Suprametallogels and uses thereof
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).
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 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 ), —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, or 3;
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:
or a salt thereof.
8. The macromer of claim 1 , or a salt thereof, wherein Ring A is of the formula:
9. The macromer of claim 1 , or a salt thereof, wherein Ring A is of the formula:
10. The macromer of claim 1 , or a salt thereof, wherein Ring A is of the formula:
11. The macromer of claim 1 , or a salt thereof, wherein Ring A is of the formula:
12. The macromer of claim 1 , or a salt thereof, wherein Ring B is of the formula:
13. The macromer of claim 1 , or a salt thereof, wherein Ring B is of the formula:
14. The macromer of claim 1 , or a salt thereof, wherein Ring B is of the formula:
15. The macromer of claim 1 , or a salt thereof, wherein each instance of R A1 is hydrogen, and each instance of R A2 is hydrogen.
16. The macromer of claim 1 , or a salt thereof, wherein each one of m and n is 0.
17. The macromer of claim 1 , or a salt thereof, wherein each one of Z A and Z B is a bond.
18. The macromer of claim 1 , or a salt thereof, wherein each one of Z A and Z B is —C≡C—, —C≡C—C≡C—, or a moiety of the formula:
19. The macromer of claim 1 , or a salt thereof, wherein Y is a saturated or unsaturated, C 80-1500 hydrocarbon chain, optionally wherein not more than one half of all instances of the chain atoms of the saturated or unsaturated, C 80-1500 hydrocarbon chain are independently replaced with —O—, —S—, or —NR Y —, and optionally wherein one or more chain atoms of the saturated or unsaturated, C 80-1500 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.
20. The macromer of claim 1 , or a salt thereof, wherein Y is of the formula:
21. The macromer of claim 1 , or a salt thereof, wherein each chain atom, with any substituents thereon, of Y is independently —CH 2 —, —CH(unsubstituted C 1-6 alkyl)-, —C(unsubstituted C 1-6 alkyl) 2 -, —C(═O)—, —O—, —NH—, —N(unsubstituted C 1-6 alkyl)-, —N(nitrogen protecting group)-, or —CF 2 —.
22. The macromer of claim 7 , wherein the macromer is of the formula:
or a salt thereof.
23. The macromer of claim 7 , wherein the macromer is of the formula:
or a salt thereof.
24. The macromer of claim 7 , or a salt thereof, wherein Ring A is of the formula:
25. The macromer of claim 7 , or a salt thereof, wherein Ring A is of the formula:
26. The macromer of claim 7 , or a salt thereof, wherein Ring A is of the formula:
27. The macromer of claim 7 , or a salt thereof, wherein Ring A is of the formula:
28. The macromer of claim 7 , or a salt thereof, wherein each instance of R A1 is hydrogen, and each instance of R A2 is hydrogen.
29. The macromer of claim 7 , or a salt thereof, wherein each one of m and n is 0.
30. The macromer of claim 7 , or a salt thereof, wherein each one of Z A and Z B is a bond.
31. The macromer of claim 7 , or a salt thereof, wherein each one of Z A and Z B is —C≡C—, —C≡C—C≡C—, or a moiety of the formula:
32. The macromer of claim 7 , or a salt thereof, wherein Y is a saturated or unsaturated, C 80-1500 hydrocarbon chain, optionally wherein not more than one half of all instances of the chain atoms of the saturated or unsaturated, C 80-1500 hydrocarbon chain are independently replaced with —O—, —S—, or —NR Y —, and optionally wherein one or more chain atoms of the saturated or unsaturated, C 80-1500 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.
33. The macromer of claim 7 , or a salt thereof, wherein Y is of the formula:
34. The macromer of claim 7 , or a salt thereof, wherein each chain atom, with any substituents thereon, of Y is independently —CH 2 —, —CH(unsubstituted C 1-6 alkyl)—, —C (unsubstituted C 1-6 alkyl) 2 —, —C(═O)—, —O—, —NH—, —N(unsubstituted C 1-6 alkyl)—, —N(nitrogen protecting group)—, or —CF 2 —.
35. The macromer of claim 7 , wherein the macromer is of the formula:
or a salt thereof.