Cavity surface area

In this relationship. S is alkane solubility, A is the cavity surface area and a is the hydrophobic free energy per unit area. Extensive fitting of this equation [24] yields a value of 88 kJ mol A for the proportionality constant a. This value corresponds to an unfavourable free energy of about 3.6 kJ mol for the transfer of a CH2 group to aqueous solution. 

The PCM algorithm is as follows. First, the cavity siuface is determined from the van der Waals radii of the atoms. That fraction of each atom s van der Waals sphere which contributes to the cavity is then divided into a nmnber of small surface elements of calculable surface area. The simplest way to to this is to define a local polar coordinate frame at tlie centre of each atom s van der Waals sphere and to use fixed increments of AO and A(p to give rectangular surface elements (Figure 11.22). The surface can also be divided using tessellation methods [Paschual-Ahuir d al. 1987]. An initial value of the point charge for each surface element is then calculated from the electric field gradient due to the solute alone ... 

Attempts have been made to distinguish between these theories on the basis of the AH° and values anticipated for the two theories, but it may be illusory to think of them as independent alternatives. The eavity model has been criticized on the basis that it eannot account for certain observations such as the denaturing effect of urea, but it must be noted that the cavity theory includes not only the cavity term AAy, but also a term (or terms) for the interaction of the solutes and the solvent. A more eogent objeetion might be to the extension of the macroseopic concepts of surface area and tension to the molecular scale. A demonstration of the validity of the cavity concept has been made with silanized glass beads, which aggregate in polar solvents and disperse in nonpolar solvents. 

In the models discussed thus far in this section, emphasis has been placed on electrostatic effects and solvent polarity. An alternative view that to some extent takes other forces into account begins with the idea that, in order to dissolve a solute molecule in a solvent, energy is required to create a cavity in the solvent the solute is then inserted into this cavity. In Section 8.2 we saw that the energy to create a cavity can be expressed as a product of the surface area of the cavity and the surface tension of the solvent. An equivalent expression is obtained as the product of the volume of the cavity and the pressure exerted by the solvent, and we now explore this concept. 

The Polarizable Continuum Model (PCM) employs a van der Waals surface type cavity, a detailed description of the electrostatic potential, and parameterizes the cavity/ dispersion contributions based on the surface area. The COnductor-like Screening... 

The combinatorial term Pcomb(X,S) in Eq. (11) denotes a usually small correction for size and somewhat also for shape dilferences of the solutes and solvents, which is reasonably well understood from chemical engineering models. It is an empirical function, depending only on the surface areas and volumes of solute and solvent molecules, which are reasonably known from the COSMO cavities. The error arising from the approximations made in the combinatorial term can be expected to be much less than IkJ mol, or 0.17 log units, and hence can be safely neglected in the context of drug solubiUty estimation. 

Where AG is the free energy term associated with cavity formation, N is Avogadro s number, AA is the change in surface area due to... 

AGg (X) can be removed by assuming that it is equivalent to the polar contribution to the free energy of solution of solute X in a nonpolar hydrocarbon solvent, such as squalane. A second reason for using a reference hydrocarbon solvent is to correct, at least partially, for the fact that the hardcore van der Haals volume is a poor estimate of the size of the cavity and its accessible surface for solvent interactions for aromatic and cyclic solutes. The solvent accessible surface area would logically be the preferred parameter for the cavity term but is very difficult to calculate while the van der Haals volume is readily accessible. With the above approximations the solvent interaction term for... 

Peritoneal dialysis (PD) utilizes similar principles as hemodialysis in that blood is exposed to a semipermeable membrane against which a physiologic solution is placed. In the case of PD, however, the semipermeable membrane is the peritoneal membrane, and a sterile dialysate is instilled into the peritoneal cavity. The peritoneal membrane is composed of a continuous single layer of mesothelial cells that covers the abdominal and pelvic walls on one side of the peritoneal cavity, and the visceral organs, including the GI tract, liver, spleen, and diaphragm on the other side. The mesothelial cells are covered by microvilli that increase the surface area of the peritoneal membrane to approximate body surface area (1 to 2 m2). 

Under normal circumstances, the skeleton undergoes a dynamic process of bone remodeling. Bone tissue responds to stress and injury through continuous replacement and repair. This process is completed by the basic multicellular unit, which includes both osteoblasts and osteoclasts. Osteoclasts are involved with resorption or breakdown of bone and continuously create microscopic cavities in bone tissue. Osteoblasts are involved in bone formation and continuously mineralize new bone in the cavities created by osteoclasts. Until peak bone mass is achieved between the ages of 25 and 35, bone formation exceeds bone resorption for an overall increase in bone mass. Trabecular bone is more susceptible to bone remodeling in part owing to its larger surface area. 

Intraperitoneal (IP) Into the peritoneal cavity of the abdomen this provides a large surface area for absorption and is widely used for administering drugs to laboratory animals. It is very rarely used clinically. 

In (2.105), the assumption of the proportionality of solvent-accessible surface and cavity energy is explicitly shown, and therefore ak depends on the type of the k-atom interacting with the solvent. Ak(p ) is the complex function describing the solvent accessible surface area, and depends on p, which is defined by the following expression ... 

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