Hemoglobin-based oxygen carrier compositions

A multimerized hemoglobin (Hb) composition, comprising two or more modified Hb, wherein each modified Hb independently comprises:

• at least two subunits of a Hb intramolecularly crosslinked with a compound of formula (I)
• or a salt, a stereoisomer, or a deuterated form thereof,
• wherein:
• X is C1-24 alkylene, C2-24 alkenylene, C2-24 alkynylene, C3-9 cycloalkylene, C3-9 cycloalkenylene, 5-12 membered heterocyclylene containing 1 or 2 heteroatoms selected from N, S, or O, heteroarylene, or -L1-NRA-L2-, wherein X is optionally substituted with 1-6 R3 as permitted by valency;
• R1 and R2 are each independently —OH, halogen, or a leaving group;
• each R3 is independently —OH, —CN, —NO2, halogen, oxo, —C1-6 alkyl, —C1-6 haloalkyl, —O(C1-6 alkyl), —S(C1-6 alkyl), —SO(C1-6 alkyl), —SO2(C1-6 alkyl), —(C1-12 alkylene)-N3, —(C1-12 alkylene)-(OCH2CH2)m—(CH2)n—N3, —C(O)NH—(C1-12 alkylene)-(OCH2CH2)m (CH2)n—N3, —NHC(O)—(C1-12 alkylene)-(OCH2CH2)m—(CH2)n—N3, —O—(C1-12 alkylene)-(OCH2CH2)m—(CH2)n—N3, —S—(C1-12 alkylene)-(OCH2CH2)m—(CH2)n—N3, or —C(O)—R1, wherein each alkyl or alkylene is optionally and independently substituted with —C1-6 alkyl, —OH, —CN, —NO2, or halogen;
• RA is H, —C1-6 alkyl, aryl, —C(O)-aryl, —SO2(C1-6 alkyl), —SO2-aryl, or —(C1-6 alkylene)-(OCH2CH2)m—(CH2)n—N3, wherein each alkyl, aryl, or alkylene is optionally and independently substituted with —C1-6 alkyl, —OH, —CN, —NO2, or halogen;
• L1 and L2 are each independently C1-12 alkylene, C2-12 alkenylene, C2-12 alkynylene, C3-9 cycloalkylene, C3-9 cycloalkenylene, arylene, or heteroarylene, wherein L1 and L2 are optionally and independently substituted with 1-3 R3 as permitted by valency;
• each m is independently an integer of 1-200;
• and
• each n is independently an integer of 0-50.