Silicon containing detectable compounds and uses thereof
Disclosed herein, inter alia, are silicon containing detectable compounds and methods of use thereof. In an aspect is provided a monovalent nucleotide or monovalent nucleoside covalently bound to a monovalent form of a compound described herein (e.g., wherein the R13 moiety of a compound described herein has reacted with a bioconjugate reactive group to form a bioconjugate linker thereby covalently bonding the monovalent compound to the monovalent nucleotide or monovalent nucleoside).
1. An agent covalently bound to a compound, or salt thereof, via a bioconjugate linker, wherein said agent is a protein, carbohydrate, or virus, and said compound or salt thereof has the formula:
wherein
R 1 , R 8 , R 9 , R 10 , R 11 , and R 12 are independently hydrogen, halogen, —CCl 3 , —CBr 3 , —CF 3 , —CI 3 , —CHCl 2 , —CHBr 2 , —CHF 2 , —CHI 2 , —CH 2 Cl, —CH 2 Br, —CH 2 F, —CH 2 I, —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, NHC(O)H, —NHC(O)OH, —NHOH, —OCCl 3 , —OCF 3 , —OCBr 3 , —OCI 3 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , —OCHF 2 , —OCH 2 Cl, —OCH 2 Br, —OCH 2 I, —OCH 2 F, —N 3 , —SF 5 , —PO 3 H, substituted or unsubstituted alkyl, or substituted or unsubstituted heteroalkyl, or a bioconjugate linker;
R 2 and R 3 are independently substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, or a bioconjugate linker;
R 4 , R 5 , R 6 , and R 7 are independently hydrogen, halogen, —CF 3 , —CBr 3 , —CCl 3 , —CI 3 , —CHF 2 , —CHBr 2 , —CHCl 2 , —CHI 2 , —CH 2 F, —CH 2 Br, —CH 2 Cl, —CH 2 I, —OH, —COOH, —CONH 2 , —SH, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or a bioconjugate linker;
R 4 and R 5 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
R 6 and R 7 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
R 4 and R 9 substituents may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
R 7 and R 16 substituents may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
R 5 and R 11 substituents may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
R 6 and R 12 substituents may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
R 1 and R 9 substituents may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl; substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
R 8 and R 10 substituents may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl; substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
wherein one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and R 12 is a bioconjugate linker.
2. The agent of claim 1 , wherein the compound has the formula:
wherein L 1 is the bioconjugate linker and is the attachment point to the biomolecule.
3. The agent of claim 1 , wherein L 1 is a bond, —S(O) 2 —, —S(O) 2 NH—, —NHS(O) 2 —, —NH—, —O—, —S—, —C(O)—, —C(O)NH—, —NHC(O)—, —NHC(O)NH—, —C(O)O—, —OC(O)—, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, substituted or unsubstituted heteroarylene, or a divalent polymer.
4. The agent of claim 1 , wherein R 2 and R 3 are independently substituted or unsubstituted C 1 -C 6 alkyl, or substituted or unsubstituted 2 to 6 membered heteroalkyl.
5. The agent of claim 1 , wherein R 4 , R 5 , R 6 , and R 7 are independently hydrogen, substituted or unsubstituted C 1 -C 6 alkyl, or substituted or unsubstituted 2 to 6 membered heteroalkyl.
6. The agent of claim 1 , wherein R 4 and R 5 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted 3 to 6 membered heterocycloalkyl.
7. The agent of claim 1 , wherein R 6 and substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted 3 to 6 membered heterocycloalkyl.
8. The agent of claim 1 , wherein R 1 , R 8 , R 9 , R 10 , R 11 , and R 12 are independently hydrogen, halogen, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —SF 5 , —PO 3 H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, or a bioconjugate linker.
9. The agent of claim 1 , wherein the compound has the formula:
wherein L 1 is the bioconjugate linker and is the attachment point to the biomolecule.
10. The agent of claim 1 , wherein the compound has the formula:
wherein
R 14 and R 15 are independently halogen, —CCl 3 , —CBr 3 , —CF 3 , —CI 3 , —CHCl 2 , —CHBr 2 , —CHF 2 , —CHI 2 , —CH 2 Cl, —CH 2 Br, —CH 2 F, —CH 2 I, —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, NHC(O)H, —NHC(O)OH, —NHOH, —OCCl 3 , —OCF 3 , —OCBr 3 , —OCI 3 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , —OCHF 2 , —OCH 2 Cl, —OCH 2 Br, —OCH 2 I, —OCH 2 F, —N 3 , —SF 5 , —PO 3 H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, or a bioconjugate linker;
wherein no more than one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 14 and R 15 is a bioconjugate linker; and
z14 and z15 are each independently an integer from 0 to 8.
11. The agent of claim 1 , wherein the compound has the formula:
wherein
R 16 and R 17 are independently halogen, —CCl 3 , —CBr 3 , —CF 3 , —CI 3 , —CHCl 2 , —CHBr 2 , —CHF 2 , —CHI 2 , —CH 2 Cl, —CH 2 Br, —CH 2 F, —CH 2 I, —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, NHC(O)H, —NHC(O)OH, —NHOH, —OCCl 3 , —OCF 3 , —OCBr 3 , —OCI 3 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , —OCHF 2 , —OCH 2 Cl, —OCH 2 Br, —OCH 2 I, —OCH 2 F, —N 3 , —SF 5 , —PO 3 H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, or a bioconjugate linker;
wherein no more than one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 16 , and R 17 is a bioconjugate linker; and
z16 and z17 are independently an integer from 0 to 4.
