Photoacid generators for the synthesis of oligo-DNA in a polymer matrix
View Patent ↗Compounds represented by the following structural formulas can be used as photoacid generators: Such compounds are useful, for example, in fabricating arrays of polymers.
1. A composition comprising a compound represented by Structural Formula (III):
or a salt thereof, wherein:
R 8 is a substituted sulfonyl, acetyl or benzoyl group;
R 9 is —H, —COOR, a substituted alkyl group or an alkenyl or aryl group;
R 10 is —NRR′, —COOR, an alkyl or alkenyl group or a substituted alkoxy or aryl group; and
R and R′ are independently —H or an alkyl, alkenyl or aryl group, and a sensitizer.
2. The compound of claim 1 , wherein R 9 is a substituted alkyl group or an alkenyl or aryl group.
3. The compound of claim 1 , wherein R 10 is an alkyl or alkenyl group or a substituted alkoxy or aryl group.
4. The compound of claim 1 , wherein R 9 is a substituted alkyl group or an alkenyl or aryl group and R 10 is an alkyl or alkenyl group aor a substituted alkoxy or aryl group.
5. The composition of claim 2 , wherein the sensitizer is isopropylthioxanthone or 10H-phenoxazine.
6. The composition of claim 2 , wherein the sensitizer compound concentration ratio is between 1.1 and 5.
7. The composition of claim 2 , further comprising an acid scavenger.
8. The composition of claim 2 , wherein the composition is in the form of a film.
9. The composition of claim 2 , further comprising one or more additional commercially available photoacid generators.
10. A method of generating acid, comprising exposing to light of an appropriate wavelength a compound represented by Structural Formula (III):
or a salt thereof, wherein:
R 8 is a substituted sulfonyl, acetyl or benzoyl group;
R 9 is —H, —COOR, a substituted alkyl group or an alkenyl or aryl group;
R 10 is —NRR′, —COOR, an alkyl or alkenyl group or a substituted alkoxy or aryl group;
and
R and R′ are independently —H or an alkyl, alkenyl or aryl group, wherein the wavelength is greater than 310 nm.
11. The method according to claim 10 , wherein the wavelength is between 330 nm and 365 nm.
12. A method of manufacturing a polymer array, which comprises:
(a) providing a substrate comprising a reactive group protected by an acid labile protective group;
(b) coating the substrate with a film comprising a photoacid generator represented by Structural Formula (III):
or a salt thereof, wherein:
R 8 is a substituted sulfonyl, acetyl or benzoyl group;
R 9 is —H, —COOR, a substituted alkyl group or an alkenyl or aryl group;
R 10 is —NRR′, —COOR, an alkyl or alkenyl group or a substituted alkoxy or aryl group; and
R and R′ are independently —H or an alkyl, alkenyl or aryl group; and
(c) activating the photoacid generator by application of light of a wavelength greater than 310 nm.
13. The method according to claim 12 , wherein the acid labile protective group is dimethoxytrityl (DMT) or di-tert-butyl dicarbonate (t-BOC) which protects a hydroxyl group.
14. The method according to claim 12 , further comprising:
(d) exposing the reactive to the acid such that the protective group is removed, yielding an exposed reactive group;
(e) contacting the exposed reactive group with a monomer, thereby coupling the monomer to the exposed reactive group; and
(f) repeating steps (b) through (e) to create a polymer.
15. The method according to claim 14 , wherein in step (d) the protective group is exposed to the acid for between 5 and 15 minutes.
16. The method according to claim 14 , wherein in step (d) the protective group is exposed to the acid for 1 hour.
17. The method according to claim 12 , wherein no heating step is employed.
18. The method according to claim 14 , wherein the monomer is a nucleotide and wherein the rate of depurination is less than 25%.
19. The method according to claim 12 , wherein the wavelength is between 330 nm and 365 nm.
20. The method according to claim 14 , wherein the monomer is selected from the group consisting of: nucleotide, peptide and peptide nucleic acid.
21. The method according to claim 12 , wherein the film comprises poly(methyl methacrylate).
22. The method according to claim 14 , wherein the polymers are at least 25 monomers in length or wherein steps (a) through (c) are repeated at least 25 times.
23. The method according to claim 18 , wherein the polymers are between 60 and 150 monomers in length or wherein steps (b) through (e) are repeated at least 60 times.
24. The method according to claim 12 , wherein the film optionally comprises one or more acid scavengers and optionally comprises one or more commercially available photoacid generators.
25. The method according to claim 12 , wherein the array comprises features of between 100 to 1000 nm in size.