Compositions for sialic acid sensing, cancer cell imaging, and methods of use thereof

Patent metadata

Field	Value
Publication number	US-2025231188-A1
Application number	US-202519017095-A
Country	US
Kind code	A1
Filing date	Jan 10, 2025
Priority date	Jan 12, 2024
Publication date	Jul 17, 2025
Grant date	—

Abstract

Compounds, particularly compounds capable of sensing and/or imaging glycans (such as sialic acids, e.g., mono-sialic acids, disialosides, trisialosides, polysialic acids), and/or cancer cells, and differentiating cancer cells from normal cells, are disclosed. The compounds are d8 or d10 metal complexes or salts thereof. The metal complexes can bind to glycans (such as sialic acids, e.g., mono-sialic acids, disialosides, trisialosides, polysialic acids), and/or cancer cells. The binding interaction induces accumulation and supramolecular self-assembly of the metal complexes, thereby causing changes in the photophysical properties of the metal complexes.

First claim

We claim:

1 . A compound comprising one or more metal centers having d 8 or d 10 electronic configuration and one or more coordinating ligands comprising one or more donor atoms, wherein:
(a) the one or more metal centers have a coordination number of 2, 3, or 4, and are selected from Pt(II), Pd(II), Ni(II), Ir(I), Rh(I), Au(III), Ag(III), Cu(III), Ni(0), Pd(0), Pt(0), Cu(I), Ag(I), Au(I), Zn(II), Cd(II), Hg(II), and a combination thereof; and (b) the one or more one donor atoms are selected from the group containing carbon (C), nitrogen (N), oxygen (O), phosphorus (P), sulfur (S), arsenic (As), and selenium (Se).

2 . The compound of claim 1 , having a chemical structure:

wherein: (a) M is a metal center selected from Pt(II), Pd(II), Ni(II), Ir(I), Rh(I), Au(III), Ag(III), and Cu(III), (b) L 1 , L 2 , L 3 , and L 4 represent the one or more coordinating ligands, wherein each ligand can offer at least one donor atom for coordination to the metal center; (c) n+/− is a charged state of the compound, wherein n is zero or a positive integer, such as 1, 2, 3, 4, and 5; (d) X is a counterion for charge neutrality of the compound, wherein when X m−/+ is an anion denoted as X m− , X m− is preferably selected from chloride (Cl − ), hexafluorophosphate (PF 6 − ), nitrate (NO 3 − ), perchlorate (ClO 4 − ), tetrafluoroborate (BF 4 − ), tetraphenylborate (B(C 6 H 5 ) 4 − ), triflate (CF 3 SO 3 − ), dihydrogenphosphate (H 2 PO 4 2− ), sulfate (SO 4 2− ), hydrogenphosphate (HPO 4 2− ), phosphate (PO 4 3− ), and derivatives thereof, wherein when X m−/+ is a cation denoted as X m+ , X m+ is preferably selected from K + , Na + , Ca 2+ , Mg 2+ , bis(triphenylphosphine)iminium ([(C 6 H 5 ) 3 P) 2 N] + ), phosphonium, pyridinium ([C 5 H 5 NH] + ), quaternary ammonium cations, and derivatives thereof; (e) m−/+ is a charged state of the counterion, wherein m is zero or a positive integer, such as 1, 2, 3, 4, and 5, wherein m=n or m≠n; (f) n/m represents a stoichiometry of the counterions in Formula I; and (g) the four dashed lines represent an optional independent covalent linking between two ligands, an optional independent fusion of ring moieties from two ligands, or a combination thereof.

