Silyl monomers capable of multimerizing in an aqueous solution, and methods of using same

Abstract

Described herein are silyl monomers capable of forming a biologically useful multimer when in contact with one, two, three or more other monomers in an aqueous media. Such multimer forming associations of monomers may be promoted by the proximal binding of the monomers to their target biomolecule(s). In one aspect, such monomers may be capable of binding to another monomer in an aqueous media (e.g. in vivo) to form a multimer, (e.g. a dimer). Contemplated monomers may include a ligand moiety, a linker element, and a connector element that joins the ligand moiety and the linker element. In an aqueous media, such contemplated monomers may join together via each linker element and may thus be capable of modulating one or more biomolecules substantially simultaneously, e.g., modulate two or more binding domains on a protein or on different proteins.

What is claimed is: 
     
         1 . A therapeutic multimer compound formed from the multimerization in an aqueous media of the first monomer represented by:
   X 1 —Y 1 —Z 1   (Formula I)
   and pharmaceutically acceptable salts, stereoisomers, metabolites and hydrates thereof, and the second monomer represented by:
   X 2 —Y 2 —Z 2   (Formula II)
 
   and pharmaceutically acceptable salts, stereoisomers, metabolites and hydrates thereof.   
     
     
         2 . The therapeutic multimer compound of  claim 1 , wherein
 X 1  is a first ligand moiety capable of binding to and modulating a first target biomolecule;   Y 1  is absent or is a connector moiety covalently bound to X 1  and Z 1 ;   X 2  is a second ligand moiety capable of binding to and modulating a second target biomolecule;   Y 2  is absent or is a connector moiety covalently bound to X 2  and Z 2 ;   Z 1  and Z 2 , independently, for each occurrence, are selected from the group consisting of:   
       
         
           
           
               
               
           
         
         
