Chiral TACN/NOTA compounds/derivatives with and without metals for application

A chiral NOTA chelator of Formula 1:

• or a pharmaceutically acceptable salt or zwitterion thereof, wherein
• R1 is selected from the group consisting of hydrogen, alkyl, alkene, alkyne, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, araalkyl, and —(CR2)nY, wherein n is a whole number selected from 1-10;
• each R is independently hydrogen, alkyl, cycloalkyl, or aryl;
• or two R taken together with the carbon(s) to which they are attached form a 3-6 membered cycloalkyl;
• and Y is hydrogen, alkyl, alkene, alkyne, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cyano, halide, —N3, —R5, —OR3, —OP(OR3)3, —SR3, —NR32, —(C═O)OR3, —O(C═O)R3, —O(C═O)OR3, —(NR3)(C═O)R3, —(C═O)NR32, —O(C═O)NR32, —(NR3)(C═O)OR3, —(NR3)(C═O)NR32, or —(NR3)(C═NR3)NR32, wherein R3 for each instance is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl heterocyloalkyl, aryl, and heteroaryl;
• or two R3 taken together with the atom(s) they are attached form a 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, or 5 membered heteroaryl;
• or R1 is a side chain of a naturally occurring amino acid or the side chain of a D-isomer of a naturally occurring amino acid;
• or R1 is a moiety having the structure:
• wherein X is azide, alkyne, halide, tosylate, mesylate, or hydroxyl;
• and
• R2 is —(C═O)OH, —(C═O)NHR5, or —(CH2)mZ, wherein m is a whole number selected from 2-8;
• R5 is a targeting agent;
• and Z is moiety of Formula 2:
• or a pharmaceutically acceptable salt or zwitterion thereof;
• or R2 is a moiety of Formula 3:
• or a pharmaceutically acceptable salt or zwitterion thereof, wherein R6 for each occurrence is independently hydrogen, alkyl, alkene, alkyne, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cyano, halide, —N3, —R5, —OR3, —OP(OR3)3, —SR3, —NR32, —(C═O)OR3, —O(C═O)R3, —O(C═O)OR3, —(NR3)(C═O)R3, —(C═O)NR32, —O(C═O)NR32, —(NR3)(C═O)OR3, —(NR3)(C═O)NR32, or —(NR3)(C═NR3)NR32, wherein R3 for each instance is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl heterocyloalkyl, aryl, and heteroaryl;
• or two R3 taken together with the atom(s) they are attached form a 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, or 5 membered heteroaryl;
• or R6 is a moiety of Formula 4:
• wherein p is a whole number selected from 1-6;
• each A2 is independently —CO2R5, —NHR5, —OR5, N3, or alkyne;
• and R4 is hydrogen or alkyl, with the proviso that if one R2 is —(CH2)2Z and four R2 are each —(C═O)OH, then each R1 cannot be hydrogen;
• and if three R2 are each —(C═O)OH, then each R1 cannot be hydrogen.