Molecular design lipophilicity

Gaillard, P., Carrupt, P.A., Testa, B. and Boudon, A. (1994) Molecular lipophilicity potential, a tool in 3D-QSAR. Method and applications. Journal of Computer-Aided Molecular Design, 8, 83-96. 

Mannhold, R., Cruciani, G., Dross, K. and Rekker, R. (1998) Multivariate analysis of experimental and computational descriptors of molecular lipophilicity. Journal of Computer-Aided Molecular Design, 12, 573-581. 

FIG. 11 Schematic view of the designed photocatalytic systems with (a) transmembrane and (b) interfacial electron transfer, which is photosensitized by the CdS nanoparticles attached to the lipid membrane surface. Menaquinone (MQ) and heteropolyanions (HPA, SiWi20jo) are lipophilic molecular electron relays. Palladium particles are attached to CdS and operate as dark catalysts of hydrogen evolution from water. MV + methylviologen bication Gl glucose. 

The initial motivation for the use of SAR was to empirically define and quantify the effects of steric, electronic, and lipophilic properties of substituents on biological activity. Not surprisingly, the retrospective success of early studies in predicting bioactivity attracted industrial attention, taking Computer-Aided Molecular Design (CAMD) out of the academic realm and into the pharmaceutical, agricultural, and polymer chemistry companies. 

Lewis, M.L. and Cucurull-Sanchez, L. (2009) Structural pairwise comparisons of HLM stability of phenyl derivatives introduction of the Pfizer metabolism index (PMI) and metabolism-lipophilicity efficiency (MLE). Journal of Computer-Aided Molecular Design, 23 (2), 97-103. 

Mortenson, PJSI. and Murray, C.W. (2011) Assessing the lipophilicity of fragments and early hits. Journal of Computer-Aided Molecular Design, 25,663-667. 

After many trials in the molecular design of chiral crown ethers, a 1,1 -binaphthyl unit incorporated in a macroring by substitution in the 2,2 -positions proves to possess the desirable properties. The naphthalene-containing system, chosen for practical and strategic reasons, imparts rigidity and lipophilicity to conventional cyclic polyethers. The synthesis of such a host is presented in Fig. 5.2. 

Some of their derivatives have been used as antiviral drugs. Due to their flexible chemistry, they can be exploited to design drug delivery systems and in molecular nanotechnology. In such systems, they can act as a central lipophilic core and different parts like targeting segments, linkers, spacers, or therapeutic agents can be attached to the said central nucleus. Their central core can be functionalized by peptidic and nucleic acid sequences and also by numerous important biomolecules. 

Efremov R.G. Chugunov A.O. Pyrkov T.V. Priestle J.P. Arseniev A.S. Jacoby E. Molecular lipophilicity in protein modeling and drug design. Current Medicinal Chemistry, 2007, 14, 393—415. 

The considerable interest in the design of container molecules [26, 27, 30], for their potential application as nano-scale chemical reactors has particularly received much attention [97]. In this sense, supramolecular catalysis allowing the chemical transformation of a substrate selectively entrapped within a molecular receptor, will behave as a chemical reactor [98]. One way to obtain a supramolecular catalysis, is to design a molecular receptor containing a lipophilic cavity allowing selective substrate binding, and specific sites for metal ion coordination [97, 99]. Attempts in this direction have... 

Heiden, W., Moeckel, G., and Brickmann, J. (1993) A new approach to analysis and display of local lipophilicity/hydrophilicity mapped on molecular surfaces.. /. Comput.-Aided Mol. Design 7, 503-514. 

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