3 . The compound of claim 2 , wherein L 1 , L 2 , L 3 , and L 4 are independently selected from C 6 -C 50 arenes or C 3 -C 50 heteroarenes, such as five-membered arenes and their derivatives, include but are not limited to, furan, pyrrole, thiophene, imidazole, pyrazole, oxazole, isoxazole, thiazole, benzofuran, isobenzofuran, indole, isoindole, benzothiophene, benzo[c]thiophene, benzimidazole, purine, indazole, benzisoxazole, benzothiazole; and/or six-membered arenes and their derivatives, include but are not limited to, benzene, pyridine, pyrazine, pyrimidine, pyridazine, 1,2,3-triazine, naphthalene, anthracene, quinoline, isoquinoline, quinoxaline, acridine, quinazoline, cinnoline, phthalazine, 1,2,4-triazine, 1,3,5-triazine, bipyridine, terpyridine, 2,6-bis(benzimidazol-2′-yl)pyridine, carbazole, dibenzothiophene, dibenzofuran, fluorene, halide, alkylamine, arylamine, alkylphosphine, arylphosphine, alkylarsine, arylarsine, SCN − wherein S is a donor atom, O—NO 2 − wherein O is a donor atom, N 3 − , O 2 − , S 2 − , H 2 O, O—NO − wherein O is a donor atom, NCS − wherein N is a donor atom, NH 3 , NO 2 − wherein N is a donor atom, N≡C − , CO wherein C is a donor atom, R—C≡C − —, RO − —, RS − —, RSe − —, N═N═N—R, N—C—R wherein N is a donor atom, C≡N—R wherein C is a donor atom, NR 1 R 2 R 3 , PR 1 R 2 R 3 , and AsR 1 R 2 R 3 , wherein R, R 1 , R 2 , and R 3 are independently selected from hydrogen, substituted or unsubstituted C 1 -C 30 alkyl, C 2 -C 30 alkenyl, C 2 -C 30 alkynyl, C 3 -C 30 aryl, C 3 -C 30 heteroaryl, C 1 -C 30 alkoxy, C 3 -C 30 aryloxy, C 3 -C 30 arylthio, C 1 -C 30 alkylthio, C 2 -C 30 carbonyl, C 1 -C 30 carboxyl, amino, amido, or polyaryl (containing fused or non-fused ring moieties).

4 . The compound of claim 2 , wherein the dashed lines stand for an optional linking between two ligands; or an optional fusion of rings from different ligands.

5 . The compound of claim 1 , having a chemical structure:

[

L
5

⁢
—
⁢

M
′

⁢
—
⁢

L
6

]

n
+

/
-

⁢

(

n
m

)

⁢

X

m
-

/
+

Formula
⁢

II

wherein:
(a) M′ is a metal center selected from Ni(O), Pd(O), Pt(O), Cu(I), Ag(I), Au(I), Zn(II), Cd(II) and Hg(II); and
(b) L 5 and L 6 represent the one or more coordinating ligands, wherein each ligand can offer at least one donor atom for coordination to the metal center;
(c) L 5 and L 6 are independently selected from C 6 -C 50 arenes or C 3 -C 50 heteroarenes, such as five-membered arenes and their derivatives, include but are not limited to, furan, pyrrole, thiophene, imidazole, pyrazole, oxazole, isoxazole, thiazole, benzofuran, isobenzofuran, indole, isoindole, benzothiophene, benzo[c]thiophene, benzimidazole, purine, indazole, benzisoxazole, benzothiazole; and/or six-membered arenes and their derivatives, include but are not limited to, benzene, pyridine, pyrazine, pyrimidine, pyridazine, 1,2,3-triazine, naphthalene, anthracene, quinoline, isoquinoline, quinoxaline, acridine, quinazoline, cinnoline, phthalazine, 1,2,4-triazine, 1,3,5-triazine, bipyridine, terpyridine, 2,6-bis(benzimidazol-2′-yl)pyridine, carbazole, dibenzothiophene, dibenzofuran, fluorene, halide, alkylamine, arylamine, alkylphosphine, arylphosphine, alkylarsine, arylarsine, SCN − wherein S is a donor atom, O—NO 2 − wherein O is a donor atom, N 3 − , O 2 − , S 2 − , H 2 O, O—NO − wherein O is a donor atom, NCS − wherein N is a donor atom, NH 3 , NO 2 − wherein N is a donor atom, N≡C − , CO wherein C is a donor atom, R—C≡C − —, RO − —, RS − —, RSe − —, N═N═N—R, N≡C—R wherein N is a donor atom, C≡N—R wherein C is a donor atom, NR 1 R 2 R 3 , PR 1 R 2 R 3 , and AsR 1 R 2 R 3 , wherein R, R 1 , R 2 , and R 3 are independently se

Assignees

• Univ Hong Kong

Inventors

• Yam Vivian Wing-Wah
• Guo Jungu
• Law Sin-Yee

Classifications

• G01N33/5759 Primary

  involving compounds localised on the membrane of tumour or cancer cells · CPC title

• G01N21/6428

  Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" (in vivo A61B5/00; immunoassay G01N33/53) · CPC title

• G01N21/64

  Fluorescence; Phosphorescence · CPC title

• C07F3/14

  Heterocyclic substances containing mercury · CPC title

• C07F3/00

  Compounds containing elements of Groups 2 or 12 of the Periodic Table · CPC title