Self Association and Cyclodextrin Solubilization of NSAIDs

The phase solubility profiles with HPCD of thesodium salt of the NSAIDs(non-steriodal anti-inflammatory drugs) ibuprofen anddiflunisal were studied. Theslopes of the phase solubility diagrams were determinedfor the sodium salt of ibuprofenat pH 6.1, 6.3 and 6.7, and for the sodium salt ofdiflunisal at pH 6.1 and 8.4. In allcases the slope of the phase solubility diagram wasgreater than unity. These resultssuggested that the stoichiometry of the complex formedwas greater than unity withrespect to the drug. However molecular modeling, NMRand UV studies clearlyshowed that the complex stoichiometry was 1:1. Theseconflicting results can beexplained by applying the theory developed for micellarforming compounds. Thusthe solubilization of the drugs is due partially frominclusion complex formation andpartially from solubilization by aggregation. Wehave therefore demonstrated that thesolubility of drugs in a cyclodextrin solution isexplained not only by inclusioncomplex formation but also by non-inclusion associationof the uncomplexed drugwith the complex.     

Multi-mode transport through a quantum nanowire with two embedded dots

We investigate the conductance of a quantum wire with two embedded quantum dots using a T-matrix approach based on the Lippmann-Schwinger formalism. The quantum dots are represented by a quantum well with Gaussian shape and the wire is two-dimensional with parabolic confinement in the transverse direction. In a broad wire the transport can assume a strong nonadiabatic character and the conductance manifests effects caused by intertwined inter- and intra-dot processes that are identified by analysis of the “nearfield” probability distribution of the transported electrons.     

The Effects of Cyclodextrins on Hydrocortisone Permeability Through Semi-Permeable Membranes

Determinations of drug fluxes through semi-permeable cellophanemembranes are used to evaluate cyclodextrin complexes and cyclodextrin containingdrug formulations. In the present study we investigated how the cyclodextrin concentration,the membrane thickness and the molecular weight cut off (MWCO) of the membraneinfluence drug fluxes. The cyclodextrin used was 2-hydroxypropyl--cyclodextrin(HP--CD) and the sample drug was hydrocortisone. The MWCO ofthe membranes ranged from 500 to 14,000 and the HP--CD concentrationranged from 0 to 25% (w/v). The hydrocortisone flux from saturated solutions through the MWCO 500 membrane was unaffected by the cyclodextrin concentration. When MWCO of the membrane was greater than the molecular weight of the complex the flux fromsolutions saturated with hydrocortisone increased with increasing HP--CD concentration.This increase showed negative deviation from linearity. When the flux was correctedfor the viscosity increase with increasing HP--CD concentration then the fluxpattern could be described on the basis of Fick's first law and Stokes–Einsteinequation. However the flux did not correlate with the viscosity when it was increasedby adding polymer to the saturated drug solutions. It was shown that the observed fluxpattern was consistent with self-association of cyclodextrin complexes in the aqueousdonor phase.     

Free solution mobility of DNA molecules containing variable numbers of cationic phosphoramidate internucleoside linkages

The free solution electrophoretic mobility of an 118-base pair DNA fragment containing zero, three, six or nine cationic phosphoramidate internucleoside linkages has been measured by capillary electrophoresis. The electrophoretic mobility decreases with the increasing number of cationic phosphoramidate linkages, as expected because of the reduced negative charge on the DNA molecules. The decrease in mobility is approximately linear for DNA molecules containing three and six cationic phosphoramidate linkages, but begins to level off when nine cationic phosphoramidate linkages have been added. The mobility also varies somewhat depending on whether the modified phosphoramidate linkages are located at the 5'- or 3'-end of the DNA molecule.     

Behaviour of inorganic and organic cations in the Debye–Hückel layer of DNA

Inorganic, monovalent cations (Li, Na, K, Rb, Cs), when present in the Debye–Hückel layer of DNA, are found to bind to the negatively charged groups of the helix solely on the basis of their charge/mass ratio. Thus, when an electric field is applied, the free mobility of the DNA is seen to increase from Li- to Cs-equilibrated DNAs, since the latter cation, having a weaker surface charge distribution and a larger physical size (in the non-hydrated state), is more loosely bound to the DNA helix, thus providing less screening of its negative charges. On the contrary, organic amines (Tris and a number of Good’s buffers) are found to bind not only via electrostatic interactions, but by additional bonds, notably H-bonds. In particular, Tris can form two H-bonds, with a purine and pyrimidine, respectively, and a third H-bond shared between the –OH groups of two adjacent Tris. Hence, these buffer components may be unwitting participants in reactions carried out in in vitro systems.     

Separation of double-stranded DNA in conventional and isoelectric buffers: studies on stability and separation performance

In the capillary electrophoresis of double-stranded DNA in isoelectric buffers, worsening of resolution was observed in electropherograms as a function of time passed from the preparation of the separation solution, which consisted of 0.7% hydroxypropylcellulose, HPC, Mr 10(6), diluted in 150 mM histidine buffer. The DNA standards used were: kilobase pair-ladder, Marker V and Marker VI. In order to understand what happens in the histidine-HPC solution with ageing, the absorbance spectrum (200-500 nm), the conductivity and the pH of the solutions as a function of time were monitored. Fresh His gave a distinct peak at 206 nm. For all the solutions a significant diminution in the maximum absorbance value at 206 nm was observed as a function of ageing, with the concomitant appearance of a peak at 278 nm as the solutions became older. Also the conductivity increases dramatically with the ageing of the solutions and seemed to reach a plateau after ca. 40 days. In concomitance with the conductivity increments with time, the pH of the His solution (isoelectric point, pI=7.6) grew slowly up to pH 7.9; these combined data indicated that a new species contributing to the conductivity and altering the pH was formed from the His molecule, suggesting that His degraded in time. When the dipeptide His-Gly was used instead, a similar ageing phenomenon was observed, but with much reduced kinetics. Mass spectrometry, coupled to RP-HPLC, detected, in aged His solutions, in addition to intact His, two main degradation products: a 110.1 u species and a 93.2 u compound. The mass of the former coincides with the protonated species derived from the formation of a Schiff base on the alpha-amino group of His and subsequent decarboxylation without transformation of the final Schiff base into a chetonic group (a histamine-like molecule terminating with an imino, rather than with an amino group).