Exciplex and excimer molecular probes: detection of conformational flip in a myo-inositol chair

2-O-tert-Butyldimethylsilyl-4,6-bis-O-pyrenoyl-myo-inositol-1,3,5-orthoformate (6) and 2-O-tert-butyldimethylsilyl-4-O-[4-(dimethylamino)benzoyl]-6-O-pyrenoyl-myo-inositol-1,3,5-orthoacetate (10) adopt conformationally restricted unstable chairs with five axial substituents. In the symmetrical diester 6, the two pi-stacked pyrenoyl groups are electron acceptor-donor partners, giving a strong intramolecular excimer emission. In the mixed ester 10, the pyrenoyl group is the electron acceptor and the 4-(dimethylamino)benzoyl ester is the electron donor, giving a strong intramolecular exciplex emission. The conformation of the mixed ester 10 was assessed using 1H NMR spectroscopy (1H-NOESY) and computational studies. which showed the minimum inter-centroid distance between the two aromatic systems to be approximately 3.9 A. Upon addition of acid, the orthoformate/orthoacetate trigger in 6 and 10 was cleaved, which caused a switch of the conformation of the myo-inositol ring to the more stable penta-equatorial chair, leading to separation of the aromatic ester groups and loss of excimer and exciplex fluorescence, respectively. This study provides proof of principle for the development of novel fluorescent molecular probes.     

Radiosynthesis and reactivity of N-[11C]methyl carbamoylimidazole

Journal of Radioanalytical and Nuclear Chemistry - N-Methyl carbamoylimidazole is a safe and practical alternative to methyl isocyanate for carbamoylation reactions. We have developed a new...     

Adaptive Remodeling in the Elastase-Induced Rabbit Aneurysms

Background

Rupture of brain aneurysms is associated with high fatality and morbidity rates. Through remodeling of the collagen matrix, many aneurysms can remain unruptured for decades, despite an enlarging and evolving geometry.

Objective

Our objective was to explore this adaptive remodeling for the first time in an elastase induced aneurysm model in rabbits.

Methods

Saccular aneurysms were created in 22 New Zealand white rabbits and remodeling was assessed in tissue harvested 2, 4, 8 and 12 weeks after creation.

Results

The intramural principal stress ratio doubled after aneurysm creation due to increased longitudinal loads, triggering a remodeling response. A distinct wall layer with multi-directional collagen fibers developed between the media and adventitia as early as 2 weeks, and in all cases by 4 weeks with an average thickness of 50.6?±?14.3 μm. Collagen fibers in this layer were multi-directional (AI?=?0.56?±?0.15) with low tortuosity (1.08?±?0.02) compared with adjacent circumferentially aligned medial fibers (AI?=?0.78?±?0.12) and highly tortuous adventitial fibers (1.22?±?0.03). A second phase of remodeling replaced circumferentially aligned fibers in the inner media with longitudinal fibers. A structurally motivated constitutive model with both remodeling modes was introduced along with methodology for determining material parameters from mechanical testing and multiphoton imaging.

Conclusions

A new mechanism was identified by which aneurysm walls can rapidly adapt to changes in load, ensuring the structural integrity of the aneurysm until a slower process of medial reorganization occurs. The rabbit model can be used to evaluate therapies to increase aneurysm wall stability.

     

Nonlinear model and system identification of a capacitive dual-backplate MEMS microphone

This paper presents the nonlinear identification of a capacitive dual-backplate microelectromechanical systems (MEMS) microphone. First, a nonlinear lumped element model of the coupled electromechanical microphone dynamics is developed. Nonlinear finite element analyses are performed to verify the accuracy of the lumped linear and cubic stiffnesses of the diaphragm. In order to experimentally extract the system parameters, an approximate solution using the second-order multiple scales method is synthesized for a nonlinear microphone model, subject to an electrical step input. A nonlinear least-squares technique is then implemented to extract system parameters from laser vibrometry data of the diaphragm motion. The results indicate that the theoretical fundamental resonant frequency, damping ratio and nonlinear stiffness parameter agree with the corresponding extracted experimental parameters with 95% confidence interval estimates.     

Conformational probe: static quenching is reduced upon acid triggered ring flip of a myo-inositol derivative

The aromatic rings in 4-O-dabsyl-6-O-dansyl-myo-inositol-1,3,5-orthoformate (6) participate in electron transfer causing static quenching as detected by the absence of fluorescence. Upon addition of acid, the orthoformate lock is cleaved, with subsequent conformational change of the myo-inositol ring from penta-axial to the more stable penta-equatorial chair, which causes some increase in fluorescence due to spatial separation of fluorophore and a quencher and reduction in static quenching. In the case of 4,6-O-bisdansyl-myo-inositol-1,3,5-orthoformate (3), the acid-induced removal of the orthoformate lock leads to substantial change of fluorescence following spatial separation of two dansyl groups.