Question 13 of 13: Identifying the Four Monomers of a Poly(ester amide) Drug-Delivery Copolymer

Question 13: Identifying the Four Monomers of a Poly(ester amide) Drug-Delivery Copolymer

Question text not reproduced: the examination questions are © Engineers and Geoscientists BC. Open the official past paper (linked at the top of this page) to read the question, then follow the worked solution below.

[Figure not reproduced: poly(ester amide) A — one repeat unit, redrawn from the source structure. See the official exam paper.]

Approach. Walk the backbone bond-by-bond and classify every linkage as an amide (C(=O)–N) or an ester (C(=O)–O), then group the atoms between consecutive amide/ester bonds into the monomer that must have supplied them.

1. A four-carbon diacid links two different amine-bearing fragments. Reading from the left, –C(=O)CH₂CH₂C(=O)– is flanked by amide bonds on both sides (this exact fragment recurs twice in the repeat unit) — this is succinic acid, HOOC–CH₂CH₂–COOH, condensed twice as a simple diacid monomer (no stereocentre, not an amino acid).
   succinic acid
2. An isobutyl-bearing amino-acid residue is esterified on both sides to a two-carbon diol. The next fragment, –NH–CH(CH₂CH(CH₃)₂)–C(=O)–O–CH₂CH₂–O–C(=O)–CH(CH₂CH(CH₃)₂)–NH–, is symmetric: two identical α-amino-acid residues, each bearing the isobutyl side chain –CH₂CH(CH₃)₂ diagnostic of leucine, each contributing its free α-amine to an amide bond (to the succinic acid on either side) and its α-carboxyl to an ester bond with a common central diol — ethylene glycol, HO–CH₂CH₂–OH.
   leucine

   ethylene glycol
3. A four-methylene chain links directly into a benzyl-ester-capped stereocentre — both belong to a single lysine residue. The final segment, –NH–CH₂CH₂CH₂CH₂–CH(NH–)–C(=O)–O–CH₂C₆H₅, is one monomer, not two: the (CH₂)₄ chain is not a separate diamine — it terminates directly in the same stereocentre that carries the benzyl ester, which is exactly the connectivity of lysine used "in reverse": its side-chain (ε-) amine forms the amide bond back to the preceding succinic acid unit, its α-amine continues the backbone forward to the next repeat unit (via the amide bond at the chain's far right), and its α-carboxyl is capped as a permanent benzyl ester — a protecting/pendant group rather than a backbone linkage. This is the monomer actually used industrially as "lysine benzyl ester" in real AABB-type poly(ester amide) biomaterials, precisely because both of lysine's amines are then free to build the backbone while the carboxyl is safely capped, preventing unwanted branching/crosslinking.
   lysine benzyl ester

The two amino acids are leucine and lysine.