Suprametallogels and uses thereof

Patent metadata

Field	Value
Publication number	US-9447129-B2
Application number	US-201514617747-A
Country	US
Kind code	B2
Filing date	Feb 9, 2015
Priority date	Feb 7, 2014
Publication date	Sep 20, 2016
Grant date	Sep 20, 2016

Abstract

The disclosure provides nanostructures (e.g., nanospheres and nano-paddlewheels) formed through transition metal-ligand (e.g., Pd(II)-, Ni(II)-, or Fe(II)-ligand of Formula (A)) coordination and junction self-assembly. The disclosure also provides supramolecular complexes that include the nanostructures connected by divalent linkers Y. The provided supramolecular complexes are able to form gels (e.g., hydrogels). The gels are suprametallogels and exhibited excellent mechanical properties without sacrificing self-healing and showed high robustness and storage modulus. The present disclosure further provides compositions (e.g., gels) that include the nanostructures or supramolecular complexes and optionally an agent (e.g., small molecule), where the nanostructures and the nanostructure moieties of the supramolecular complexes may encapsulate and slowly release the agent. The nanostructures, supramolecular complex, and compositions may be useful in delivering an agent to a subject, tissue, or cell, as super-absorbent materials, and in treating a disease (e.g., a genetic diseases, proliferative disease (e.g., cancer or benign neoplasm), hematological disease, neurological disease, gastrointestinal disease (e.g., liver disease), spleen disease, respiratory disease (e.g., lung disease), painful condition, genitourinary disease, musculoskeletal condition, infectious disease, inflammatory disease, autoimmune disease, psychiatric disorder, or metabolic disorder).

First claim

What is claimed is:

1. A supramolecular complex comprising:
(a) two or more instances of a nanostructure, wherein each instance of the nanostructure comprises:
(i) x instances of a transition metal ion, wherein x is an integer between 2 and 60, inclusive; and
(ii) 2x instances of a ligand of Formula (A):

wherein:
Ring A is a substituted or unsubstituted phenyl ring or a substituted or unsubstituted, 5- or 6-membered, monocyclic heteroaryl ring;
each instance of X A , X B , X C , and X D is independently O, S, N, NR A1 , C, or CR A2 ;
X E is absent, N, or CR A2 ;
each instance of R A1 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —C(═O)R a , —C(═O)OR a , —C(═O)N(R a ) 2 , or a nitrogen protecting group;
each instance of R A2 is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR a , —N(R a ) 2 , —SR a , —CN, —SCN, —C(═NR a )R a , —C(═NR a )OR a , —C(═NR a )N(R a ) 2 , —C(═O)R a , —C(═O)OR a , —C(═O)N(R a ) 2 , —NO 2 , —NR a C(═O)R a , —NR a C(═O)OR a , —NR a C(═O)N(R a ) 2 , —OC(═O)R a , —OC(═O)OR a , or —OC(═O)N(R a ) 2 ;
each instance of R a is independently hydrogen, substituted or unsubstituted acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom, or two instances of R a are joined to form a substituted or unsubstituted heterocyclic or substituted or unsubstituted heteroaryl ring;
each instance of R B is independently halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —OR a , —N(R a ) 2 , —SR a , —CN, —SCN, —C(═NR a )R a , —C(═NR a )OR a , —C(═NR a )N(R a ) 2 , —C(═O)R a , —C(═O)OR a , —C(═O)N(R a ) 2 , —NO 2 , —NR a C(═O)R a , —NR a C(═O)OR a , —NR a C(═O)N(R a ) 2 , —OC(═O)R a , —OC(═O)OR a , or —OC(═O)N(R a ) 2 ;
m is 0, 1, 2, 3, or 4;
each instance of R C is independently halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —N(R a ) 2 , —SR a , —CN, —SCN, —C(═NR a )R a , —C(═NR a )OR a , —C(═NR a )N(R a ) 2 , —C(═O)R a , —C(═O)OR a , —C(═O)N(R a ) 2 , —NO 2 , —NR a C(═O)R a , —NR a C(═O)OR a , —NR a C(═O)N(R a ) 2 , —OC(═O)R a , —OC(═O)OR a , or —OC(═O)N(R a ) 2 ;
n is 0, 1, 2, 3, or 4;
Z A is a bond or a substituted or unsubstituted C 1-4 hydrocarbon chain, optionally wherein one or more chain atoms are independently replaced with —O—, —S—, —NR ZA —, —N═, or ═N—, wherein each instance of R ZA is independently hydrogen, substituted or unsubstituted C 1-6 alkyl, or a nitrogen protecting group;
Z B is a bond or a substituted or unsubstituted C 1-4 hydrocarbon chain, optionally wherein one or more chain atoms are independently replaced with —O—, —S—, or —NR ZB —, wherein each instance of R ZB is independently hydrogen, substituted or unsubstituted C 1-6 alkyl, or a nitrogen protecting group;

