Inorganic particle conjugates
View Patent ↗The ionic conjugates include an inorganic particle electrostatically associated with a macromolecule which can interact specifically with predetermined chemical species or biological targets.
1. A composition comprising:
a semiconductor nanocrystal,
a linking group which has a distal end and a proximal end, the distal end being bound to an outer surface of the semiconductor nanocrystal and the proximal end comprising a first charged or ionizable moiety, wherein
the distal end comprises S, N, P, O, or O═P;
the first charged or ionizable moiety is selected from the group consisting of a hydroxide, an alkoxide, a carboxylate, a sulfonate, a phosphate, a phosphonate and a quaternary ammonium; and
the distal and proximal ends are connected by a spacer or a bond, and
a fusion protein comprising a second charged or ionizable moiety, wherein the first and second charged or ionizable moieties electrostatically associate the semiconductor nanocrystal with the fusion protein to form an ionic conjugate.
2. The composition of claim 1 , wherein the spacer is selected from a branched or unbranched C2-C100 alkylene, a branched or unbranched C2-C100 alkenylene, a branched or unbranched C2-C100 heterolkenylene, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocyclic, aryl, and heteroaryl.
3. The composition of claim 1 , wherein the semiconductor nanocrystal comprises a first semiconductor material, and wherein the first semiconductor material is a Group II-VI compound.
4. The composition of claim 1 , wherein the semiconductor nanocrystal is further bound to a plurality of linking groups each independently comprising a third charged or ionizable moiety.
5. The composition of claim 4 further comprising a plurality of macromolecules, each of the macromolecules comprising a fourth charged or ionizable moiety, wherein the plurality of macromolecules are associated with the semiconductor nanocrystal via electrostatic interaction with the plurality of semiconductor nanocrystal linking groups.
6. The composition of claim 1 , wherein the second charged or ionizable moiety is selected from the group consisting of a hydroxide, an alkoxide, a carboxylate, a sulfonate, a phosphate, a phosphonate and a quaternary ammonium.
7. The composition of claim 1 , wherein the linking group has the formula:
(R 1) a —R 2 —[(R 3 ) b (R4) c ] d
wherein
R 1 is selected from the group consisting of C1-C100 heteroalkyl, C2-C100 heteroalkenyl, heteroalkynyl, —OR, —SH, —NHR, —NR′R″, —N(O)HR, —N(O)R′R″, —PHR, —PR′R″, —P(NR′R″)NR′R″, —P(O)R′R″, —P(O)(NR′R″)NR′R″, —P(O)(OR′)OR″, —P(O)OR, —P(O)NR′R″, —P(S)(OR′)OR″, and —P(S)OR, wherein R, R′, R″ are independently selected from the group consisting of H, a branched or unbranched C1-C100 alkyl, a branched or unbranched C2-C100 alkenyl, a branched or unbranched C2-C100 alkynyl, a branched or unbranched C1-C100 heteroalkyl, a branched or unbranched C2-C100 heteroalkenyl, a branched or unbranched C2-C100 heteroalkynyl, with the proviso that when a is greater than 1 the R 1 groups can be attached to the R 2 or R 3 groups at the same or different atoms within those groups, the R 1 groups can be the same or different, or the R 1 groups can form a six, seven, eight, nine, or ten membered cycloalkyl, cycloalkenyl, heterocyclic, aryl, heteroaryl, or a six- to thirty-membered crown ether or heterocrown ether,
R 2 is selected from a bond, a branched or unbranched C2-C100 alkylene, a branched or unbranched C2-C100 alkenylene, a branched or unbranched C2-C100 heteroalkenylene, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocyclic, aryl, and heteroaryl;
R 3 is selected from a branched or unbranched C2-C100 alkylene, a branched or unbranched C2-C100 alkenylene, a branched or unbranched C2-C100 heteroalkenylene, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocyclic, aryl, and heteroaryl;
R 4 is selected from the group consisting of hydrogen, a carboxylate, a thiocarboxylate, an amide, a hydrazine, a sulfonate, a sulfoxide, a sulfone, a sulfite, a phosphate, a phosphonate, a phosphonimum ion, an alcohol, a thiol, an amine, an ammonium, an alkyl ammonium, a nitrate; and
a is 1 to 40, b is 0 to3, c is 1 to 30, d is 1 to 3, and when d is 2 or 3 the R 3 groups can be the same or different or can be linked together to form a five to ten members cycloalkyl, cycloalkenyl, heterocyclic, aryl, or heteroaryl.
8. The composition of claim 1 , wherein the linking group has the formula
HS—C 2 H 4 —CH(SH)—(C 4 H 8 )—COOH.
9. The composition of claim 1 , wherein the second charged or ionizable moiety is a leucine zipper.
10. The composition of claim 1 , wherein the second charged or ionizable moiety is polyaspartate.
11. The composition of claim 1 , wherein the fusion protein includes a maltose binding protein.
12. The composition of claim 1 , wherein the fusion includes an immunoglobulin G binding protein.
13. The composition of claim 1 , wherein the first semiconductor material is CdSe.
14. The composition of claim 13 , wherein the first semiconductor material is overcoated with a second semiconductor material.
