The Contribution of the Activation Entropy to the Gas-Phase Stability of Modified Nucleic Acid Duplexes

Tricyclo-DNA (tcDNA) is a sugar-modified analogue of DNA currently tested for the treatment of Duchenne muscular dystrophy in an antisense approach. Tandem mass spectrometry plays a key role in modern medical diagnostics and has become a widespread technique for the structure elucidation and quantification of antisense oligonucleotides. Herein, mechanistic aspects of the fragmentation of tcDNA are discussed, which lay the basis for reliable sequencing and quantification of the antisense oligonucleotide. Excellent selectivity of tcDNA for complementary RNA is demonstrated in direct competition experiments. Moreover, the kinetic stability and fragmentation pattern of matched and mismatched tcDNA heteroduplexes were investigated and compared with non-modified DNA and RNA duplexes. Although the separation of the constituting strands is the entropy-favored fragmentation pathway of all nucleic acid duplexes, it was found to be only a minor pathway of tcDNA duplexes. The modified hybrid duplexes preferentially undergo neutral base loss and backbone cleavage. This difference is due to the low activation entropy for the strand dissociation of modified duplexes that arises from the conformational constraint of the tc-sugar-moiety. The low activation entropy results in a relatively high free activation enthalpy for the dissociation comparable to the free activation enthalpy of the alternative reaction pathway, the release of a nucleobase. The gas-phase behavior of tcDNA duplexes illustrates the impact of the activation entropy on the fragmentation kinetics and suggests that tandem mass spectrometric experiments are not suited to determine the relative stability of different types of nucleic acid duplexes.

Stability of Cs-Ionsiv in Portland cement blends for radioactive waste disposal

The suitability of Portland cement blends for encapsulation of Cs-Ionsiv in a monolithic wasteform was investigated. No evidence of reaction or dissolution of the Cs-Ionsiv in the cementitious environment was found by scanning electron microscopy and X-ray diffraction. However, a small fraction (≤1.6 wt%) of the Cs inventory was released from the encapsulated Ionsiv during leaching experiments carried out on hydrated samples. Cs release was enhanced by exchange of K and Na present in the cementitious pore water. Cement systems lower in K and Na, such as slag based blends, showed lower Cs release than the fly ash based analogues. © 2010 Materials Research Society.

Two details of ships.

[From Jasper Cropsey Sketch book, 1855-1856]

Hydraulics and stability of five Texas inlets /

"January 1981."

Growth and stability of rural economies in the 1980s : differences among counties /

Mode of access: Internet.

Hydraulics and stability of tidal inlets /

Issued August 1977.

The stability of air bubbles in the sea and the effect of bubbles and particles in the extinction of sound and light in sea water /

Mode of access: Internet.

A laboratory study of the stability of sand-filled nylon bag breakwater structures /

"March 1977."

Model tests and numerical simulation of ship capsizing in following seas : final report for period December 1976 - October 1979 /

"Report no. CG-D-08-81."

Guidelines for improving the stability of headlamp aim. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Stability of rubble-mound breakwater Lahaina Harbor, Hawaii : hydraulic model investigation /

Cover title.