The design of polymers for specialty applications such as medical implants, 1,2 piezoelectric 3 and photonic materials, 4 or self-assembling systems 5 is challenging since such materials must meet multifaceted requirements. For example, the field of tissue engineering hinges on developing degradable scaffolds that promote cell proliferation and expression of desired physiologic behaviors through careful control of the polymer surface properties. 6 Here we report the concept of permutationally designed monomer systems to create libraries of structurally related polymers. To obtain libraries in which material properties vary in a predictable and systematic fashion, it is necessary to use carefully designed monomers and polymerization strategies. This can be achieved in strictly alternating A-B type copolymers in which the first monomer (A) contains a reactive group for the attachment of a series of pendent chains, while the second monomer (B) allows for systematic variations in the polymer backbone structure. The copolymerization of n different monomers A with m different monomers B gives rise to an array of n×m structurally related copolymers. Such libraries can be used to (1) increase the number of available polymeric candidate materials for any specific application and (2) systematize the study of correlations between polymer structure, material properties, and performance. As a first implementation of this concept, a library of 112 polyarylates 3 was prepared from 14 distinct tyrosine-derived diphenols 1 and eight aliphatic diacids 2 ( Figure 1). These polymers are based on natural metabolites and are biodegradable and potentially useful as medical implant materials. 7 In the set of tyrosine-derived diphenols 1, the pendent group R and the number of methylene groups (n ) 0, 1) were varied, while in the set of diacids 2, the polymer backbone was varied via structural changes at Y. In combination, variations at R and Y provided incremental differences in polymer free volume, bulkiness, flexibility, and hydrophobicity. We found that the library of 112 polymers exhibited predictable changes in glass transition temperature (T g ), surface wettability (as measured by the air-water contact angle), and cellular response (as measured by in vitro cell proliferation studies). On the other hand, since all polymers were derived from very similar monomers, they could be prepared under identical reaction conditions and shared important material properties such as solubility in organic solvents, thermal processibility, and amorphous morphology.Up to 32 simultaneous reactions on a 0.2 g scale (based on the amount of diphenol 1) were conducted in separate reaction vessels set up in a water shaker bath. Since the monomers used had almost identical reactivities at their respective functional groups, the same reaction conditions were employed and each polymerization was conducted and worked up in the same reaction vessel. About 0.1-0.2 g of each polymer was obtained after two precipitations from methanol. This methodology can be...