Coherent vibrational and dissociation dynamics of polyatomic radical cations

The ultrafast dynamics of polyatomic radical cat- ions contribute to important processes including energy transfer in photovoltaics, electron transfer in photocataly- sis, radiation-induced DNA damage, and chemical reac- tions in the upper atmosphere and space. Probing these dynamics in the gas phase is challenging due to the rapid dissociation of polyatomic radical cations following elec- tron removal, which arises from excess electronic excita- tion of the molecule during the ionization process. This Concept article introduces the reader to how the pump- probe technique of femtosecond time-resolved mass spectrometry (FTRMS) can overcome this challenge to capture coherent vibrational dynamics on the femtosec- ond timescale in polyatomic radical cations and enable the analysis of their dissociation pathways. Examples of FTRMS applied to three families of polyatomic radical cat- ions are discussed

Study of foldable elastic tubes for large space structure applications, phase 1

Structural members that might be suitable for strain energy deployable structures, are discussed with emphasis on a thin-walled cylindrical tube with a cross-section that is called 'bi-convex'. The design of bi-convex tube test specimens and their fabrication are described as well as the design and construction of a special purpose testing machine to determine the deployment characteristics. The results of the first series of tests were quite mixed, but clearly revealed that since most of the specimens failed to deploy completely, due to a buckling problem, this type of tube requires some modification in order to be viable

Probing Coherent Vibrations of Organic Phosphonate Radical Cations with Femtosecond Time-Resolved Mass Spectrometry

Organic phosphates and phosphonates are present in a number of cellular components that can be damaged by exposure to ionizing radiation. This work reports femtosecond time-resolved mass spectrometry (FTRMS) studies of three organic phosphonate radical cations that model the DNA sugar-phosphate backbone: dimethyl methylphosphonate (DMMP), diethyl methylphosphonate (DEMP), and diisopropyl methylphosphonate (DIMP). Upon ionization, each molecular radical cation exhibits unique oscillatory dynamics in its ion yields resulting from coherent vibrational excitation. DMMP has particularly well-resolved 45 fs (732 ± 28 cm−1) oscillations with a weak feature at 610–650 cm−1, while DIMP exhibits bimodal oscillations with a period of ∼55 fs and two frequency features at 554 ± 28 and 670–720 cm−1. In contrast, the oscillations in DEMP decay too rapidly for effective resolution. The low- and high-frequency oscillations in DMMP and DIMP are assigned to coherent excitation of the symmetric O–P–O bend and P–C stretch, respectively. The observation of the same ionization-induced coherently excited vibrations in related molecules suggests a possible common excitation pathway in ionized organophosphorus compounds of biological relevance, while the distinct oscillatory dynamics in each molecule points to the potential use of FTRMS to distinguish among fragment ions produced by related molecules

Conserved Vibrational Coherence in the Ultrafast Rearrangement of 2-Nitrotoluene Radical Cation

2-Nitrotoluene (2-NT) is a good model for both photolabile protecting groups for organic synthesis and the military explosive 2,4,6-trinitrotoluene (TNT). In addition to the direct C−NO2 bond-cleavage reaction that initiates detonation in TNT, 2-NT undergoes an H atom attack reaction common to the photolabile 2-nitrobenzyl group, which forms the aci-nitro tautomer. In this work, femtosecond pump−probe measure- ments with mass spectrometric detection and density functional theory (DFT) calculations demonstrate that the initially prepared vibrational coherence in the 2-NT radical cation (2- NT+) is preserved following H atom attack. Strong-field adiabatic ionization is used to prepare 2-NT+, which can overcome a modest 0.76 eV energy barrier to H atom attack to form the aci-nitro tautomer as soon as ∼20−60 fs after ionization. Once formed, the aci-nitro tautomer spontaneously loses −OH to form C7H6NO+, which exhibits distinctly faster oscillations in its ion yield (290 fs period) as compared to the 2-NT+ ion (380 fs period). The fast oscillations are attributed to the coherent torsional motion of the aci-nitro tautomer, which has a significantly faster computed torsional frequency (86.9 cm−1) than the 2- NT+ ion (47.9 cm−1). Additional DFT calculations identify reaction pathways leading to the formation of the dissociation products C7H6NO+, C7H7+, and C6H6N+. Collectively, these results reveal a rich picture of coherently and incoherently driven dissociation pathways in 2-NT+

Probing Coherent Vibrations of Organic Phosphonate Radical Cations with Femtosecond Time-Resolved Mass Spectrometry

Organic phosphates and phosphonates are present in a number of cellular components that can be damaged by exposure to ionizing radiation. This work reports femtosecond time-resolved mass spectrometry (FTRMS) studies of three organic phosphonate radical cations that model the DNA sugar-phosphate backbone: dimethyl methylphosphonate (DMMP), diethyl methylphosphonate (DEMP), and diisopropyl methylphosphonate (DIMP). Upon ionization, each molecular radical cation exhibits unique oscillatory dynamics in its ion yields resulting from coherent vibrational excitation. DMMP has particularly well-resolved 45 fs (732 ± 28 cm−1) oscillations with a weak feature at 610–650 cm−1, while DIMP exhibits bimodal oscillations with a period of ∼55 fs and two frequency features at 554 ± 28 and 670–720 cm−1. In contrast, the oscillations in DEMP decay too rapidly for effective resolution. The low- and high-frequency oscillations in DMMP and DIMP are assigned to coherent excitation of the symmetric O–P–O bend and P–C stretch, respectively. The observation of the same ionization-induced coherently excited vibrations in related molecules suggests a possible common excitation pathway in ionized organophosphorus compounds of biological relevance, while the distinct oscillatory dynamics in each molecule points to the potential use of FTRMS to distinguish among fragment ions produced by related molecules

Composite sodium alginate and chitosan based wafers for buccal delivery of macromolecules.