wherein each instance of the transition metal ion and two instances of the ligand of Formula (A) form through coordination bonds a coordination complex;
wherein the x instances of the transition metal ion and the 2x instances of the ligand of Formula (A) form through the coordination bonds a substantially spherical structure or paddlewheel structure;
wherein each of the coordination bonds is formed between an instance of the transition metal ion and the nitrogen atom labeled with 1′ or 1″ of an instance of the ligand of Formula (A); and
wherein the average outer diameter of the nanostructure is between about 1 nm and about 100 nm, inclusive; and

(b) at least one instance of Y, wherein:
each instance of Y is independently a substituted or unsubstituted, saturated or unsaturated C 30-3000 hydrocarbon chain, optionally wherein one or more chain atoms are independently replaced with —O—, —S—, —NR Y —, ═N—, or —N═, wherein each instance of R Y is independently hydrogen, substituted or unsubstituted C 1-6 alkyl, or a nitrogen protecting group;
each instance of Y is independently directly covalently attached to an instance of the ligand of Formula (A) and directly covalently attached to another instance of the ligand of Formula (A); and
at least two instances of the nanostructure are directly covalently connected by at least one instance of Y.

2. The supramolecular complex of claim 1 , wherein the ligand of Formula (A) is of the formula:

3. The supramolecular complex of claim 2 , wherein the ligand of Formula (A) is of the formula:

4. The supramolecular complex of claim 2 , wherein the ligand of Formula (A) is of the formula:

5. The supramolecular complex of claim 1 , wherein the ligand of Formula (A) is of the formula:

6. The supramolecular complex of claim 1 , wherein the ligand of Formula (A) is of the formula:

7. The supramolecular complex of claim 1 , wherein the nanostructure is of Formula (I-A) as shown in FIG. 29 ,
or a salt thereof, wherein:
each instance of the black dot represents the transition metal ion;
each instance of the gray line represents the ligand of Formula (A); and
each instance of the black line represents the coordination bond.

8. The supramolecular complex of claim 1 , wherein the nanostructure is of Formula (I-B) as shown in FIG. 30 ,
or a salt thereof, wherein:
each instance of the black dot represents the transition metal ion; and
each instance of the gray line represents the ligand of Formula (A).

9. The supramolecular complex of claim 1 , wherein x is 2, 12, or 24.

10. The supramolecular complex of claim 1 , wherein X E is N, C, or CR A2 .

11. The supramolecular complex of claim 1 , wherein the transition metal ion is Pd(II), Ni(II), or Fe(II).

12. The supramolecular complex of claim 1 ,

Assignees

• Massachusetts Inst Technology

Inventors

• Johnson Jeremiah A
• Holten-Andersen Niels
• Grindy Scott Charles
• Kawamoto Ken
• Zhukhovitskiy Aleksandr V

Classifications

• C08G83/008

  Supramolecular polymers · CPC title

• C07F15/0066 Primary

  without a metal-carbon linkage · CPC title

• C07D213/30 Primary

  Oxygen atoms · CPC title

• C07F15/006

  Palladium compounds · CPC title

• C07F15/04

  Nickel compounds · CPC title