Suprametallogels and uses thereof

Patent metadata

Field	Value
Publication number	US-10023536-B2
Application number	US-201615270959-A
Country	US
Kind code	B2
Filing date	Sep 20, 2016
Priority date	Feb 7, 2014
Publication date	Jul 17, 2018
Grant date	Jul 17, 2018

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 macromer of Formula (B):

or a salt thereof, wherein:
each of

is Ring A, wherein Ring A is of the formula:

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, —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 ;
n is 0, 1, 2, 3, or 4;
Z A is a bond or a saturated or unsaturated, C 1-4 hydrocarbon chain, optionally wherein one or more chain atoms of the saturated or unsaturated, C 1-4 hydrocarbon chain are independently replaced with —O—, —S—, —NR ZA —, —N═, or ═N—, wherein each instance of R ZA is independently hydrogen, unsubstituted C 1-6 alkyl, or a nitrogen protecting group, and optionally wherein one or more chain atoms of the saturated or unsaturated, C 1-4 hydrocarbon chain are independently substituted with one or more substituents independently selected from the group consisting of ═O and halogen;
Z B is a bond or a saturated or unsaturated, C 1-4 hydrocarbon chain, optionally wherein one or more chain atoms of the saturated or unsaturated, C 1-4 hydrocarbon chain are independently replaced with —O—, —S—, —NR ZB —, —N═, or ═N—, wherein each instance of R ZB is independently hydrogen, unsubstituted C 1-6 alkyl, or a nitrogen protecting group, and optionally wherein one or more chain atoms of the saturated or unsaturated, C 1-4 hydrocarbon chain are independently substituted with one or more substituents independently selected from the group consisting of ═O and halogen; and
Y is a saturated or unsaturated, C 30-3000 hydrocarbon chain, optionally wherein one or more chain atoms of the saturated or unsaturated, C 30-3000 hydrocarbon chain are independently replaced with —O—, —S—, —NR Y —, ═N—, or —N═, wherein each instance of R Y is independently hydrogen, unsubstituted C 1-6 alkyl, or a nitrogen protecting group, and optionally wherein one or more chain atoms of the saturated or unsaturated, C 30-3000 hydrocarbon chain are independently substituted with one or more substituents independently selected from the group consisting of ═O, halogen, and unsubstituted C 1-6 alkyl.

2. The macromer of claim 1 , wherein the macromer is of the formula:

or a salt thereof.

3. The macromer of claim 1 , wherein the macromer is of the formula:

or a salt thereof.

4. The macromer of claim 1 , wherein the macromer is of the formula:

or a salt thereof.

5. The macromer of claim 1 , wherein the macromer is of the formula:

or a salt thereof.

6. The macromer of claim 1 , wherein the macromer is of the formula:

or a salt thereof.

7. A macromer of the formula:

each of

is Ring A, wherein Ring A is of the formula:

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 carbo

Assignees

• Massachusetts Inst Technology

Inventors

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

Classifications

• A61K47/22

  Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones · CPC title

• C07D213/30 Primary

  Oxygen atoms · CPC title

• C07F15/02

  Iron compounds · CPC title

• C07F15/006

  Palladium compounds · CPC title

• C07F15/0066

  without a metal-carbon linkage · CPC title