Molecular weight empirical methods

Leach, B. S., Collawn, J. F. Jr. and Fish, W. W. 1980. Behavior of glycopolypeptides with empirical molecular weight estimation methods. 2. In random coils. Biochemistry 19, 5741-5747. 

The method preferred in our laboratory for determining the UWL permeability is based on the pH dependence of effective permeabilities of ionizable molecules [Eq. (7.52)]. Nonionizable molecules cannot be directly analyzed this way. However, an approximate method may be devised, based on the assumption that the UWL depends on the aqueous diffusivity of the molecule, and furthermore, that the diffusivity depends on the molecular weight of the molecule. The thickness of the unstirred water layer can be determined from ionizable molecules, and applied to nonionizable substances, using the (symmetric) relationship Pu = Daq/ 2/iaq. Fortunately, empirical methods for estimating values of Daq exist. From the Stokes-Einstein equation, applied to spherical molecules, diffusivity is expected to depend on the inverse square root of the molecular weight. A plot of log Daq versus log MW should be linear, with a slope of —0.5. Figure 7.37 shows such a log-log plot for 55 molecules, with measured diffusivities taken from several... 

A fourth technique used for the characterization of molecules is mass spectrometry. It is included in this chapter because the structural information it provides is similar to that obtained from the other techniques although the principle is entirely different. It is a destructive method in which the fragmentation pattern of sample molecules is used to determine empirical formulae and molecular weights, and to identify structural features. 

Moreover it requires only simple apparatus. However, this method of determining Molecular weights is not an absolute method. To find the Molecular weight from the viscosity data, it is essential to use empirical equations that give viscosity as a function of the Molecular weight. These equations are set up with the aid of any suitable absolute method for the determination of the Molecular weights. 

Estimation is easier and less time-consuming because use is made of empirical relationships between the BCF and physicochemical properties of the compound, such as water solubility (S) [42-48], Km, (solid organic carbon/water partition coefficient) [48], Kmw (membrane water partition coefficient), iipw (liposome water partition coefficient) [49], critical micelle concentration (CMC) [45], steric factors, molecular weight [47,48], and others. The most common regression method is the estimation of BCF from the octanol-water partition coefficient (Kovl) [18,42,44-48,50,51],... 

In Hawkesbury, Mark found the state of the laboratory just as Thorne and Wang had described. The laboratory equipment was outdated, and the scientists were employing the older, conventional, empirical methods. Clearly, the laboratory was well behind in the principles and procedures advocated by the new schools of high molecular weight chemistry in Europe. Even Mark, who was very well known throughout Europe, required introduction. Yet, despite these problems, modernization of the laboratories was not difficult. Above it all, Mark was greeted by enthusiastic, inquisitive coworkers and sufficient capital to initiate the required changes. 

The molecular mechanics method is extremely parameter dependent. A force field equation that has been empirically parameterized for calculating peptides must be used for peptides it cannot be applied to nucleic acids without being re-parameterized for that particular class of molecules. Thankfully, most small organic molecules, with molecular weights less than 800, share similar properties. Therefore, a force field that has been parameterized for one class of drug molecules can usually be transferred to another class of drug molecules. In medicinal chemistry and quantum pharmacology, a number of force fields currently enjoy widespread use. The MM2/MM3/MMX force fields are currently widely used for small molecules, while AMBER and CHARMM are used for macromolecules such as peptides and nucleic acids. 

Using the methods of Chapter 10, we find the empirical formula to be C3H2C1. jf this were the true formula, the molecular weight would be 73.5. The freezing point depression gives a molecular weight of approximately 150. This is not an accurate value, for the experimental measurement is subject to some error, but it indicates that the true molecular weight is near 150. 

Our approach has been essentially empirical in nature with less emphasis on the theoretical. We have isolated single substances, proved their purity, and determined their covalent structure by classical methods of organic chemistry we have then used these substances of molecular weight ranging from 1,000 to 14,000 as model solutes for the study of conformation and intermolecular interaction. Solutes of special interest have been gramicidin SA (2), bacitracin A (3), polymyxin B, and the tyrocidines A, B, and C (4). All are cyclic antibiotic polypeptides. The first three behave in aqueous solution as reasonably ideal solutes and do not associate, but the tyrocidines associate strongly and are interesting models for the study of association phenomena. Other model solutes of... 

In the Introduction it has been mentioned that the immediate reason for the development of phase distribution chromatography was the search for a fast and exact method to determine very narrow molecular weight distributions of polystyrenes obtained from anionic polymerization. The long way to reach this goal became evident only in the course of the investigations shown in the previous sections and representing a basis for the computation of such MWDs. In fact, not only exact measurements are necessary, but also mathematical expressions for the measured calibration curves and for the spreading of the injected concentration profile in the column must be stated, which cannot be done empirically. 

The experimental temperature dependence is much more closely reproduced by the empirical correlations of Dawson et al. (43) and of Mathur and Thodos (44). The exact experimental values are not reproduced by any of the methods. However, considering the difference in molecular weight between toluene and tolu-ene-d0,the approximations involved,and the error in the experimental values (which gets higher as the density decreases), the correlation of Mathur and Thodos gives a very good estimation of the self diffusion coefficient in supercritical toluene. 

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