Leo H. Koole

Intramolecular base–backbone association in 8-bromo-2′,3′-O-isopropylidene-adenosine. Detection of an O(5′)–H ⋯ N(3) hydrogen bond via a long range H(5″)–N(3) spin–spin coupling

A completely rigid conformation is found for the syn-nucleoside 8-bromo-2′,3′-O-isopropylidene-adenosine in apolar solvents, which is due to an effective O(5′)–H ⋯ N(3) hydrogen bond, as is demonstrated by a substantial N(3) quadrupolar broadening of the H(5″) resonances in the 1H n.m.r. spectra.

Flexible Coils with a Drug-Releasing Hydrophilic Coating: A New Platform for Controlled Delivery of Drugs to the Eye?

Delivery of drugs to the front-side of the eye is routinely done through eye drops. It is known that approximately 80% of each eye-drop is lost, as a result of rapid clearance of the tear fluid via the naso-lacrymal canal. Consequently, repeated administration through several droplets is usually necessary to achieve a desired effect, such as widening of the pupil prior to corneal surgery. A new ocular drug delivery device was studied. The new device is believed to provide a basis for a more convenient and efficient method for ocular drug delivery. The device is a metallic coil with a hydrophilic, drug-containing polymeric coating. The coil is placed in the conjuctival fornix (under the lower eye-lid) and the drug is slowly released by diffusion into the tear fluid. The capacity of the device could be increased by using the lumen of the coils as a depot for the drug to be released. Preliminary experiments with the new device were performed largely in vitro and in vivo. The latter experiments involved the release of a fluorescent dye and atropine (a potent mydriatic agent) in the eye of several healthy volunteers. The first results obtained with the new device indicate its potential utility. More research and development work is required to define the optimal design of the coil in order to minimize the risk of irritation. Furthermore, the parameters that define the kinetics of the intraocular drug release must be defined and optimized with respect to the exact application.

Determination of the nature of the conformational transmission effect in pentacoordinated phosphorus compounds

Abstract A high resolution 1HNMR study of several 4- and 5-coordinated (TBP) phosphorus compounds enabled us to determine the nature of the conformational transmission effect, which describes the influence of the phosphorus coordination on the molecular conformation. Of great use was the accurate determination of the J POMe coupling constant, with which the pseudorotational equilibrium around the pentacoordinated phosphorus can be described. It was determined that conformational transmission is purely electrostatic in origin, due to a larger charge density in the axis of the TBP structure. These findings were corroborated with quantumchemical calculations.