15. A method of forming an ionic conjugate, comprising:
providing a semiconductor nanocrystal with a linking group having a distal end and a proximal end, wherein the distal end is bound to an outer surface of the semiconductor nanocrystal, and the proximal end comprises a first charged or ionizable moiety, and wherein the distal end comprises S, N, P, O, or O═P, the first charged or ionizable moiety is selected from the group consisting of a hydroxide, an alkoxide, a carboxylate, a sulfonate, a phosphate, a phosphonate and a quaternary ammonium, and the distal and proximal ends are connected by a spacer or a bond; and
contacting a fusion protein having a second charged or ionizable moiety with the semiconductor nanocrystal, wherein the first and second charged or ionizable moieties electrostatically associate the semiconductor nanocrystal with the fusion protein to form an ionic conjugate.
16. The method of claim 15 , wherein the first semiconductor material is overcoated with a second semiconductor material.
17. The method of claim 15 , wherein the spacer is selected from a branched or unbranched C2-C100 alkylene, a branched or unbranched C2-C100 alkenylene, a branched or unbranched C2-C100 heteroalkenylene, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocyclic, aryl, and heteroaryl.
18. The method of claim 15 , wherein the semiconductor nanocrystal comprises a first semiconductor material, wherein the first semiconductor material is a Group II-VI compound.
19. The method of claim 18 , wherein the first semiconductor material is CdSe.
20. The method of claim 19 , wherein the first semiconductor material is overcoated with a second semiconductor material.
21. The method of claim 15 , wherein the semiconductor nanocrystal is further bound to a plurality of linking groups each independently comprising a third charged or ionizable moiety.
22. The method of claim 21 , further comprising a plurality of macromolecules, each of the macromolecules comprising a fourth charged or ionizable moiety, wherein the plurality of macromolecules are associated with the semiconductor nanocrystal via electrostatic interaction with the plurality of linking groups.
23. The method of claim 15 , wherein the second charged or ionizable moiety is selected from the group consisting of a hydroxide, an alkoxide, a carboxylate, a sulfonate, a phosphate, a phosphonate and a quaternary ammonium.
24. The method of claim 15 , wherein the linking group has the formula:
(R 1 ) a —R 2 —[(R 3 ) b (R 4 ) c] d
wherein
R 1 is selected from the group consisting of C1-C100 heteroalkyl, C2-C100 heteroalkenyl, heteroalkynyl, —OR, —SH, —NHR, —NR′R″, —N(O)HR, —N(O)R′R″, —PHR, —PR′R″, —P(NR′R″)NR′R″, P(O)R′R″, P(O)(NR′R″)NR′R″, —P(O)(OR′)OR″, P(O)OR, P(O)NR′R″, —P(S)(OR′)OR″, and P(S)OR, wherein R, R′, R″ are independently selected from the group consisting of H, a branched or unbranched C1-C100 alkyl, a branched or unbranched C2-C100 alkenyl, a branched or unbranched C2-C100 alkynyl, a branched or unbranched C1-C100 heteroalkyl, a branched or unbranched C2-C100 heteroalkenyl, a branched or branched C2-C100 heteroalkynyl, with the proviso that when a is greater than 1 the R 1 group can be attached to the R 2 or R 3 groups at the same or different atoms within those groups, the R 1 groups can be the same or different, or the R 1 groups can form a six, seven, eight, nine, or ten membered cycloalkyl, cycloalkenyl, heterocyclic, aryl, heteroaryl, or a six- to thirty-membered crown ether or heterocrown ether;
R 2 is selected from a bond (i.e., R 2 is absent in which case R 1 attaches to R 3 ), a branched or unbranched C2-C100 alkylene, a branched or unbranched C2-C100 alkenylene, a branched or unbranched C2-C100 heteroalkenylene, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocyclic, aryl, and heteroaryl;
R 3 is selected from a branched or unbranched C2-C100 alkylene, a branched or unbranched C2-C100 alkenylene, a branched or unbranched C2-C100 heteroalkenylene, cycloalkyl, cycloalkenyl, cycloalkynyl, heterocyclic, aryl, and heteroaryl;
R 4 is selected from the group consisting of hydrogen, a carboxylate, a thiocarboxylate, and amid, an amine, a hydrazine, a sulfonate, a sulfoxide, a sulfone, a sulfite, a phosphate, a phosphonate, a phosphonium ion, an alcohol, a thiol, an amine, ammonium, an alkyl ammonium, a nitrate; and
a is 1 to 4, b is 0 to 3, c is 1 to 3, d is 1 to 3, and when d is 2 or 3 the R 3 groups can be the same or different or can be linked together to form a five to ten members cycloalkyl, cycloalkenyl, heterocyclic, aryl, or heteroaryl.
25. The method of claim 15 , wherein the linking group has the formula
HS—C 2 H 4 —CH(SH)—(C 4 H 8 )—COOH.
26. The method of claim 15 , wherein the second charged or ionizable moiety is a leucine zipper.
27. The method of claim 15 , wherein the second charged or ionizable moiety is polyaspartate.
28. The method of claim 15 , wherein the fusion protein includes a maltose binding protein.
29. The method of claim 15 , wherein the fusion protein includes an immunoglobulin G binding protein.