           wherein
 R W  is selected from the group consisting of a bond, —C 1-4 alkyl-, —O—C 1-4 alkyl-, —N(R a )—C 1-4 alkyl-, —C 1-4 alkyl-C(O)—, —C(O)C 1-4 alkyl-, —C 1-4 alkyl-O—C(O)—, —C(O)—O—C 1-4 alkyl-, —NR a —C(O)—, —C 2-6 alkenyl-, —C 2-6 alkynyl-, —C 3-6 cycloalkyl-, -phenyl-, -heteroaryl-, and -heterocyclic-; wherein C 1-4 alkyl, R a , R b , C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl and heteroaryl may be optionally substituted by one, two, three or more substituents selected from the group consisting of C 1-4 alkyl, C 1-4 alkoxy, —C(O)C 1-4 alkyl, —C(O)—O—C 1-4 alkyl, —C(O)—NR a R b , halogen, cyano, hydroxyl, cycloalkyl, heterocyclic, phenyl, heteroaryl, R a  and R b , wherein the cycloalkyl, heterocyclic, phenyl, or heteroaryl moiety is optionally substituted with one, two, three or more substituents selected from halogen, amino, cyano, hydroxyl, C 1-6 alkyl, phenyl, heteroaryl, and amino; 
 W 1 , independently for each occurrence, is (a) absent; or (b) selected from the group consisting of —C 1-4 alkyl-, —O—C 1-4 alkyl-, —C 1-4 alkyl-C(O)—, —C(O)—C 1-4 alkyl-, —N(R a )—C 1-4 alkyl-, —C 1-4 alkyl-O—C(O)—, —C(O)—O—C 1-4 alkyl-, —NR a —C(O)—, —C 2-6 alkenyl-, —C 2-6 alkynyl-, —C 3-6 cycloalkyl-, -phenyl-, -heteroaryl-, and heterocyclic; wherein C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, R′, phenyl, heterocyclic, and heteroaryl are optionally substituted independently, for each occurrence, with one, two, three or more substituents selected from the group consisting of C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 alkoxy, —C(O)C 1-6 alkyl, —C(O)—O—C 1-4 alkyl, cycloalkyl, heterocyclic, phenyl, heteroaryl, halogen, hydroxyl, nitro sulfoxide, sulfone, sulfonamide and cyano, wherein the cycloalkyl, heterocyclic, phenyl, or heteroaryl moiety is optionally substituted with one, two, three or more substituents selected from halogen, amino, cyano, hydroxyl, C 1-6 alkyl, phenyl, heteroaryl, and amino; 
 R′ is independently selected, for each occurrence, from the group consisting of hydrogen, substituted or unsubstituted aliphatic, and substituted or unsubstituted heteroaliphatic; 
 Q 1  is independently selected, for each occurrence, from the group consisting of —NHR′, —N(R′) 2 , —NR a R b , —O—Si(R′) 3 , —O—SiR a R b R′, —SH, —OH, —O—C 1-6 alkyl, —S—C 1-6 alkyl, —O-aryl, —S-aryl, heteroaryl, —O-heteroaryl, —S-heteroaryl, halogen and —O—C 1-6 alkyl-NR a R b ; 
 R a  and R b  are independently selected, for each occurrence, from the group consisting of hydrogen, C 1-4 alkyl, —O—C 1-4 alkyl and —NH—C 1-4 alkyl; wherein C 1-4 alkyl may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo and hydroxyl; or 
 R a  and R b , together with the nitrogen to which they are attached, may form a 4-7 membered heterocyclic ring, which may have one or more additional heteroatoms selected from O, S, or N; wherein the 4-7 membered heterocyclic ring may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo, amino and hydroxyl; 
 R 1  and R 2  are selected independently, for each occurrence, from the group consisting of —OH, C 1-6 alkyl, —O—C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, —C 1-6 alkyl-NR a R b , phenyl and heteroaryl; wherein C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, R a , R b , phenyl and heteroaryl, independently selected, for each occurrence, may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, hydroxyl, amino, C 1-6 alkyl, heteroaryl, and phenyl; or R 1  and R 2 , together with the silicon to which they are attached, may form a 5-8 membered heterocyclic ring, which may have one or more additional heteroatoms selected from O, S, or N; wherein the 5-8 membered heterocyclic ring may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo, amino and hydroxyl; 
 BB, independently for each occurrence, is a 4-7-membered cycloalkyl, heterocyclic, aryl, or heteroaryl moiety, wherein the cycloalkyl, heterocyclic, aryl, or heteroaryl moiety is optionally substituted with one, two, three or more groups represented by R BB ; wherein R 1 , independently for each occurrence, may be optionally bonded to BB; 
 each R BB  is independently selected, for each occurrence, from the group consisting of hydrogen, halogen, nitro, cyano, hydroxyl, amino, thio, —COOH, —CONHR′, substituted or unsubstituted aliphatic, substituted or unsubstituted heteroaliphatic, —C 1-4 alkyl, —O—C 1-4 alkyl, —N(R a )—C 1-4 alkyl, —C(O)C 1-4 alkyl, —C(O)—O—C 1-4 alkyl, —C(O)—NR a R b , —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-6 cycloalkyl, heterocyclic, phenyl, phenoxy, heteroaryl, —C 1-4 alkylene-phenyl, —C 1-4 alkylene-heteroaryl, —C 1-4 alkylene-heterocyclyl, —C 2-6 alkenylene-phenyl, —C 2-6 alkenylene-heteroaryl, —C 2-6 alkenylene-heterocyclyl, —C 2-6 alkynyl-phenyl, —C 2-6 alkynyl-heteroaryl, —C 2-6 alkynyl-heterocyclyl; wherein C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, phenoxy, heterocyclyl, and heteroaryl are optionally substituted by one, two, three or more substituents selected from the group consisting of C 1-4 alkyl, C 1-4 alkoxy, —C(O)C 1-4 alkyl, —C(O)—O—C 1-4 alkyl, —C(O)—NR a R b , halogen, cyano, hydroxyl, cycloalkyl, heterocyclic, phenyl, or heteroaryl; or two R BB  together with the atoms to which they are attached form a fused 5- or 6-membered cycloalkyl or heterocyclic bicyclic ring system; and 
 
         
       
       
         
           
           
               
               