12. The agent of claim 11 , wherein the compound has the formula:
13. The agent of claim 1 , wherein the compound has the formula:
wherein,
Ring A and Ring B are independently a heterocycloalkyl;
R 34 and R 36 are independently halogen, —CCl 3 , —CBr 3 , —CF 3 , —CI 3 , —CHCl 2 , —CHBr 2 , —CHF 2 , —CHI 2 , —CH 2 Cl, —CH 2 Br, —CH 2 F, —CH 2 I, —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, NHC(O)H, —NHC(O)OH, —NHOH, —OCCl 3 , —OCF 3 , —OCBr 3 , —OCI 3 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , —OCHF 2 , —OCH 2 Cl, —OCH 2 Br, —OCH 2 I, —OCH 2 F, —N 3 , —SF 5 , —PO 3 H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, or a bioconjugate linker;
wherein no more than one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 34 , and R 36 is a bioconjugate linker; and
z34 and z36 are each independently an integer from 0 to 12.
14. The agent of claim 13 , wherein Ring A and Ring B are each independently aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, or morpholinyl.
15. A compound, or salt thereof, having the formula:
wherein
R 1 , R 8 , R 9 , R 10 , R 11 , and R 12 are independently L 1 -R 13 , hydrogen, halogen, —CCl 3 , —CBr 3 , —CF 3 , —CI 3 , —CHCl 2 , —CHBr 2 , —CHF 2 , —CHI 2 , —CH 2 Cl, —CH 2 Br, —CH 2 F, —CH 2 I, —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, NHC(O)H, —NHC(O)OH, —NHOH, —OCCl 3 , —OCF 3 , —OCBr 3 , —OCI 3 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , —OCHF 2 , —OCH 2 Cl, —OCH 2 Br, —OCH 2 I, —OCH 2 F, —N 3 , —SF 5 , —PO 3 H, substituted or unsubstituted alkyl, or substituted or unsubstituted heteroalkyl;
R 2 and R 3 are independently L 1 -R 13 , substituted or unsubstituted alkyl, or substituted or unsubstituted heteroalkyl;
R 4 , R 5 , R 6 , and R 7 are independently -L 1 -R 13 , hydrogen, halogen, —CF 3 , —CBr 3 , —CCl 3 , —CI 3 , —CHF 2 , —CHBr 2 , —CHCl 2 , —CHI 2 , —CH 2 F, —CH 2 Br, —CH 2 Cl, —CH 2 I, —OH, —COOH, —CONH 2 , —SH, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 4 and R 9 substituents may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
R 7 and R 10 substituents may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
R 5 and R 11 substituents may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
R 6 and R 12 substituents may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
R 1 and R 9 substituents may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl; substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
R 8 and R 10 substituents may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl; substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
wherein one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and R 12 is L 1 -R 13 ;
R 13 is —NH 2 ,
and
L 1 is a covalent linker or a bond.
16. The compound of claim 15 , having the formula:
17. A nucleotide bound to a monovalent compound, wherein said monovalent compound has the formula:
wherein,
R 1 , R 8 , R 9 , R 10 , R 11 , and R 12 are independently hydrogen, halogen, —CCl 3 , —CBr 3 , —CF 3 , —CI 3 , —CHCl 2 , —CHBr 2 , —CHF 2 , —CHI 2 , —CH 2 Cl, —CH 2 Br, —CH 2 F, —CH 2 I, —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, NHC(O)H, —NHC(O)OH, —NHOH, —OCCl 3 , —OCF 3 , —OCBr 3 , —OCI 3 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , —OCHF 2 , —OCH 2 Cl, —OCH 2 Br, —OCH 2 I, —OCH 2 F, —N 3 , —SF 5 , —PO 3 H, substituted or unsubstituted alkyl, or substituted or unsubstituted heteroalkyl;
R 2 and R 3 are independently substituted or unsubstituted alkyl, or substituted or unsubstituted heteroalkyl;
R 4 , R 5 , R 6 , and R 7 are independently hydrogen, halogen, —CF 3 , —CBr 3 , —CCl 3 , —CI 3 , —CHF 2 , —CHBr 2 , —CHCl 2 , —CHI 2 , —CH 2 F, —CH 2 Br, —CH 2 Cl, —CH 2 I, —OH, —COOH, —CONH 2 , —SH, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 4 and R 5 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
R 6 and R 7 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
R 4 and R 9 substituents may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
R 7 and R 10 substituents may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
R 5 and R 11 substituents may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
R 6 and R 12 substituents may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
R 1 and R 9 substituents may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl; substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;
R 8 and R 10 substituents may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl; substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl; and
L 1 is a covalent linker.
18. The nucleotide of claim 17 , wherein L 1 is a cleavable linker.
19. A method of detecting a nucleic acid molecule, said method comprising contacting a nucleic acid molecule with a nucleotide of claim 17 , exposing the nucleotide to an absorption light, and detecting an emission wavelength.
20. A method of detecting the agent of claim 1 , said method comprising exposing the compound to an absorption light, and detecting an emission wavelength, thereby detecting the agent.
21. The agent of claim 1 , wherein the agent is an antibody or antibody fragment.