ALBERT

Notes: Multiple small-angle neutron scattering was used to characterize the microstructure evolution of porous silica as a function of thermal processing. This new technique offers a statistically significant determination of microstructure morphology in the 0.08–10 μm range, which was previously inaccessible without increasing the resolution of the currently available scattering spectroscopy beamlines. All of the scatterers, which in the present work are pores within ceramic bodies, are measured whether they are open or closed. Earlier mercury porosimetry and nitrogen desorption measurements of the microporous silica system indicated that there are two major populations of pores in this material, differing in pore size by approximately an order of magnitude. In this work, it was found that densification during the intermediate stages of sintering is accompanied by coarsening to radii 〉 0.22 μm within the population of large pores in microporous silica. In the late stages of sintering, there are no detectable pores with radii 〉 0.08 μm, and radii of gyration equal to 33 and 28 nm were measured. Finally, Monte Carlo simulations were carried out to complement the neutron-scattering measurements, to predict the influence on the results of the bimodal distribution, and to explore the sensitivity of the multiple-scattering method.

Notes: Small-angle neutron scattering was used to study the structure of the dense cores of intact neurosecretory vesicles (NSV). Contrast-variation techniques were used to minimize the scattering due to vesicle membranes and emphasize that due to the cores. By examination of a suspension of NSV membranes along with the intact NSV, residual membrane scattering was suppressed. The resultant scattering is inconsistent with model calculations which assume that the dense state of the vesicle cores is achieved by random dense packing or crystallization of small globular particles. Rather, the data suggest that the core constituents exist in a disordered state, forming aggregates with radii of gyration significantly larger than 100 Å.

Notes: The binding of the antitumor agent CC-1065 to a variety of poly- and oligonucleotides was studied by electronic absorption, CD, and resistance to removal by Sephadex column chromatography. Competitive binding experiments between CC-1065 and netropsin were carried out with calf-thymus DNA, poly(dI-dC) · poly(dI-dC), poly(dI) · poly(dC), poly(rA) · poly(dT), poly(dA- dC) · poly(dG-dT), and poly(dA) · 2poly(dT). CC-1065 binds to polynucleotides by three mechanisms. In the first, CC-1065 binds only weakly, as judged by the induction of zero or very weak CD spectra and low resistance to extraction of drug from the polynucleotide by Sephadex chromatography. In the second and third mechanisms, CC-1065 binds strongly, as judged by the induction of two distinct, intense CD spectra and high resistance to extraction of drug from the polynucleotide, by Sephadex chromatography in both cases. The species bound by the second mechanism converts to that bound by the third mechanism with varying kinetics, which depend both on the base-pair sequence and composition of the polynucleotide. Competitive binding experiments with netropsin show that CC-1065 binds strongly in the minor groove of DNA by the second and third mechanisms of binding. Netropsin can displace CC-1065 that is bound by the second mechanism but not that bound by the third mechanism. CC-1065 binds preferentially to B-form duplex DNA and weakly (by the first binding mechanism) or not at all to RNA, DNA, and RNA-DNA polynucleotides which adopt the A-form conformation or to single-strand DNA. This correlation of strong binding of CC-1065 to B-form duplex DNA is consistent with x-ray data, which suggest an anomalous structure for poly(dI) · poly(rC), as compared with poly(rI) · poly(dC) (A-form) and poly(dI) · poly(dC) (B-form). The binding data indicate that poly(rA) · poly(dU) takes the B-form secondary structure like poly(rA) · poly(dT). Triple-stranded poly(dA) · 2poly(dT) and poly(dA) · 2poly(dU), which are considered to adopt the A-form conformation, bind CC-1065 strongly. Netropsin, which also shows a binding preference for B-form polynucleotides, also binds to poly(dA) · 2poly(dT) and occupies the same binding site as CC-1065. These binding studies are consistent with results of x-ray studies, which suggest that A-form triplex DNA retains some structural features of B-form DNA that are not present in A-form duplex DNA; i.e., the axial rise per nucleotide and the base tilt. Triple-stranded poly(dA) · 2poly(rU) does not bind CC-1065 strongly but has nearly the same conformation as poly(dA) · 2poly(dT) based on x-ray analysis. This suggests that the 2′-OH group of the poly(rU) strands interferes with CC-1065 binding to this polynucleotide. The same type of interference may occur for other RNA and DNA-RNA polynucleotides that bind CC-1065 weakly.