           
         
         
           wherein
 Q 2A  may be selected from the group consisting of a bond, —O—C 1-6 alkyl-, —N(R′)—C 1-6 alkyl-, and —S—C 1-6 alkyl-; 
 W 1 , independently for each occurrence, is (a) absent; or (b) selected from the group consisting of —C 1-4 alkyl-, —O—C 1-4 alkyl-, —N(Ra)—C 1-4 alkyl-, —C 1-4 alkyl-C(O)—, —C(O)C 1-4 alkyl-, —C 1-4 alkyl-O—C(O)—, —C(O)—O—C 1-4 alkyl-, —NR′—C(O)—, —C 2-6 alkenyl-, —C 2-6 alkynyl-, —C 3-6 cycloalkyl-, -phenyl-, and -heteroaryl-; wherein C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, R′, R a  phenyl and heteroaryl may be optionally substituted independently, for each occurrence, with one, two, three or more substituents selected from the group consisting of C 1-4 alkyl, C 1-4 alkoxy, —C(O)C 1-6 alkyl, —C(O)—O—C 1-4 alkyl, halogen, hydroxyl, nitro, carbamate, carbonate and cyano; 
 W 1A , independently for each occurrence, is (a) absent; or (b) selected from the group consisting of —C 1-4 alkyl-, —C 1-4 alkyl-O—, —C 1-4 alkyl-N(R a )—, —C 1-4 alkyl-C(O)—, —C(O)C 1-4 alkyl-, —C 1-4 alkyl-O—C(O)—, —C(O)—O—C 1-4 alkyl-, —C(O)—NR′—, —C 2-6 alkenyl-, —C 2-6 alkynyl-, —C 3-6 cycloalkyl-, -phenyl-, and -heteroaryl-; wherein C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, R′, R a  phenyl and heteroaryl may be optionally substituted independently, for each occurrence, with one, two, three or more substituents selected from the group consisting of C 1-4 alkyl, C 1-4 alkoxy, —C(O)C 1-6 alkyl, —C(O)—O—C 1-4 alkyl, halogen, hydroxyl, nitro, carbamate, carbonate and cyano; 
 R′ is independently selected, for each occurrence, from the group consisting of hydrogen, substituted or unsubstituted aliphatic, and substituted or unsubstituted heteroaliphatic; 
 Q 1  and Q 1A  are independently selected, for each occurrence, from the group consisting of —NHR′, —N(R′) 2 , —NR a R b , —O—Si(R′) 3 , —O—SiR a R b R′, —SH, —OH, —O—C 1-6 alkyl, —S—C 1-6 alkyl, —O-aryl, —S-aryl, heteroaryl, —O-heteroaryl, —S-heteroaryl, halogen and —O—C 1-6 alkyl-NR a R b ; 
 R a  and R b  are independently selected, for each occurrence, from the group consisting of hydrogen and C 1-4 alkyl; wherein C 1-4 alkyl may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo and hydroxyl; or 
 R a  and R b , together with the nitrogen to which they are attached, may form a 4-7 membered heterocyclic ring, which may have an additional heteroatom selected from O, S, or N; wherein the 4-7 membered heterocyclic ring may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo and hydroxyl; 
 R 1  and R 2  are selected independently, for each occurrence, from the group consisting of —OH, C 1-6 alkyl, —O—C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, —C 1-6 alkyl-NR a R b , phenyl and heteroaryl; wherein C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, R a , R b , phenyl and heteroaryl, independently selected, for each occurrence, may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, hydroxyl, amino, C 1-6 alkyl, heteroaryl, and phenyl; or R 1  and R 2 , together with the silicon to which they are attached, may form a 5-8 membered heterocyclic ring, which may have one or more additional heteroatoms selected from O, S, or N; wherein the 5-8 membered heterocyclic ring may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo, amino and hydroxyl; 
 W 2A  is CR W2A , 
 R W2A  is selected from the group consisting of hydrogen, C 1-4 alkyl, —O—C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl and heteroaryl; wherein C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl and heteroaryl are optionally substituted independently, for each occurrence, with one, two, three or more substituents selected from the group consisting of halogen, hydroxyl and cyano; 
 BB, independently for each occurrence, is a 4-7-membered cycloalkyl, heterocyclic, aryl, or heteroaryl moiety; wherein the cycloalkyl, heterocyclic, aryl, or heteroaryl moiety is optionally substituted with one, two, three or more groups represented by R BB ; wherein R 1 , independently for each occurrence, may be optionally bonded to BB; 
 each R BB  is independently selected, for each occurrence, from the group consisting of hydrogen, halogen, nitro, cyano, hydroxyl, amino, thio, —COOH, —CONHR′, substituted or unsubstituted aliphatic, substituted or unsubstituted heteroaliphatic, —C 1-4 alkyl, —O—C 1-4 alkyl, —N(R a )—C 1-4 alkyl, —C(O)C 1-4 alkyl, —C(O)—O—C 1-4 alkyl, —C(O)—NR a R b , —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-6 cycloalkyl, heterocyclic, phenyl, phenoxy, heteroaryl, —C 1-4 alkylene-phenyl, —C 1-4 alkylene-heteroaryl, —C 1-4 alkylene-heterocyclyl, —C 2-6 alkenylene-phenyl, —C 2-6 alkenylene-heteroaryl, —C 2-6 alkenylene-heterocyclyl, —C 2-6 alkynyl-phenyl, —C 2-6 alkynyl-heteroaryl, —C 2-6 alkynyl-heterocyclyl; wherein C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, phenoxy, heterocyclyl, and heteroaryl are optionally substituted by one, two, three or more substituents selected from the group consisting of C 1-4 alkyl, C 1-4 alkoxy, —C(O)C 1-4 alkyl, —C(O)—O—C 1-4 alkyl, —C(O)—NR a R b , halogen, cyano, hydroxyl, cycloalkyl, heterocyclic, phenyl, or heteroaryl; or two R BB  together with the atoms to which they are attached form a fused 5- or 6-membered cycloalkyl or heterocyclic bicyclic ring system. 
 
