A thiosuccinyl-crosslinked hemoglobin comprising a tetrameric hemoglobin and at least one thiosuccinyl crosslinking moiety of Formula 1: or a pharmaceutically acceptable salt or zwitterion thereof, wherein each N* independently represents a nitrogen selected from the group consisting of a nitrogen in a lysine residue side chain in the tetrameric hemoglobin and a nitrogen at a N-terminus in the tetrameric hemoglobin; and R 1 is alkyl, alkenyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, or -(CR 2) n Y, wherein n is an integer selected from 0-10; R for each instance is independently hydrogen, alkyl, aralkyl, alkenyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; or two instances of R taken together form a 3-6 membered cycloalkyl or heterocycloalkyl containing 1, 2, or 3 heteroatoms selected from N, O, and S; and Y is selected from the group consisting of OR 4, SR 4, N(R 4) 2, -(C=O)R 4, -(C=O)OR 4, -O(C=O)R 4, -O(C=O)OR 4, -(C=O)N(R 4) 2, -(NR 4)(C=O)R 4, - (NR 4)(C=O)OR 4, -O(C=O)N(R 4) 2, -O(C=NR 4)N(R 4) 2, -(NR 4)(C=O)N(R 4) 2, -(C=NR 4)N(R 4) 2, - (NR 4)(C=NR 4)N(R 4) 2, -(S=O)R 4, -S 2 R 4, -S 2 OR 4, -S 2 N(R 4) 2, -OS 2 R 4, - (NR 4)S 2 R 4, -OS 2 OR 4, -OS 2 N(R 4) 2, -(NR 4)S 2 N(R 4) 2, -(NR 4)S 2 OR 4, and - (CRR 2 R 3), wherein R 2 is hydrogen, alkyl, aralkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, OR 4, SR 4, N(R 4) 2, -(C=O)R 4, -(C=O)OR 4, -O(C=O)R 4, -O(C=O)OR 4, -(C=O)N(R 4) 2, - (NR 4)(C=O)R 4, -(NR 4)(C=O)OR 4, -O(C=O)N(R 4) 2, -O(C=NR 4)N(R 4) 2, -(NR 4)(C=O)N(R 4) 2, - (C=NR 4)N(R 4) 2, -(NR 4)(C=NR 4)N(R 4) 2, -(S=O)R 4, -S 2 R 4, -S 2 OR 4, -S 2 N(R 4) 2, - OS 2 R 4, -(NR 4)S 2 R 4, -OS 2 OR 4, -OS 2 N(R 4) 2, -(NR 4)S 2 N(R 4) 2, or - (NR 4)S 2 OR 4; R 3 is hydrogen, alkyl, aralkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, OR 4, SR 4, N(R 4) 2, -(C=O)R 4, -(C=O)OR 4, -O(C=O)R 4, -O(C=O)OR 4, -(C=O)N(R 4) 2, - (NR 4)(C=O)R 4, -(NR 4)(C=O)OR 4, -O(C=O)N(R 4) 2, -O(C=NR 4)N(R 4) 2, -(NR 4)(C=O)N(R 4) 2, - (C=NR 4)N(R 4) 2, -(NR 4)(C=NR 4)N(R 4) 2, -(S=O)R 4, -S 2 R 4, -S 2 OR 4, -S 2 N(R 4) 2, - OS 2 R 4, -(NR 4)S 2 R 4, -OS 2 OR 4, -OS 2 N(R 4) 2, -(NR 4)S 2 N(R 4) 2, or - (NR 4)S 2 OR 4; and R 4 for each instance is independently selected from the group consisting of hydrogen, alkyl, aralkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; or R 1 is a moiety selected from the group consisting of: and N 5 -(1-((carboxymethyl)amino)-1-oxo-3λ 3 -propan-2-yl)glutamine or a pharmaceutically acceptable salt thereof, wherein m is a whole number selected from 1-1000. or a pharmaceutically acceptable salt or zwitterion thereof, wherein each N* independently represents a nitrogen selected from the group consisting of a nitrogen in a lysine residue side chain in the tetrameric hemoglobin and a nitrogen at a N-terminus in the tetrameric hemoglobin; and R 1 is alkyl, alkenyl, cycloalkyl, heterocycloalkyl, aryl, aralkyl, heteroaryl, or -(CR 2) n Y, wherein n is an integer selected from 0-10; R for each instance is independently hydrogen, alkyl, aralkyl, alkenyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; or two instances of R taken together form a 3-6 membered cycloalkyl or heterocycloalkyl containing 1, 2, or 3 heteroatoms selected from N, O, and S; and Y is selected from the group consisting of OR 4, SR 4, N(R 4) 2, -(C=O)R 4, -(C=O)OR 4, -O(C=O)R 4, -O(C=O)OR 4, -(C=O)N(R 4) 2, -(NR 4)(C=O)R 4, - (NR 4)(C=O)OR 4, -O(C=O)N(R 4) 2, -O(C=NR 4)N(R 4) 2, -(NR 4)(C=O)N(R 4) 2, -(C=NR 4)N(R 4) 2, - (NR 4)(C=NR 4)N(R 4) 2, -(S=O)R 4, -S 2 R 4, -S 2 OR 4, -S 2 N(R 4) 2, -OS 2 R 4, - (NR 4)S 2 R 4, -OS 2 OR 4, -OS 2 N(R 4) 2, -(NR 4)S 2 N(R 4) 2, -(NR 4)S 2 OR 4, and - (CRR 2 R 3), wherein R 2 is hydrogen, alkyl, aralkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, OR 4, SR 4, N(R 4) 2, -(C=O)R 4, -(C=O)OR 4, -O(C=O)R 4, -O(C=O)OR 4, -(C=O)N(R 4) 2, - (NR 4)(C=O)R 4, -(NR 4)(C=O)OR 4, -O(C=O)N(R 4) 2, -O(C=NR 4)N(R 4) 2, -(NR 4)(C=O)N(R 4) 2, - (C=NR 4)N(R 4) 2, -(NR 4)(C=NR 4)N(R 4) 2, -(S=O)R 4, -S 2 R 4, -S 2 OR 4, -S 2 N(R 4) 2, - OS 2 R 4, -(NR 4)S 2 R 4, -OS 2 OR 4, -OS 2 N(R 4) 2, -(NR 4)S 2 N(R 4) 2, or - (NR 4)S 2 OR 4; R 3 is hydrogen, alkyl, aralkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, OR 4, SR 4, N(R 4) 2, -(C=O)R 4, -(C=O)OR 4, -O(C=O)R 4, -O(C=O)OR 4, -(C=O)N(R 4) 2, - (NR 4)(C=O)R 4, -(NR 4)(C=O)OR 4, -O(C=O)N(R 4) 2, -O(C=NR 4)N(R 4) 2, -(NR 4)(C=O)N(R 4) 2, - (C=NR 4)N(R 4) 2, -(NR 4)(C=NR 4)N(R 4) 2, -(S=O)R 4, -S 2 R 4, -S 2 OR 4, -S 2 N(R 4) 2, - OS 2 R 4, -(NR 4)S 2 R 4, -OS 2 OR 4, -OS 2 N(R 4) 2, -(NR 4)S 2 N(R 4) 2, or - (NR 4)S 2 OR 4; and R 4 for each instance is independently selected from the group consisting of hydrogen, alkyl, aralkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl; or R 1 is a moiety selected from the group consisting of: and N 5 -(1-((carboxymethyl)amino)-1-oxo-3λ 3 -propan-2-yl)glutamine or a pharmaceutically acceptable salt thereof, wherein m is a whole number selected from 1-1000.