The binding properties of meso-tetrakis(N-methylpyridinium-4-yl)porphyrin (H(2)TMPyP) to RNA and DNA.RNA hybrid duplexes were studied by absorption and circular dichroism (CD) spectra. The duplexes studied were poly(rA).poly(rU), poly(rA).poly(dT), poly(rI).poly(rC), poly(rI).poly(dC), poly(rG).poly(rC), and poly(rG).poly(dC). The hypochromicity (about 40%) and the bathochromic shift (about 15 nm) of the porphyrin Soret absorption band upon binding were quite similar among the duplexes examined. The large bathochromic shift and hypochromicity suggested a significant perturbation in the porphyrin pi electrons upon binding. H(2)TMPyP was found to bind in a single step to poly(rI).poly(rC), poly(rG).poly(rC), and poly(rG).poly(dC) and in a multistep manner to poly(rA).poly(rU), poly(rA).poly(dT), and poly(rI).poly(dC). The induced CD spectra in the visible range suggested that the porphyrin preferred to bind to the RNA duplexes with self-stacking along the polymer surface and to the hybrids with intercalation, at least at higher duplex load. This implied a distinct conformational difference between the RNA duplexes and DNA.RNA hybrids, and a drug molecule is able to recognize the difference. The number of binding sites per base pairs (n), however, was very different among the RNA duplexes examined. We also found that the intensity of the bisignate-induced CD bands is proportional to the n value. This suggested that the transition moments on the neighboring porphyrins are interacting considerably with each other to produce intense induced CD peaks.

No abstract

No abstract

No abstract

In a previous study, the enhancing effects of a series of 1-alkyl-2-pyrrolidones (APs; 1-ethyl, 1-butyl, 1-hexyl, and 1-octyl-2-pyrrolidone) on the transport of steroidal permeants across hairless mouse skin were investigated via a parallel pathway skin model. Isoenhancement concentration conditions were deduced under which different APs induce essentially the same transport enhancement for the lipoidal pathway of the stratum corneum (s.c.). As a continuing effort to understand the mechanism of action of permeation enhancers, the influence of the APs on permeant partitioning into hairless mouse s.c. was investigated under the isoenhancement concentration conditions using beta-estradiol (E2 beta) as the model permeant. The amount of E2 beta uptake into s.c. was found to be essentially the same for all the APs under these isoenhancement conditions. This result suggests that inducing a higher partitioning tendency for E2 beta into the lipoidal pathway of hairless mouse s.c. is a principal mechanism of action of the APs in enhancing transdermal transport. The uptake of the APs into s.c. lipoidal domains was also determined, and the results show only a modest (approximately 2-fold) increase in the uptake of the APs in going from 1-ethyl-to 1-octyl-2-pyrrolidone under isoenhancement conditions. This indicates the potency of the APs as permeation enhancers is only very modestly dependent upon the alkyl chain length in this chain length region when compared at concentrations in the microenvironment where the action occurs in the lipid domains.