         
       
     
     
         3 . The therapeutic multimer compound of  claim 1 , wherein
 X 1  is a first ligand moiety capable of binding to and modulating a first target biomolecule;   Y 1  is absent or is a connector moiety covalently bound to X 1  and Z 1 ;   Z 1  is selected from the group consisting of:   
       
         
           
           
               
               
           
         
         
           wherein 
           A 1  is (a) absent; or (b) selected from the group consisting of acyl, substituted or unsubstituted aliphatic, and substituted or unsubstituted heteroaliphatic; 
           A 2 , independently for each occurrence, is (a) absent; or (b) selected from the group consisting of —N—, acyl, substituted or unsubstituted aliphatic, and substituted or unsubstituted heteroaliphatic, provided that at least one of A 1  and A 2  is present; or 
           A 1  and A 2 , together with the atoms to which they are attached, form a 4-8 membered cycloalkyl or heterocyclic ring; 
           A 3  is selected from the group consisting of —NHR′, —SH, and —OH; 
           W 2  is selected from the group consisting of CR′ or N; 
           m is 1-6; 
              represents a single or double bond; and 
           R X  is (a) absent; or (b) selected from the group consisting of hydrogen, substituted or unsubstituted aliphatic, and substituted or unsubstituted heteroaliphatic; 
           Q 2  is (a) absent; or (b) selected from the group consisting of a substituted or unsubstituted aliphatic and a substituted or unsubstituted heteroaliphatic moiety; or 
           R X  and Q 2  together with the atoms to which they are attached form a 4-, 5-, 6-, 7-, or 8-membered cycloalkyl or heterocyclic ring; 
           Q 3  is selected from the group consisting of a substituted or unsubstituted aliphatic and a substituted or unsubstituted heteroaliphatic moiety; 
           W 1 , independently for each occurrence, is (a) absent; or (b) selected from the group consisting of —C 1-4 alkyl-, —O—C 1-4 alkyl-, —C 1-4 alkyl-C(O)—, —C(O)—C 1-4 alkyl-, —N(R a )—C 1-4 alkyl-, —C 1-4 alkyl-O—C(O)—, —C(O)—O—C 1-4 alkyl-, —NR a —C(O)—, —C 2-6 alkenyl-, —C 2-6 alkynyl-, —C 3-6 cycloalkyl-, -phenyl-, -heteroaryl-, and heterocyclic; wherein C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, R′, phenyl, heterocyclic, and heteroaryl are optionally substituted independently, for each occurrence, with one, two, three or more substituents selected from the group consisting of C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 alkoxy, —C(O)C 1-6 alkyl, —C(O)—O—C 1-4 alkyl, cycloalkyl, heterocyclic, phenyl, heteroaryl, halogen, hydroxyl, nitro sulfoxide, sulfone, sulfonamide and cyano, wherein the cycloalkyl, heterocyclic, phenyl, or heteroaryl moiety is optionally substituted with one, two, three or more substituents selected from halogen, amino, cyano, hydroxyl, C 1-6 alkyl, phenyl, heteroaryl, and amino; 
           R′ is independently selected, for each occurrence, from the group consisting of hydrogen, substituted or unsubstituted aliphatic, and substituted or unsubstituted heteroaliphatic; 
