Polar dyes

An oligonucleotide conjugate comprising an oligonucleotide conjugated to a dye of Formula (VIII):

• wherein,
• z is 1,2 or 3;
• T is >C═O or >S(═O)2;
• Q is —OR71 or —NR72R73;
• U is —OR74 or —NR75R76;
• each R68 and R65 are the same or different and independently hydrogen, halogen, hydroxy, alkyl, aryl or —CH2As(═O)(OR6)(OR7) or —CH2As(OR6)2(OR7)2;
• each R66 and R67 are the same or different and independently hydrogen, halogen, hydroxy, alkyl or L-Rx;
• each R70 is the same or different and independently hydrogen, halogen, alkyl, —As(═O)(OR6)(OR7), —As(OR6)2(OR7)2 or L-Rx;
• R6 and R7 are the same or different and independently H, alkyl, aryl, or heteroaryl;
• or
• R6 and R7 are linked together to form a 5 or 6-member heterocycle comprising the arsenic and the two oxygen atoms to which R6 and R7 are attached, wherein —R6—R7— is —[C(R8)2]w— (w is 2 or 3), wherein each R8 is the same or different and independently hydrogen, hydroxy, cyano, —OC(O)-alkyl, —OC(O)-aryl, alkyl, aryl, alkylcarbonyl, arylcarbonyl, —CH2CN, —CH2SO2Me, —CH2SO2Ph, or two R8 of adjacent carbons together with the carbons to which they are attached form an aryl or heteroaryl, or two R8 of the same carbon form an oxo;
• each R71 and R74 are the same or different and independently is hydrogen, alkylcarbonyl or arylcarbonyl;
• each R72, R73, R75 and R76 are the same or different and independently hydrogen, alkyl or aryl;
• or
• R71 and R68, together with the carbons to which they are attached, form a 5 or 6 member heterocycle;
• or
• R74 and R65, together with the carbons to which they are attached, form a 5 or 6 member heterocycle;
• or
• R72 and R68, together with the carbons to which they are attached, form a 5 or 6 member heterocycle;
• or
• R73 and R66, together with the carbons to which they are attached, form a 5 or 6 member heterocycle;
• or
• R75 and R65, together with the carbons to which they are attached, form a 5 or 6 member heterocycle;
• or
• R76 and R67, together with the carbons to which they are attached, form a 5 or 6 member heterocycle;
• L is a single covalent bond or a covalent linkage having 1-30 non-hydrogen atoms selected from the group consisting of C, N, O and S and is composed of any combination of single, double, triple or aromatic carbon-carbon bonds, carbon-nitrogen bonds, nitrogen-nitrogen bonds, carbon-oxygen bonds and carbon-sulfur bonds;
• and
• Rx is an acrylamide, an activated ester of a carboxylic acid, an acyl azide, an acyl nitrile, an aldehyde, an alkyl halide, an amine, an anhydride, an aniline, an aryl halide, an aziridine, a boronate, a carboxylic acid, a diazoalkane, a haloacetamide, a halotriazine, a hydrazine, a hydrazide, an imido ester, an isocyanate, an isothiocyanate, a malemide, a phosphoramidite, a sulfonyl halide, a thiol group, a succiniminimidyl ester, a pentaflourophenyl ester, or an azidoperflourobenzamido group, and wherein Rx is reactively conjugated to the oligonucleotide,
• provided, at least one of R65, R66 R67, R68 and R71 is or comprises —As(═O)(OR6)(OR7) or —As(OR6)2(OR7)2.

A method of preparing an oligonucleotide in an automated synthesis, comprising:

• performing automated synthesis of oligonucleotide using phosphoramidite method by conjugating an oligonucleotide to a compound of Formula (VIII):
• wherein,
• z is 1, 2 or 3;
• T is >C═O or >S(═O)2;
• Q is —OR71 or —NR72R73;
• U is —OR74 or —NR75R76;
• each R68 and R65 are the same or different and independently hydrogen, halogen, hydroxy, alkyl, aryl or —CH2As(═O)(OR6)(OR7) or —CH2As(OR6)2(OR7)2;
• each R66 and R67 are the same or different and independently hydrogen, halogen, hydroxy, alkyl or L-Rx;
• each R7° is the same or different and independently hydrogen, halogen, alkyl, —As(═O)(OR6)(OR7), —As(OR6)2(OR7)2 or L-Rx;
• R6 and R7 are the same or different and independently H, alkyl, aryl, or heteroaryl;
• or
• R6 and R7 are linked together to form a 5 or 6-member heterocycle comprising the arsenic and the two oxygen atoms to which R6 and R7 are attached, wherein —R6—R7— is —[C(R8)2]w— (w is 2 or 3), wherein each R8 is the same or different and independently hydrogen, hydroxy, cyano, —OC(O)-alkyl, —OC(O)-aryl, alkyl, aryl, alkylcarbonyl, arylcarbonyl, —CH2CN, —CH2SO2Me, —CH2SO2Ph, or two R8 of adjacent carbons together with the carbons to which they are attached form an aryl or heteroaryl, or two R8 of the same carbon form an oxo;
• each R71 and R74 are the same or different and independently is hydrogen, alkylcarbonyl or arylcarbonyl;
• each R72, R73, R75 and R76 are the same or different and independently hydrogen, alkyl or aryl;
• or
• R71 and R68, together with the carbons to which they are attached, form a 5 or 6 member heterocycle;
• or
• R74 and R65, together with the carbons to which they are attached, form a 5 or 6 member heterocycle;
• or
• R72 and R68, together with the carbons to which they are attached, form a 5 or 6 member heterocycle;
• or
• R73 and R66, together with the carbons to which they are attached, form a 5 or 6 member heterocycle;
• or
• R75 and R65, together with the carbons to which they are attached, form a 5 or 6 member heterocycle;
• or
• R76 and R67, together with the carbons to which they are attached, form a 5 or 6 member heterocycle;
• L is a single covalent bond or a covalent linkage having 1-30 non-hydrogen atoms selected from the group consisting of C, N, O and S and is composed of any combination of single, double, triple or aromatic carbon-carbon bonds, carbon-nitrogen bonds, nitrogen-nitrogen bonds, carbon-oxygen bonds and carbon-sulfur bonds;
• provided, at least one of R65, R66 R67, R68 and R71 is or comprises —As(═O)(OR6)(OR7) or —As(OR6)2(OR7)2, and
• Rx is a phosphoramidite, to provide a dye-labeled oligonucleotide;
• deprotecting —As(═O)(OR6)(OR7) or —As(OR6)2(OR7)2 of the dye-labeled oligonucleotide to provide a dye-labeled oligonucleotide having negatively charged polar group selected from —AsO32− or —AsO3H−;
• and
• isolating the dye-labeled oligonucleotide having negatively charged polar group selected from —AsO32− or —AsO3H−.