Monomers and oligonucleotides comprising cycloaddition adduct(s)

1. A compound of formula II, or a pharmaceutically acceptable salt thereof:

A and B are independently for each occurrence hydrogen, protecting group, optionally substituted aliphatic, optionally substituted aryl, optionally substituted heteroaryl, polyethyleneglycol (PEG), a phosphate, a diphosphate, a triphosphate, a phosphonate, a phosphonothioate, a phosphonodithioate, a phosphorothioate, a phosphorothiolate, a phosphorodithioate, a phosphorothiolothionate, a phosphodiester, a phosphotriester, a phosphoramidite, a solid support, —P(Z 1 )(Z 2 )—O-nucleoside, or —P(Z 1 )(Z 2 )—O-oligonucleotide; wherein Z 1 and Z 2 are each independently for each occurrence O, S or optionally substituted alkyl;

J 1 and J 2 are independently O, S, NR N , optionally substituted alkyl, OC(O)NH, NHC(O)O, C(O)NH, NHC(O), OC(O), C(O)O, OC(O)O, NHC(O)NH, NHC(S)NH, OC(S)NH, OP(N(R P ) 2 )O, or OP(N(R P ) 2 );

is a trisubstituted cyclic group selected from the group consisting of pyrrolidinyl, pyrazolinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, piperidinyl, piperazinyl, [1,3]dioxolane, oxazolidinyl, isoxazolidinyl, morpholinyl, thiazolidinyl, isothiazolidinyl, quinoxalinyl, pyridazinonyl, tetrahydrofuryl and decalin; or

 is a trisubstituted acyclic group containing a serinol backbone or diethanolamine backbone, wherein LIGAND is attached to the

 via the “N” atom in the serinol or diethanolamine backbone, and A and B are attached to the

 via each “O” atom in the serinol or diethanolamine backbone;

Q is independently for each occurrence

X 1 is O, S, CF 2 , or CH 2 ;

Y 1 , Y 2 and Y 3 are each independent CR P , N, O, or S;

W 1 is CH or N;

R 100 , R 200 , R 300 and R 400 are each independently hydrogen, halogen, OR N , CR P 2 , acyl, phosphonyl, sulfonyl; or alternatively, R 100 and R 200 or R 300 and R 400 are taken together to form an aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, heterocycloalkyl, or substituted heterocycloalkyl;

R N is independently for each occurrence H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted aralkyl, optionally substituted heteroaryl or an amino protecting group;

R P is independently for each occurrence H, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted cycloalkyl or optionally substituted heteroaryl;

L 10 and L 11 are independently absent or a linker; and

LIGAND is a ligand selected from the group consisting of thyrotropin, melanotropin, lectin, glycoprotein, surfactant protein A, Mucin carbohydrate, multivalent lactose, galactose, multivalent galactose, N-acetyl-galactosamine, multivalent N-acetyl-galactosamine, N-acetyl-glucosamine, multivalent N-acetyl-glucosamine, multivalent mannose, multivalent fucose, glycosylated polyaminoacids, transferrin, bisphosphonate, polyglutamate, polyaspartate, a lipid, cholesterol, a steroid, bile acid, folate, vitamin B12, biotin, an RGD peptide, an RGD peptide mimetic, and an aptamer,

wherein, in each occurrence, the substituent group on the substituted aliphatic, substituted aryl, substituted heteroaryl, substituted alkyl, substituted cycloalkyl, substituted heterocycloalkyl, substituted alkenyl, substituted alkynyl, or substituted aralkyl is independently selected from the group consisting of halo, alkyl, alkenyl, alkynyl, aryl, heterocyclyl, thiol, alkylthio, arylthio, alkylthioalkyl, arylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl, arylsulfonylalkyl, alkoxy, aryloxy, aralkoxy, aminocarbonyl, alkylamino carbonyl, arylaminocarbonyl, alkoxycarbonyl, aryloxycarbonyl, haloalkyl, amino, trifluoromethyl, cyano, nitro, alkylamino, arylamino, alkylaminoalkyl, arylaminoalkyl, aminoalkylamino, hydroxy, alkoxyalkyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, acyl, aralkoxycarbonyl, carboxylic acid, sulfonic acid, sulfonyl, phosphonic acid, aryl, heteroaryl, heterocyclic, and aliphatic.

2. The compound of claim 1 , wherein the ligand is selected from the group consisting of:

3. The compound of claim 1 , wherein L 10 and L 11 are independently a each linker represented by structure

-[P-Q 1 -R] q -T-,

wherein:

P, R and T are each independently for each occurrence either absent, or CO, NH, O, S, S—S, OC(O), NHC(O), CH 2 , CH 2 NH, CH 2 O; NHCH(R a )C(O), —C(O)—CH(R a )—NH—, —C(O)-(optionally substituted alkyl)-NH—, CH═N—O,

 acetal, ketal,

 Q 1 is independently for each occurrence either absent, or —(CH 2 ) n —, —C(R 100 )(R 200 )NCH 2 ) n —, —(CH 2 ) n C(R 100 )(R 200 )—, —(CH 2 CH 2 O) m CH 2 CH 2 —, or —(CH 2 CH 2 O) m CH 2 CH 2 NH—;

R a is H or an amino acid side chain;

R 100 and R 200 are each independently for each occurrence H, CH 3 , OH, SH or N(R X ) 2 ;

R X is independently for each occurrence H, methyl, ethyl, propyl, isopropyl, butyl or benzyl;

q is independently for each occurrence 0-20;

n is independently for each occurrence 1-20; and

m is independently for each occurrence 0-50,

wherein, in each occurrence, the substituent group on the substituted alkyl is independently selected from the group consisting of halo, alkyl, alkenyl, alkynyl, aryl, heterocyclyl, thiol, alkylthio, arylthio, alkylthioalkyl, arylthioalkyl, alkylsulfonyl, alkylsulfonylalkyl, arylsulfonylalkyl, alkoxy, aryloxy, aralkoxy, aminocarbonyl, alkylamino carbonyl, arylaminocarbonyl, alkoxycarbonyl, aryloxycarbonyl, haloalkyl, amino, trifluoromethyl, cyano, nitro, alkylamino, arylamino, alkylaminoalkyl, arylaminoalkyl, aminoalkylamino, hydroxy, alkoxyalkyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, acyl, aralkoxycarbonyl, carboxylic acid, sulfonic acid, sulfonyl, phosphonic acid, aryl, heteroaryl, heterocyclic, and aliphatic.

4. The compound of claim 1 , wherein either one or both of A and B is independently —P(Z 1 )(Z 2 )—O-oligonucleotide.

5. The compound of claim 4 , wherein the oligonucleotide is a single-stranded oligonucleotide.

6. The compound of claim 5 , wherein the single-stranded oligonucleotide is a single-stranded siRNA.

7. The compound of claim 4 , wherein the oligonucleotide is a double-stranded oligonucleotide.

8. The compound of claim 7 , wherein the double-stranded oligonucleotide is a double-stranded siRNA.