           Q 1  is independently selected, for each occurrence, from the group consisting of —NHR′, —N(R′) 2 , —NR a R b , —O—Si(R′) 3 , —O—SiR a R b R′, —SH, —OH, —O—C 1-6 alkyl, —S—C 1-6 alkyl, —O-aryl, —S-aryl, heteroaryl, —O-heteroaryl, —S-heteroaryl, halogen and —O—C 1-6 alkyl-NR a R b ; 
           R a  and R b  are independently selected, for each occurrence, from the group consisting of hydrogen and C 1-4 alkyl; wherein C 1-4 alkyl may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo and hydroxyl; or 
           R a  and R b , together with the nitrogen to which they are attached, may form a 4-7 membered heterocyclic ring, which may have an additional heteroatom selected from O, S, or N; wherein the 4-7 membered heterocyclic ring may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo and hydroxyl; 
           R 1  and R 2  are selected independently, for each occurrence, from the group consisting of —OH, C 1-6 alkyl, —O—C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, —C 1-6 alkyl-NR a R b , phenyl and heteroaryl; wherein C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, R a , R b , phenyl and heteroaryl, independently selected, for each occurrence, may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, hydroxyl, amino, C 1-6 alkyl, heteroaryl, and phenyl; or R 1  and R 2 , together with the silicon to which they are attached, may form a 5-8 membered heterocyclic ring, which may have one or more additional heteroatoms selected from O, S, or N; wherein the 5-8 membered heterocyclic ring may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo, amino and hydroxyl; 
           BB, independently for each occurrence, is a 5- or 6-membered cycloalkyl, heterocyclic, aryl, or heteroaryl moiety, wherein the cycloalkyl, heterocyclic, aryl, or heteroaryl moiety is optionally substituted with one, two, three or more groups represented by R BB ; wherein R 1 , independently for each occurrence, may be optionally bonded to BB; 
           each R BB  is independently selected, for each occurrence, from the group consisting of hydrogen, halogen, nitro, cyano, hydroxyl, amino, thio, —COOH, —CONHR′, substituted or unsubstituted aliphatic, substituted or unsubstituted heteroaliphatic, —C 1-4 alkyl, —O—C 1-4 alkyl, —N(R a )—C 1-4 alkyl, —C(O)C 1-4 alkyl, —C(O)—O—C 1-4 alkyl, —C(O)—NR a R b , —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-6 cycloalkyl, heterocyclic, phenyl, phenoxy, heteroaryl, —C 1-4 alkylene-phenyl, —C 1-4 alkylene-heteroaryl, —C 1-4 alkylene-heterocyclyl, —C 2-6 alkenylene-phenyl, —C 2-6 alkenylene-heteroaryl, —C 2-6 alkenylene-heterocyclyl, —C 2-6 alkynyl-phenyl, —C 2-6 alkynyl-heteroaryl, —C 2-6 alkynyl-heterocyclyl; wherein C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, phenoxy, heterocyclyl, and heteroaryl are optionally substituted by one, two, three or more substituents selected from the group consisting of C 1-4 alkyl, C 1-4 alkoxy, —C(O)C 1-4 alkyl, —C(O)—O—C 1-4 alkyl, —C(O)—NR a R b , halogen, cyano, hydroxyl, cycloalkyl, heterocyclic, phenyl, or heteroaryl; or two R BB  together with the atoms to which they are attached form a fused 5- or 6-membered cycloalkyl or heterocyclic bicyclic ring system; and 
         
       
       
         
           
           
               
