Molecular bulk

Taxonomically close to the Annonaceae, the Lauraceae family abounds with apor-phinoid alkaloids. A remarkable advance in the search for topoisomerase inhibitors from Lauraceae has been provided by Woo et al. (6). Using DNA-unwinding assay and structural modeling, they showed that dicentrine can attain a relatively planar conformation and molecular bulk which allow it to occupy the active site of topoisomerase II which becomes inactive. The requirement of a suboptimal conformation to achieve DNA binding appears to make dicentrine less potent against topoisomerase II than the... 

The lack of clear-cut hallucinogen-type activity for the 2-aminotetralins could be explained in several ways. The known deleterious effect of molecular bulk in the alpha-position would seem to direct attention to the steric effect of the reduced ring of the tetralins as detrimental to activity. In 18b, however, it has been noted (156) that the 5-methoxy group is forced out of plane by the adjacent 6-methyl and 4-methylene groups. The importance to activity of maintaining the methoxy groups coplanar with the aromatic ring has been emphasized earlier. Both substituent orientation and N-alkylation must also be important to activity, and it may not be realistic to make direct comparisons between the phenethyl-amines and the 2-aminotetralins. 

MolES E-state descriptor representing the molecular bulk... 

Another classical measure of the molecular geometry of substituents is the Verloop steric parameter. This is calculated from bond angles and atomic dimensions— primarily the lengths of substituent groups and several measures of their width. Trivial as this may sound, the consideration of molecular bulk is an important and often neglected factor in making multiple quantitative correlations of structure and pharmacological activity. Balaban et al. (1980) devised several related methods that are still in use today. 

Using PCA, Cramer found that more than 95% of the variances in six physical properties (activity coefficient, partition coefficient, boiling point, molar refractivity, molar volume, and molar vaporization enthalpy) of 114 pure liquids can be explained in terms of only two parameters which are characteristic of the solvent molecule (Cramer 111, 1980). These two factors are correlated to the molecular bulk and cohesiveness of the individual solvent molecules, the interaction of which depends mainly upon nonspecific, weak intermolecular forces. 

The molecular volume Vt of each species (considered impenetrable) may be estimated from empirical Van der Waals radii or other theoretical measures of molecular bulk, and all species are considered to have access to the same free volume in the numerator. However, Vexcl is often neglected entirely for gaseous reactions at low density, and approximations to trans are generally found to have little effect on overall AGrxn or KQq. 

Molecular bulk diffusion coefficient Effective diffusivity... 

Values of a can be determined to 0.01, varying between 0 and 3.5, and reflect the affinity of the functional group of the solvent to the phenyl ring on the one hand and the steric hindrance due to the molecular bulk of the solvent on the other. It was also shown (Errede 1989) that the Flory-Huggins interaction parameter % at solvent volume fractions cp in the solvent-copolymer system is given by ... 

The examples underline the importance of molecular bulk and mainly the hydrogen bond accepting strength for the interaction of chemicals and drugs with phospholipids. 

Certain precautions need to be observed at the outset of this effort. To be an appropriate subject for downsizing, an antibody must achieve critical interactions with at least part of the receptor-binding surface of IL-ip. This is to exclude selection of an antibody that blocks access of IL-1 p to the receptor merely by steric overlap of its molecular bulk with the space occupied by bound receptor (5). Such an antibody, on downsizing, would lead to a compound that fails to compete with IL-ip binding. Here we describe the selection and characterization of an antibody, and its Fab fragment, that provides a suitable starting point for this endeavor. 

Wells et al. investigated 16 C1-C5 n-alkylbenza-mides by RP-HPLC on a Partisil ODS column using methanol and water, as well as acetonitrile and water, in different volume compositions as mobile phases. Log Id and log k values were correlated with topological indices Xt and Xt values. The highest correlations were obtained with connectivity data that describe molecular bulk, branching in the hydrocarbon portion of the molecule. For example, for log values for 0% acetonitrile in mobile phase on Partisil ODS-2 and Ultrasphere ODS, the following correlation equations were obtained ... 

Isobaric applications in the continuum regime, making use of molecular bulk diffusion and/or some viscous flow are found in catalytic membrane reactors. The membrane is used here as an intermediating wall or as a system of microreactors [29,46]. For this reason some attention will be paid to the general description of mass transport, which will also be used in Sections 9.4 and 9.5. 

Figure 20.1 Possible mechanisms of electronic excitations at molecular/bulk interfaces.

The —> physico-chemical properties used to derive BC(DEF) descriptors are activity coefficient in water, —> octanol-water partition coefficient, hoiling point, —> molarr activity, liquid state molar volume, and heat of vaporization. The eigenvalues and corresponding cumulative explained variances of the five principal properties (denoted by B, C, D, E, and F) are reported in Table B1. It can be noted that the first two principal properties B and C already explain 95.7% of the original variance of the six physico-chemical properties further analysis using different compounds and properties showed B and C to be independent of the data set used in their derivation, identifying them as measures of molecular bulk and cohesiveness, respectively. The other three parameters, D, E, and F, are of minor importance, however they were... 

Over the last decades, there has been an increasing interest in theoretical (1,2) and experimental (3) studies of weakly interacting complexes, the so-called van der Waals molecules. One of the reasons for this interest is that the spectra of these complexes depend very sensitively on the intermolecular potentials and other properties, such as interaction-induced dipole moments and polarizabilities, the knowledge of which is crucial for understanding the behavior of molecular bulk species. 

Yang, R, Shtein, M., and Forrest, S.R., Controlled growth of a molecular bulk heterojunction photovoltaic cell, Nat. Mater. 4, 37 1, 2005. 

The steiic attributes of a molecule include its size and shape. Molecular size or bulk is easily assessed from properties such as molecular weight, volume, or surface area. A summary of parameters for molecular bulk is provided by Livingstone (2000). Molecular shape is much more difficult to parameterize, and there is no single descriptor capable of doing so (Patel and Cronin, 2001b). Different aspects of molecular shape, such as chirality, linearity, and branching, are often addressed individually (Livingstone, 2003). 

---