Physicochemical membrane

One decade has passed since the parallel artificial membrane permeation assay (PAM PA) was first introduced in 1998 [47]. Since then, PAM PA rapidly gained wide popularity in drug discovery [3, 48-51]. Today, PAMPA is the most widely used physicochemical membrane permeation model. The term PAMPA is nowusedas the general name for a plate-based (HTS enabled), biter-supported (filter immobilized) artificial membrane. Typically, phospholipids dissolved in an organic solvent are impregnated into the filter to construct a PAMPA membrane. 

Fresen, K. O., and Ubendorfer, A., 1973, Physicochemical membrane changes in Ehrlich ascites tumor cells infected with oncolytic influenza virus, Arch. Gesamte Virus-forsch. 41 267. 

In subsequent studies attempting to find a correlation of physicochemical properties and antimicrobial activity, other parameters have been employed, such as Hammett O values, electronic distribution calculated by molecular orbital methods, spectral characteristics, and hydrophobicity constants. No new insight on the role of physiochemical properties of the sulfonamides has resulted. Acid dissociation appears to play a predominant role, since it affects aqueous solubiUty, partition coefficient and transport across membranes, protein binding, tubular secretion, and reabsorption in the kidneys. An exhaustive discussion of these studies has been provided (10). 

Diffusion. Diffusional dmg delivery systems utilize the physicochemical energy resulting from concentration differentials. Dmg molecules diffuse through a polymer matrix or through a polymer membrane film from a region of high concentration to one of low concentration. 

Membrane Pervaporation Since 1987, membrane pei vapora-tion has become widely accepted in the CPI as an effective means of separation and recovery of liquid-phase process streams. It is most commonly used to dehydrate hquid hydrocarbons to yield a high-purity ethanol, isopropanol, and ethylene glycol product. The method basically consists of a selec tively-permeable membrane layer separating a liquid feed stream and a gas phase permeate stream as shown in Fig. 25-19. The permeation rate and selectivity is governed bv the physicochemical composition of the membrane. Pei vaporation differs From reverse osmosis systems in that the permeate rate is not a function of osmotic pressure, since the permeate is maintained at saturation pressure (Ref. 24). 

A chemical must have certain physicochemical properties to elicit an endocrine disrupting effect. For example, the ability to enter the body and to cross the cell membrane into the cellular medium requires a degree of lipophilicity. Fipophilic potentials may be compared by reference to the chemical s octanol-water coefficient (usually expressed as log K ). This property, together with molecular size and chemical structure, has an important influence on the bioacciimiilation... 

Due to their physicochemical properties trace amines can pass the cell membrane to a limited extent by passive diffusion, with the more lipophilic PEA and TRP crossing membranes more readily than the more polar amines TYR. and OCT. In spite of these features, trace amines show a heterogeneous tissue distribution in the vertebrate brain, and for TYR. and OCT storage in synaptic vesicles as well as activity-dependent release have been demonstrated. So far, trace amines have always been found co-localized with monoamine neurotransmitters, and there is no evidence for neurons or synapses exclusively containing trace amines. 

Liposomes have been widely used as model membranes and their physicochemical properties have therefore been studied extensively. More recently, they have become important tools for the study of membrane-mediated processes (e.g., membrane fusion), catalysis of reactions occurring at interfaces, and energy conversion. Besides, liposomes are currently under investigation as carrier systems for drugs and as antigen-presenting systems to be used as vaccines. 

The SUM was covered by a polymer film with an orifice of approximately 0.3 mm in diameter on each side, and subsequently a folded BLM was generated from a DPhPC/l,2-dipalmitoyl-in-glycero-3-phosphatidic acid (DPPA) monolayer on the side facing the SUM (Fig. 19). Interestingly, no pretreating of the orifice with any alkane or lipid was required, as is imperative for all other BLM techniques. Thus, an accumulation of such compounds could be excluded, and the physicochemical properties of the membrane and... 

A close relationship exists between physicochemical properties of pigment molecules and their ability to be absorbed and thus to exhibit biological functions. Carotenoids are hydrophobic molecules that require a lipophilic environment. In vivo, they are found in precise locations and orientations within biological membranes. For example, the dihydroxycarotenoids such as lutein and zeaxanthin orient themselves perpendicularly to the membrane surface as molecular rivets in order to expose their hydroxyl groups to a more polar environment. 

Conversely, in a membrane model, acetylcholine showed mean log P values very similar to those exhibited in water. This was due to the compound remaining in the vicinity of the polar phospholipid heads, but the disappearance of extended forms decreased the average log P value somewhat. This suggests that an anisotropic environment can heavily modify the conformational profile of a solute, thus selecting the conformational clusters more suitable for optimal interactions. In other words, isotropic media select the conformers, whereas anisotropic media select the conformational clusters. The difference in conformational behavior in isotropic versus anisotropic environments can be explained considering that the physicochemical effects induced by an isotropic medium are homogeneously uniform around the solute so that all conformers are equally influenced by them. In contrast, the physicochemical effects induced by an anisotropic medium are not homogeneously distributed and only some conformational clusters can adapt to them. 

Loidl-Stahlhofen, A., Eckert, A., Hartmann, T Schottner, M. Solid-supported lipid membranes as a tool for determination of membrane affinity high-throughput screening of a physicochemical parameter. J. Pharm. Sci. 2001, 90, 599-606. 

Kansy, M., Senner, F., Gubemator, K. Physicochemical high throughput screening parallel artificial membrane permeation assay in the description of passive absorption processes. /. Med. Chem. 1998, 43, 1007-1010. 

The scope of this review is to summarize the recent development of the solution NMR to DD from aqueous phase to lipid bilayer membranes on the basis of our recent NMR work. Relevant physicochemical and computational aspects of the membrane DD are also referred to here. 

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