               
           
         
         wherein
 A 1 , independently for each occurrence, is (a) absent; or (b) selected from the group consisting of acyl, substituted or unsubstituted aliphatic, and substituted or unsubstituted heteroaliphatic; 
 A 3 , independently for each occurrence, is selected from the group consisting of —NHR′, —SH, and —OH; 
 W 1 , independently for each occurrence, is (a) absent; or (b) selected from the group consisting of —C 1-4 alkyl-, —O—C 1-4 alkyl-, —C 1-4 alkyl-C(O)—, —C(O)—C 1-4 alkyl-, —N(R a )—C 1-4 alkyl-, —C 1-4 alkyl-O—C(O)—, —C(O)—O—C 1-4 alkyl-, —NR a —C(O)—, —C 2-6 alkenyl-, —C 2-6 alkynyl-, —C 3-6 cycloalkyl-, -phenyl-, -heteroaryl-, and heterocyclic; wherein C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, R′, phenyl, heterocyclic, and heteroaryl are optionally substituted independently, for each occurrence, with one, two, three or more substituents selected from the group consisting of C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 alkoxy, —C(O)C 1-6 alkyl, —C(O)—O—C 1-4 alkyl, cycloalkyl, heterocyclic, phenyl, heteroaryl, halogen, hydroxyl, nitro sulfoxide, sulfone, sulfonamide and cyano, wherein the cycloalkyl, heterocyclic, phenyl, or heteroaryl moiety is optionally substituted with one, two, three or more substituents selected from halogen, amino, cyano, hydroxyl, C 1-6 alkyl, phenyl, heteroaryl, and amino; 
 R′ is independently selected, for each occurrence, from the group consisting of hydrogen, substituted or unsubstituted aliphatic, and substituted or unsubstituted heteroaliphatic; 
 Q 1  is independently selected, for each occurrence, from the group consisting of —NHR′, —N(R′) 2 , —NR a R b , —O—Si(R′) 3 , —O—SiR a R b R′, —SH, —OH, —O—C 1-6 alkyl, —S—C 1-6 alkyl, —O-aryl, —S-aryl, heteroaryl, —O-heteroaryl, —S-heteroaryl, halogen and —O—C 1-6 alkyl-NR a R b ; 
 R a  and R b  are independently selected, for each occurrence, from the group consisting of hydrogen and C 1-4 alkyl; wherein C 1-4 alkyl may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo and hydroxyl; or 
 R a  and R b , together with the nitrogen to which they are attached, may form a 4-7 membered heterocyclic ring, which may have an additional heteroatom selected from O, S, or N; wherein the 4-7 membered heterocyclic ring may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo and hydroxyl; 
 R 1  and R 2  are selected independently, for each occurrence, from the group consisting of —OH, C 1-6 alkyl, —O—C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, —C 1-6 alkyl-NR a R b , phenyl and heteroaryl; wherein C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, R a , R b , phenyl and heteroaryl, independently selected, for each occurrence, may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, hydroxyl, amino, C 1-6 alkyl, heteroaryl, and phenyl; or R 1  and R 2 , together with the silicon to which they are attached, may form a 5-8 membered heterocyclic ring, which may have one or more additional heteroatoms selected from O, S, or N; wherein the 5-8 membered heterocyclic ring may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo, amino and hydroxyl; 
 BB, independently for each occurrence, is a 5- or 6-membered cycloalkyl, heterocyclic, aryl, or heteroaryl moiety, wherein the cycloalkyl, heterocyclic, aryl, or heteroaryl moiety is optionally substituted with one, two, three or more groups represented by R BB ; wherein R 1 , independently for each occurrence, may be optionally bonded to BB; 
 each R BB  is independently selected, for each occurrence, from the group consisting of hydrogen, halogen, nitro, cyano, hydroxyl, amino, thio, —COOH, —CONHR′, substituted or unsubstituted aliphatic, substituted or unsubstituted heteroaliphatic, —C 1-4 alkyl, —O—C 1-4 alkyl, —N(R a )—C 1-4 alkyl, —C(O)C 1-4 alkyl, —C(O)—O—C 1-4 alkyl, —C(O)—NR a R b , —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-6 cycloalkyl, heterocyclic, phenyl, phenoxy, heteroaryl, —C 1-4 alkylene-phenyl, —C 1-4 alkylene-heteroaryl, —C 1-4 alkylene-heterocyclyl, —C 2-6 alkenylene-phenyl, —C 2-6 alkenylene-heteroaryl, —C 2-6 alkenylene-heterocyclyl, —C 2-6 alkynyl-phenyl, —C 2-6 alkynyl-heteroaryl, —C 2-6 alkynyl-heterocyclyl; wherein C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, phenoxy, heterocyclyl, and heteroaryl are optionally substituted by one, two, three or more substituents selected from the group consisting of C 1-4 alkyl, C 1-4 alkoxy, —C(O)C 1-4 alkyl, —C(O)—O—C 1-4 alkyl, —C(O)—NR a R b , halogen, cyano, hydroxyl, cycloalkyl, heterocyclic, phenyl, or heteroaryl; or two R BB  together with the atoms to which they are attached form a fused 5- or 6-membered cycloalkyl or heterocyclic bicyclic ring system; and 
 