The objective of this study was to develop a composite buccal wafer for protein drug delivery. The polymeric vehicle used in this study combined chitosan and sodium alginate with bovine serum albumin (BSA) as a model drug. The wafers were obtained by freeze-drying gels of the polymers in well plates. Prior to the lyophilisation process, differential scanning calorimetry was performed to establish a suitable freeze-drying cycle. Preliminary characterization experiments were undertaken to select the optimum composite gel containing sodium alginate and chitosan in a 4:1 ratio respectively for drug loading. A second series of characterisation tests were performed on the drugloaded wafers prepared from gels containing 0.25 and 0.5 % w/w of BSA. The formulations were functionally characterised for swelling, mucoadhesive and drug dissolution properties. The morphology and crystallinity were investigated using a scanning electron microscope and X-ray diffractometer respectively. The results from drug dissolution studies over a two-hour period showed 66% and 31% cumulative drug release for the wafers obtained from gels containing 0.25 and 0.50 % w/w BSA respectively. These results show the feasibility of developing a sustained delivery system for macromolecules by combining chitosan and sodium alginate

Formulation development of a carrageenan based delivery system for buccal drug delivery using ibuprofen as a model drug

Solvent cast films are used as oral strips with potential to adhere to the mucosal surface, hydrate and deliver drugs across the buccal membrane. The objective of this study was the formulation development of bioadhesive films with optimum drug loading for buccal delivery. Films prepared from κ-carrageenan, poloxamer and polyethylene glycol or glycerol, were loaded with ibuprofen as a model water insoluble drug. The films were characterized using texture analysis (TA), hot stage microscopy (HSM), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), x-ray powder diffraction (XRPD), high performance liquid chromatography (HPLC) and in vitro drug dissolution. Optimized films were obtained from aqueous gels containing 2.5% w/w κ-carrageenan 911, 4% w/w poloxamer 407 and polyethylene glycol (PEG) 600 [5.5% w/w (non-drug loaded) and 6.5% w/w (drug loaded)]. A maximum of 0.8% w/w ibuprofen could be incorporated into the gels to obtain films with optimum characteristics. Texture analysis confirmed that optimum film flexibility was achieved from 5.5% w/w and 6.5% (w/w) of PEG 600 for blank films and ibuprofen loaded films respectively. TGA showed residual water content of the films as approximately 5%. DSC revealed a Tg for ibuprofen at −53.87°C, a unified Tm for PEG 600/poloxamer mixture at 32.74°C and the existence of ibuprofen in amorphous form, and confirmed by XRPD. Drug dissolution at a pH simulating that of saliva showed that amorphous ibuprofen was released from the films at a faster rate than the pure crystalline drug. The results show successful design of a carrageenan and poloxamer based drug delivery system with potential for buccal drug delivery and showed the conversion of crystalline ibuprofen to the amorphous form during film formation

Formulation, characterisation and stabilisation of buccal films for paediatric drug delivery of omeprazole

This study aimed to develop films for potential delivery of omeprazole (OME) via the buccal mucosa of paediatric patients. Films were prepared using hydroxypropylmethylcellulose (HPMC), methylcellulose (MC), sodium alginate (SA), carrageenan (CA) and metolose (MET) with polyethylene glycol (PEG 400) as plasticiser, OME (model drug) and L-arg (stabiliser). Gels (1% w/w) were prepared at 40°C using water and ethanol with PEG 400 (0–1% w/w) and dried in an oven (40°C). Optimised formulations containing OME and L-arg (1:1, 1:2 and 1:3) were prepared to investigate the stabilisation of the drug. Tensile properties (Texture analysis, TA), physical form (differential scanning calorimetry, DSC; X-ray diffraction, XRD; thermogravimetric analysis, TGA) and surface topography (scanning electron microscopy, SEM) were investigated. Based on the TA results, SA and MET films were chosen for OME loading and stabilisation studies as they showed a good balance between flexibility and toughness. Plasticised MET films were uniform and smooth whilst unplasticised films demonstrated rough lumpy surfaces. SA films prepared from aqueous gels showed some lumps on the surface, whereas SA films prepared from ethanolic gels were smooth and uniform. Drug-loaded gels showed that OME was unstable and therefore required addition of L-arg. The DSC and XRD suggested molecular dispersion of drug within the polymeric matrix. Plasticised (0.5% w/w PEG 400) MET films prepared from ethanolic (20% v/v) gels and containing OME: L-arg 1:2 showed the most ideal characteristics (transparency, ease of peeling and flexibility) and was selected for further investigation

Detection of viable Mycobacterium ulcerans in clinical samples by a novel combined 16S rRNA reverse transcriptase/IS2404 real-time qPCR assay.

Detection of Viable <em>Mycobacterium ulcerans</em> in Clinical Samples by a Novel Combined 16S rRNA Reverse Transcriptase/IS<em>2404</em> Real-Time qPCR Assa