Ionizable lipids and methods of manufacture and use thereof

A compound of Formula III:

• wherein each of R1, R2, R11, and R12 is independently selected from the group consisting of H, optionally substituted C1-C12 alkyl, optionally substituted C2-C12 alkenyl, optionally substituted C2-C12 alkynyl, optionally substituted C3-C6 cycloalkyl, optionally substituted C4-C6 heterocycloalkyl, optionally substituted C4-C6 alkylcycloalkyl, optionally substituted C4-C6 aryl, optionally substituted C3-C6 heteroaryl, optionally substituted C4-C8 aryloxy, optionally substituted C7-C10 arylalkyl;
• optionally substituted C5-C10 heteroarylalkyl group, and optionally substituted amine;
• wherein R1′ is selected from the group consisting of H, C1-C12 alkyl, optionally substituted C2-C12 alkenyl, optionally substituted C2-C12 alkynyl, optionally substituted C3-C6 cycloalkyl, optionally substituted C4-C6 heterocycloalkyl, optionally substituted C4-C6 alkylcycloalkyl, optionally substituted C4-C6 aryl, optionally substituted C3-C6 heteroaryl, optionally substituted C4-C8 aryloxy, optionally substituted C7-C10 arylalkyl;
• optionally substituted C5-C10 heteroarylalkyl group, and optionally substituted amine;
• wherein each of R3 and R4 is independently selected from the group consisting of optionally substituted branched C1-C22 alkyl and optionally substituted C2-C22 alkenyl;
• wherein each of R5, R6, R7, R8, R9, and R10 is independently selected from the group consisting of H, OH, halo, phenyl, benzyl, optionally substituted C1-C22 alkyl, optionally substituted C2-C22 alkenyl, and optionally substituted C2-C22 alkynyl;
• wherein each of x, y, and z is independently an integer selected from 0-10;
• wherein G and Q are each N;
• wherein each of m and n is 2;
• and
• wherein each of L1 and L2 is independently selected from the group consisting of OC(═O)— and C(═O)O—.