Molecular critical packing parameter

The molecular descriptors refer to the molecular size and shape, to the size and shape of hydrophilic and hydrophobic regions, and to the balance between them. Hydrogen bonding, amphiphilic moments, critical packing parameters are other useful descriptors. The VolSurf descriptors have been presented and explained in detail elsewhere [8]. The VolSurf descriptors encode physico-chemical properties and, therefore, allow both for a design in the physico-chemical property space in order to rationally modulate pharmacokinetic properties, and for establishing quantitative structure-property relationships (QSPR). 

Critical packing parameter (CP) is the ratio between the hydrophobic and lipophilic parts of a molecule. In contrast to HL balance, CP refers just to the molecular shape. 

Molecular dynamics simulations are consistent with calculations based on the critical packing parameter p, which indicate that the structure of the surfactant controls the shape of the micelle at the cmc. Esselink et al. [16] show that the surfactants / 2/5, hihts, and h thts form bilayers, cylindrical micelles, and spherical micelles, respectively, as expected. However, /14/4, expected to form micelles of low curvature based on p, instead forms sphere-like structures due to the coiling of the headgroup. If this increased effective headgroup area is accounted for in the calculation of the packing parameter, then a spherical shape is predicted, in agreement with the result of the simulations. 

A simple but effective concept described by Israelachvilli et al. predicts the aggregation of surfactants in solution. This model is based on the molecular shape of the surfactant molecules. In this model, the ratio of the size of the hydrophobic and the hydrophilic portion of the molecules is expressed in terms of a critical packing parameter P [9] ... 

Critical packing parameter Approximate molecular shape Expected aggregate structure... 

FIGURE 15.11. The critical packing parameter, allows one to quickly determine the general type of aggregate structure to be expected for a given surfactant molecular composition. 

Surfactant-like lipids adopt either normal (type 1) or inverted (type 2) self-assembled phases, resulting in either oil-in-water (o/w) phases with convex curvature lipid/water interface or water-in-oil (w/o) phases with a concave interface, respectively. The formation of a normal or an inverted self-assembled nanostructure in water mainly depends on the lipid s molecular shape, as discussed in the seventies by Israelachvili and co-workers [78], In this regard, the geometric shape of the lipid can be a useful tool for predicting the water-lipid interface curvature and also can be helpful in imderstanding the phase behavior of binary, ternary, and even multi-component systems [79], For this purpose, the shape factor or more commonly known in the literature as the critical packing parameter CPP) was defined [78] as ... 

FIGURE 16.1 Surfactant molecules self-assemble into various aggregate shapes, depending on the surfactant molecular structure as described by the critical packing parameter (CPP), which is the ratio of the molecular volume (v) divided by its length (/) times the cross-sectional area of the head group (a) v/al. 

In developing controlled-release matrices, the solubilization capacity of miaoanulsions should be optimized, which depends on various factors, such as the oitical micelle concentration, the surfactant s HLB value, the critical packing parameter and molecular compatibility between the oil, surfactant and co-surfactant (Friberg et al., 1994 Aboofazeli et al., 1995 von Corswant and Soderman, 1998). 

The comparison of the results on enhanced thermal stability of proteins in LB films reported here and those already published again underlines that molecular close packing is a critical parameter responsible for this phenomenon. 

Lipophilic and hydrophilic calculations are performed at -0.6 and -3.0kcalmol", respectively. Critical packing is a good parameter to predict molecular packing such as in micelle formation, and may be relevant in solubility studies in which the melting point plays an important role. 

The hydrophobic effect , firstly recognized by Tanford, is responsible of selfassociation phenomena. Amphiphilic molecules can form micellar systems provided that their packing parameter, vjal, is not too close to unity. Significant changes of NMR parameters are observed as a result of amphiphiles self-assembly. Indeed molecules experience strong intermolecular interactions due to the interplay of both electrostatic and van der Waals forces. Micellar aggregates usually form isotropic liquid systems, thus NMR experiments can be easily performed and modeled. Hence chemical shifts, relaxation, and self-diffusion NMR measurements can provide reliable information, at a molecular level, on critical micelle concentration (c.m.c.), molecular conformations and interactions, counterion binding, hydration also in mixtures of different amphiphiles. 

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