Progress toward the synthesis of a biomimetic membrane Kyle W. Gano and David C. Myles* Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095-1569, USA Received 24 March 2000; revised 7 April 2000; accepted 9 April 2000 Abstract Ubiquinone has antioxidant properties and is important in the conversion of products from glycolysis and the citric acid cycle to ATP. We report the synthesis of the necessary components of a biological membrane mimic that can serve as a model system for elucidating the third step in the prokaryotic bio- synthesis of ubiquinone. # 2000 Elsevier Science Ltd. All rights reserved. The electron-transport chain converts the products of glycolysis and the citric acid cycle into energy in the form of ATP. A key component in this process is ubiquinone (coenzyme Q or Q). y Existing as a nonpolar molecule that diuses freely within the extensive mitochondrial frame- work, ubiquinone is an essential lipid component of the mitochondrial electron-transport chain of eukaryotes and the plasma membrane of many prokaryotes. 1 Q is also present in other intra- cellular membranes and human low-density lipoproteins. 2 It has been shown that the reduced form of Q (QH 2 ), the hydroquinone, functions as an antioxidant by scavenging lipid peroxy radicals, a class of oxidative products that represents a major cause of damage to cellular membranes. Oxidative damage to mammalian cells has been linked to cancer and age-related degenerative diseases. 3 Despite the importance of Q/QH 2 , many aspects of Q biosynthesis are still incomplete. Our approach to investigate the biosynthesis of ubiquinone, specifically the step catalyzed by an O-methyltransferase 4 in the presence of S-adenosylmethionine, is to use self-assembled monolayers (SAMs) to model the inner-mitochondrial membrane (Fig. 1). We report here the synthesis of the key components of this biological membrane: an alkanethiol phosphonic acid, which mimics the phosopholipid component, 5 and an alkenethiol ubiquinone precursor tether. The mixed monolayer assembly on gold provides an excellent scaold to probe the prokaryotic enzyme-binding site in the third step of ubiquinone biosynthesis. 0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved. PII: S0040-4039(00)00597-9 Tetrahedron Letters 41 (2000) 4247–4250 * Corresponding author. Associate Director Organic and Medicinal Chemistry, Chiron Corporation, 5300 Chiron Way, Mail Stop 4.5, Emeryville, CA 94608-2916, USA. E-mail: david_myles@cc.chiron.com y Abbreviations: Q, ubiquinone; QH2, ubiquinol.