Abstract Bifunctional aromatic compounds which are capable of linking metal ions to biologically useful molecules. The bifunctional compounds are characterized as having a hydrazine or hydrazide group and a protein reactive group. The hydrazine or hydrazide group may be protected as a lower alkyl hydrazone. Conjugates of the bifunctional compounds with macromolecules are also described and labelled macromolecules comprised of the conjugates and metal ions are provided. Additionally, a method is provided for forming a labelled macromolecule by reacting a conjugate with a metal species The compounds and method of this invention are particularly useful in the fields of biology and medicine for imaging and/or therapy.
A hydrazine or hydrazide compound of the formula (I) or (II): ##STR5## wherein: A is a carbon or nitrogen atom; B is carbon or nitrogen atom except that only one of said terms A and B is nitrogen; D is a direct bond or ##STR6## E represents ##STR7## and F is ##STR8## or E and F together represent ##STR9## r is hydrogen or lower alkyl; R' and R" independently represent hydrogen and lower alkyl; and X is a negative counterion.
Claim 2
Dependent Claim
80 words
A hydrazine or hydrazide compound of the formula (I) or (II): ##STR5## wherein: A is a carbon or nitrogen atom; B is carbon or nitrogen atom except that only one of said terms A and B is nitrogen; D is a direct bond or ##STR6## E represents ##STR7## and F is ##STR8## or E and F together represent ##STR9## r is hydrogen or lower alkyl; R' and R" independently represent hydrogen and lower alkyl; and X is a negative counterion.
Claim 3
Dependent Claim
18 words
The compound of the claim 1 wherein D is a direct bond to the 4-position of the ring.
Claim 4
Dependent Claim
29 words
The compound of claim 2 wherein E is carbonyl and F is N-oxysuccinimidyl and X is selected from the group consisting of a halide, nitrate, trifluoroacetate, tetrafluoroborate and sulfate.
Claim 5
Dependent Claim
21 words
The compound of claim 2 wherein R is hydrogen or methyl, E is carbonyl, F is N-oxysuccinimidyl, and X is Cl.
Claim 6
Dependent Claim
18 words
The compound of claim 4 wherein one of A and B is carbon and the other is nitrogen.
Claim 7
Dependent Claim
16 words
The compound of claim 4 wherein A is carbon, B is nitrogen, and R is hydrogen.