Electrochemical deblocking solution for electrochemical oligomer synthesis on an electrode array
There is disclosed an electrochemical deblocking solution for use on an electrode microarray. There is further disclosed a method for electrochemical synthesis on an electrode array using the electrochemical deblocking solution. The solution and method are for removing acid-labile protecting groups for synthesis of oligonucleotides, peptides, small molecules, or polymers on a microarray of electrodes while substantially improving isolation of deblocking to active electrodes. The method comprises applying a voltage or a current to at least one electrode of an array of electrodes. The array of electrodes is covered by the electrochemical deblocking solution.
1. An electrochemical deblocking solution comprising:
an organic base including a lutidine, a benzoquinone and a hydroquinone;
tetraethylammonium p-toluenesulfonate as an organic salt; and
a solvent selected from the group consisting of an alcohol, acetonitrile and dichloromethane.
2. The electrochemical deblocking solution of claim 1 , where the solvent is between:
a lower limit of approximately 10% acetonitrile; and
an upper limit of approximately 99% acetonitrile.
3. The electrochemical deblocking solution of claim 1 , where the solvent has approximately 10% to 99% acetonitrile.
4. The electrochemical deblocking solution of claim 1 , where the solvent is between:
a lower limit of approximately 1% dichloromethane; and
an upper limit of approximately 99% dichloromethane.
5. The electrochemical deblocking solution of claim 1 , where the solvent is between:
a lower limit of approximately 1% isopropanol; and
an upper limit of approximately 99% isopropanol.
6. The electrochemical deblocking solution of claim 1 , where the lutidine is between:
a lower limit of approximately 0.01 mM dimethyl pyridine; and
an upper limit of approximately 200 mM dimethyl pyridine.
7. The electrochemical deblocking solution of claim 1 , where the benzoquinone is between:
a lower limit of approximately 0.1 mM; and
an upper limit of approximately 100 mM.
8. The electrochemical deblocking solution of claim 7 , where the hydroquinone is between:
a lower limit of approximately 0.1 mM; and
an upper limit of approximately 100 mM.
9. The electrochemical deblocking solution of claim 1 , where the tetraethylammonium p-toluenesulfonate is approximately is between:
a lower limit of approximately 0.1 mM; and
an upper limit of approximately 5 M.
10. The electrochemical deblocking solution of claim 9 , where the lutidine is between:
a lower limit of approximately 0.01 mM; and
an upper limit of approximately 200 mM.
11. The electrochemical deblocking solution of claim 9 , where the hydroquinone is between:
a lower limit of approximately 0.1 mM; and
an upper limit of approximately 100 mM.
12. The electrochemical deblocking solution of claim 9 , where the benzoquinone is between:
a lower limit of approximately 0.1 mM; and
an upper limit of approximately 100 mM.
13. The electrochemical deblocking solution of claim 1 , where the tetraethylammonium p-toluenesulfonate is dissolved in the solvent to form a first solution and the lutidine provides basicity to quench acidity of the tetraethylammonium p-toluenesulfonate in solution.
14. The electrochemical deblocking solution of claim 1 , where the tetraethylammonium p-toluenesulfonate is dissolved in the solvent to form a tetraethylammonium p-toluenesulfonate solution and the lutidine provides basicity to quench acidity of the tetraethylammonium p-toluenesulfonate solution.
15. A method of electrochemical deblocking an oligomer comprising the steps of:
covering an array of electrodes with a deblocking solution including:
lutidine, benzoquinone, hydroquinone and tetraethylammonium p-toluenesulfonate; and
one or more solvents selected from the group consisting of an alcohol, acetonitrile and dichloromethane; and
applying one or both a voltage and a current to at least one electrode of the array of electrodes.
16. The method of claim 15 , where lutidine is not bound to the array of electrodes.
17. The method of claim 15 , where the one or more solvents is between:
a lower limit of approximately 10% acetonitrile; and
an upper limit of approximately 99% acetonitrile.
18. The method of claim 15 , where the one or more solvents is between:
a lower limit of approximately 1% methanol; and
an upper limit of approximately 90% methanol.
19. The method of claim 15 , where the one or more solvents is between:
a lower limit of approximately 1% dichloromethane; and
an upper limit of approximately 99% dichloromethane.
20. A kit for electrochemical deblocking comprising:
an array of electrodes adapted to connect with one or both a voltage and a current source to apply one or both a voltage and a current to at least one electrode of the array of electrodes;
a deblocking solution including:
lutidine, benzoquinone, hydroquinone and tetraethylammonium p-toluenesulfonate; and
one or more solvents selected from the group consisting of an alcohol, acetonitrile and dichloromethane; and
instructions for one or both preparing the deblocking solution and applying one or both a voltage and a current to at least one electrode of the array of electrodes.