Small molecule penetration, resist

Viral infections continue to be significant causes of morbidity and mortality and at the same time continue to be resistant to treatment by small molecules. Avridine (6) is an antiviral compound which has shown some activity in a variety of animal tests apparently based upon its ability to stimulate a number of cells to produce the high molecular weight endogenous antiviral substance interferon. Thus, the compound is believed to operate indirectly by stimulating the body s own natural defenses against viral penetration into host cells. Avridine is synthesized by... 

This equation looks very similar to Eq. (23) for the draining function 0, The meaning, however, is different the function 0 is determined by the resistance of the penetration of small molecules (the solvent molecules) into the clouds of connected segments, while the interpenetration function results from the far more inhibited interpenetration of two connected segment clouds. Figure 8 elucidates the difference. 

Solubility Similarly, small molecules cannot penetrate the crystalline domains, which must be melted before the polymer, will dissolve.. Solvent resistance increases with degree of crystallinity. 

The diffusion coefficient required to account for penetration of about 500 A is of the order of 10 cm /sec. (for a 200 s. bake). For small molecules (such as the monomeric resist components) this is a quite reasonable number, either above or below 7 (cf. measurements on camphorquinone in polycarbonate 18), which are in the range of 10 — 10 above Tg and 10 — 10 below). Tg of PVA is 85C (29). The situation is less clear with polymer diffusion. PPSQ apparently does not have a distinct Tg (20), but remains assy up to its thermal decomposition temperature (this report is for high material). Wang, et al., ( ) obtained diffusion coefficients of 10 cmVsec for high Af poly(but methacrylate) in latex particles, at temperatures well above Tg. It is possible that the low Af, siloxanes used here diffuse at substantially higher rates. Thus the postulated diffusion is plausible albeit not assured. 

The layer of soft-ice adjacent to an interface may be melted or disoriented by adding LiCl. By this means Blank 2) has shown that the value of E/ of a monolayer of octadecanol to the passage of CO2 could be reduced from about 300 sec. cm. for pure water to only about 30 sec. cm. for 8M LiCl solution. Under the latter conditions we believe that the soft-ice is apparently almost completely melted. A small amount of methanol in the water penetrates and somewhat disrupts the film of octadecanol, and Ri again drops from 300 sec. cm. to about 30 sec. cm. i, though with further increase in the methanol concentration the resistance increases again to about 500 sec. cm., presumably due to the methanol molecules held in or near the surface increasing the viscosity of the soft-ice layer. These interpretations of the experimental data are not those proposed by Blank, and further studies with a viscous-traction surface-viscometer (1) should certainly be carried out to test this soft-ice theory. 

The elimination or estimation of the axial dispersion contribution presents a more difficult problem. Established correlations for the axial dispersion coefficient are notoriously unreliable for small particles at low Reynolds number(17,18) and it has recently been shown that dispersion in a column packed with porous particles may be much greater than for inert non-porous particles under similar hydrodynamic conditions(19>20). one method which has proved useful is to make measurements over a range of velocities and plot (cj2/2y ) (L/v) vs l/v2. It follows from eqn. 6 that in the low Reynolds number region where Dj. is essentially constant, such a plot should be linear with slope Dj, and intercept equal to the mass transfer resistance term. Representative data for several systems are shown plotted in this way in figure 2(21). CF4 and iC io molecules are too large to penetrate the 4A zeolite and the intercepts correspond only to the external film and macropore diffusion resistance which varies little with temperature. 

The above factors, however, limit hydrolysis far less than conversion of the soluble polymer to the solid state, and most resistant of all substrates are those in which molecules are in a highly oriented or crystalline state. Into these it is difficult even for small water molecules to penetrate. What chance, then, for the large enzymes ... 

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