The two DFT levels, ωB97XD and M06-2X, were found to precisely replicate the binding energies for the benzene and fluorobenzene complexes compared to the gold standard theory level, coupled cluster theory (CCSD(T)) with a complete basis set (CBS) extrapolation. ωB97XD is the best level for calculating binding energies when the optimization is BSSE corrected, and M06-2X is best when the optimization is BSSE uncorrected. For prediction of rotational constants, ωB97XD was the best overall DF T level, performing better for the benzene complexes when BSSE uncorrected, but was more accurate for the fluorobenzene complexes when BSSE corrected. Overall ωB97XD is recommended as the best DFT level for predicting binding energies and rotational constants for CH/π interactions. The concentration of CO₂ in the atmosphere has increased dramatically over the years as a result of burning of coal, natural gas and oil. To reduce the excess CO₂ in the atmosphere, CO₂ capturing devices (that rely on non-covalent interactions to bind the CO₂) have been created. One way to recycle the captured CO₂ is to use it as a green supercritical solvent. Supercritical CO₂ has unique properties that can allow it to dissolve molecules containing fluorine atoms by mechanisms that are not fully understood. With the aim of understanding interactions between fluorinated species and CO₂, a study of 1,1-difluoroethylene-CO₂ was done. The experimental structure of 1,1-difluoroethylene-CO₂ was determined from the experimental rotational constants A= 5696.6440(9) MHz, B= 1121.85748(24) MHz and C= 939.4186(4) MHz. The structure of 1,1-difluoroethylene-CO₂ followed the same trend as other fluorinated ethylene-CO₂ complexes, with the CO₂ molecule interacting in the same plane as the fluoroethylene. The fluorinated ethylene-CO₂ complexes have similar parameters such as a C--F interaction distance ranging from 2.90 Å to 2.95 Å, and an F--C=O angle that ranges from 83° to 89°. Lastly, a modification was made to the chirped-pulse Fourier-transform microwave (CP-FTMW) spectrometer by the addition of a mixing controller. The mixing controller was constructed to improve the intensity of the transitions for dimers, radicals, and ionic species by allowing variation of sample concentration and pressure in real time . Using the mixing controller, the radical, C₄H∙, and the dimer, fluorobenzene-acetylene, were observed for the first time on the CP-FTMW spectrometer. The mixing controller has made it possible to observe other radical/ionic species on the CP-FTMW spectrometer (such as C5H∙ radical)

Sleep disturbance and serum ferritin levels associate with high impulsivity and impulse control disorders in male Parkinson\u27s Disease patients

Impulse control disorders (ICDs) occur in a subset of Parkinson’s disease (PD) patients on dopaminergic medications however there are currently no reliable markers to identify patients at risk. Sleep disturbances are more common in patients with an ICD. Serum ferritin levels have been associated with PD disease stage and progression, but have not previously been associated with impulsivity levels. The objective of this study was to determine if serum ferritin levels and sleep disturbance are associated with high traits of impulsivity and ICD in a cohort of PD patients attending a movement disorders clinic. This study assessed impulsiveness in 87 PD patients using the Barratt Impulsiveness Scale. Severity of sleep disturbance was determined using the sleep-related items of the MDS-UPDRS. Serum ferritin, iron and transferrin levels were measured in patients, as well as 36 age-matched healthy controls. Serum ferritin levels were significantly elevated in male PD patients in the high impulsivity group compared to patients in the low (p=.022) and normal range groups (p=.024) and showed a linear increase across the three groups. Sleep disturbance also demonstrated a linear trend, which was most severe in the high impulsivity group (p=.030). A subgroup of 11 male PD patients who fulfilled the DSM-5 criteria for an ICD had significantly higher ferritin levels and more severe sleep disturbance when compared with the remaining male PD cohort. Serum ferritin levels and sleep disturbance severity are highlighted as potential markers for abnormal impulsivity and ICD in PD patients

Extended Timed Up and Go assessment as a clinical indicator of cognitive state in Parkinson\u27s disease

Objective: To evaluate a modified extended Timed Up and Go (extended-TUG) assessment against a panel of validated clinical assessments, as an indicator of Parkinson’s disease (PD) severity and cognitive impairment. Methods: Eighty-seven participants with idiopathic PD were sequentially recruited from a Movement Disorders Clinic. An extended-TUG assessment was employed which required participants to stand from a seated position, walk in a straight line for 7 metres, turn 180 degrees and then return to the start, in a seated position. The extended-TUG assessment duration was correlated to a panel of clinical assessments, including the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Quality of Life (PDQ-39), Scales for Outcomes in Parkinson’s disease (SCOPA-Cog), revised Addenbrooke’s Cognitive Index (ACE-R) and Barratt’s Impulsivity Scale 11 (BIS-11). Results: Extended-TUG time was significantly correlated to MDS-UPDRS III score and to SCOPA-Cog, ACE-R (p\u3c0.001) and PDQ-39 scores (p\u3c0.01). Generalized linear models determined the extended-TUG to be a sole variable in predicting ACE-R or SCOPA-Cog scores. Patients in the fastest extended-TUG tertile were predicted to perform 8.3 and 13.4 points better in the SCOPA-Cog and ACE-R assessments, respectively, than the slowest group. Patients who exceeded the dementia cut-off scores with these instruments exhibited significantly longer extended-TUG times. Conclusions: Extended-TUG performance appears to be a useful indicator of cognition as well as motor function and quality of life in PD, and warrants further evaluation as a first line assessment tool to monitor disease severity and response to treatment. Poor extended-TUG performance may identify patients without overt cognitive impairment form whom cognitive assessment is needed

Peptide immunotherapy for childhood allergy - addressing translational challenges

Allergic sensitisation usually begins early in life. The number of allergens a patient is sensitised to can increase over time and the development of additional allergic conditions is increasingly recognised. Targeting allergic disease in childhood is thus likely to be the most efficacious means of reducing the overall burden of allergic disease. Specific immunotherapy involves administering protein allergen to tolerise allergen reactive CD4+ T cells, thought key in driving allergic responses. Yet specific immunotherapy risks allergic reactions including anaphylaxis as a consequence of preformed allergen-specific IgE antibodies binding to the protein, subsequent cross-linking and mast cell degranulation. CD4+ T cells direct their responses to short "immunodominant" peptides within the allergen. Such peptides can be given therapeutically to induce T cell tolerance without facilitating IgE cross-linking. Peptide immunotherapy (PIT) offers attractive treatment potential for allergic disease. However, PIT has not yet been shown to be effective in children. This review discusses the immunological mechanisms implicated in PIT and briefly covers outcomes from adult PIT trials. This provides a context for discussion of the challenges for the application of PIT, both generally and more specifically in relation to children

Notes

Notes by John M. Anderton, B. M. Apker, J. V. Wilcox, Leonard Boykin, Jr., John J. Broderick, Jr., Thomas F. Broden, Robert F. Burns, John E. Cosgrove, James K. Sugnet, and James D. Sullivan