Macromolecular effects

Reitz RH, Quast JF, Scott WT, et al. 1980. Pharmacokinetics and macromolecular effects of chloroform in rats and mice. Implications for carcinogenic risk estimation. Water chlorination environmental impact and health effects 3 983-993. 

Etoposide is a podophyllotoxin derivative. Its main effect appears to be at the G2 portion of the cell cycle. At high concentrations (10 mcg/mL or more), lysis of cells entering mitosis is seen at low concentrations (0.3 to 10 meg/ mL), cells are inhibited from entering prophase. Predominant macromolecular effect appears to be DNA synthesis inhibition. Etoposide is indicated in refractory testicular tumors, and smaU-ceU lung cancer. 

In Fig. 1, auto-mono-ADP-ribosylation of the enzyme was assayed at a constant substrate concentration of 25 nM NAD+ as ADP-ribose donor (1). It should be noted that relatively small apparent differences in the saturation ciuves of the octamers actually correspond to significant differences because of the logarithmic abscissa. At or below an octamer/enzyme ratio of 1 1, duplex C was the most effective coenzyme, while (dA dT)8 was the poorest. The effect of sDNA on mono(ADP-ribosyl)ation was biphasic. Below an sDNA/enzyme ratio of 0.004 1 (first arrow) sDNA was hardly effective, whereas increasing the sDNA/enzyme ratio to 0.04 1 (second arrow), the coenzymatic effect of sDNA was maximal. A stmctural contribution of the much larger sDNA species, as compared to the synthetic octamers, apparently introduces macromolecular effects of sDNA on the enzyme which cannot occur with small oligo-DNAs. 

Two useful review articles on the theory of the kinetics and statistics of reactions of functional groups on polymers have appeared. Both polymer-analogous and intramolecular transformation reactions are influenced by a number of specifically macromolecular effects. These include neighbouring-group effects, configurational and conformational effects, electrostatic and supermolecular effects. The incorporation of all these factors into a general theory of macromolecular reactions is extremely difficult. These reviews provide introductions to the mathematical models as well as state-of-the-art overviews. 

Each of these special macromolecular effects will now be illustrated. 

Up to now, for stereoregular copolymers, non-linear variation has been considered as resulting from conformational effect as in the case of copolymers of chiral and achiral units [59, 60]. As shown above, for polymers with very low probabilities for regular secondary structures in solution, no macromolecular effects can be reasonably taken into account and another origin must be suggested. 

It is difficult to precisely define the change induced by the transition from the simple molecular level to the macromolecular one. Depending upon the property considered, the macromolecular effect will be indeed perceptible at a lower or higher threshold of molar mass for example, the majority of industrially produced linear polymers used in daily life are in the range of 10 g-mol ... 

C. R. Bennet, R. S. Ring, and P. J. Petersen, Pressure Effects on Macromolecular—Water Interactions with Synthetic Membranes, ACS 181st National Meeting, Atlanta, Ga., Mar. 1981. 

An understanding of a wide variety of phenomena concerning conformational stabilities and molecule-molecule association (protein-protein, protein-ligand, and protein-nucleic acid) requires consideration of solvation effects. In particular, a quantitative assessment of the relative contribution of hydrophobic and electrostatic interactions in macromolecular recognition is a problem of central importance in biology. 

It is possible to go beyond the SASA/PB approximation and develop better approximations to current implicit solvent representations with sophisticated statistical mechanical models based on distribution functions or integral equations (see Section V.A). An alternative intermediate approach consists in including a small number of explicit solvent molecules near the solute while the influence of the remain bulk solvent molecules is taken into account implicitly (see Section V.B). On the other hand, in some cases it is necessary to use a treatment that is markedly simpler than SASA/PB to carry out extensive conformational searches. In such situations, it possible to use empirical models that describe the entire solvation free energy on the basis of the SASA (see Section V.C). An even simpler class of approximations consists in using infonnation-based potentials constructed to mimic and reproduce the statistical trends observed in macromolecular structures (see Section V.D). Although the microscopic basis of these approximations is not yet formally linked to a statistical mechanical formulation of implicit solvent, full SASA models and empirical information-based potentials may be very effective for particular problems. 

By covalently attaching reactive groups to a polyelectrolyte main chain the uncertainty as to the location of the associated reactive groups can be eliminated. The location at which the reactive groups experience the macromolecular environment critically controls the reaction rate. If a reactive group is covalently bonded to a macromolecular surface, its reactivity would be markedly influenced by interfacial effects at the boundary between the polymer skeleton and the water phase. Those effects may vary with such factors as local electrostatic potential, local polarity, local hydrophobicity, and local viscosity. The values of these local parameters should be different from those in the bulk phase. 

On the basis of the above data it has been hypothesized that the conductivity of PFCM is due not to the contact between the filler particles but the current passes across the thin (less than 1 -2 microns) polymer interlayers. The conductivity arises when a spontaneous pressure exceeding the threshold value develops in the material. The overstresses apparently arise as a result of PP crystallization in the very narrow gaps between the filler particles [312], Since crystallization must strongly affect the macromolecular conformation whereas the narrowness of the gap and fixed position of molecules on the filler prevent it, the heat released in the process of crystallization must, in part, be spent to overcome this hindrance, whereby a local high pressure may arise in the gap. This effect is possible only where there are gaps of the size comparable with that of macromolecules. The small gap thickness will also hamper pressure relaxation, since the rate of flow from such a narrow clearance should be negligibly small. 

From the various autocorrelation times which characterized macromolecular fluctuations, those associated with the fluctuation of the electrostatic field from the protein on its reacting fragments are probably the most important (see Ref. 8). These autocorrelation times define the dielectric relaxation times for different protein sites and can be used to estimate dynamical effects on biological reactions (see Chapter 9 for more details). 

The effect of media viscosity on polymerization rates and polymer properties is well known. Analysis of kinetic rate data generally is constrained to propagation rate constant invarient of media viscosity. The current research developes an experimental design that allows for the evaluation of viscosity dependence on uncoupled rate constants including initiation, propagation and macromolecular association. The system styrene, toluene n-butyllithium is utilized. 

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