       
       
         
           
           
               
               
           
         
         
           wherein 
           A 3 , independently for each occurrence, is selected from the group consisting of —NHR′, —SH, and —OH; 
           R 3  and R 4  are independently selected from the group consisting of H, C 1-4 alkyl and phenyl; or R 3  and R 4  taken together form a 3-6 membered ring; 
           R 5  and R 6  are independently selected from the group consisting of H, C 1-4 alkyl; wherein C 1-4 alkyl is optionally substituted independently, for each occurrence, with one, two, three or more substituents selected from the group consisting of hydroxyl, amino, halo, thio, C 1-4 alkoxy, halogen, —OH, —CN, —COOH, and —C(O)—NHR″; or R 5  and R 6 , taken together form phenyl or a 4-6 membered heterocycle; 
           R″ is selected from the group consisting of H and C 1-4 alkyl; 
           W 1 , independently for each occurrence, is (a) absent; or (b) selected from the group consisting of —C 1-4 alkyl-, —O—C 1-4 alkyl-, —C 1-4 alkyl-C(O)—, —C(O)—C 1-4 alkyl-, —N(Ra)—C 1-4 alkyl-, —C 1-4 alkyl-O—C(O)—, —C(O)—O—C 1-4 alkyl-, —NR a —C(O)—, —C 2-6 alkenyl-, —C 2-6 alkynyl-, —C 3-6 cycloalkyl-, -phenyl-, -heteroaryl-, and heterocyclic; wherein C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, R′, phenyl, heterocyclic, and heteroaryl are optionally substituted independently, for each occurrence, with one, two, three or more substituents selected from the group consisting of C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 alkoxy, —C(O)C 1 -6alkyl, —C(O)—O—C 1-4 alkyl, cycloalkyl, heterocyclic, phenyl, heteroaryl, halogen, hydroxyl, nitro sulfoxide, sulfone, sulfonamide and cyano, wherein the cycloalkyl, heterocyclic, phenyl, or heteroaryl moiety is optionally substituted with one, two, three or more substituents selected from halogen, amino, cyano, hydroxyl, C 1-6 alkyl, phenyl, heteroaryl, and amino; 
           R′ is independently selected, for each occurrence, from the group consisting of hydrogen, substituted or unsubstituted aliphatic, and substituted or unsubstituted heteroaliphatic; 
           Q 1  is independently selected, for each occurrence, from the group consisting of —NHR′, —N(R′) 2 , —NR a R b , —O—Si(R′) 3 , —O—SiR a R b R′, —SH, —OH, —O—C 1-6 alkyl, —S—C 1-6 alkyl, —O-aryl, —S-aryl, heteroaryl, —O-heteroaryl, —S-heteroaryl, halogen and —O—C 1-6 alkyl-NR a R b ; 
           R a  and R b  are independently selected, for each occurrence, from the group consisting of hydrogen and C 1-4 alkyl; wherein C 1-4 alkyl may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo and hydroxyl; or 
           R a  and R b , together with the nitrogen to which they are attached, may form a 4-7 membered heterocyclic ring, which may have an additional heteroatom selected from O, S, or N; wherein the 4-7 membered heterocyclic ring may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo and hydroxyl; 
           R 1  and R 2  are selected independently, for each occurrence, from the group consisting of —OH, C 1-6 alkyl, —O—C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, —C 1-6 alkyl-NR a R b , phenyl and heteroaryl; wherein C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, R a , R b , phenyl and heteroaryl, independently selected, for each occurrence, may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, hydroxyl, amino, C 1-6 alkyl, heteroaryl, and phenyl; or R 1  and R 2 , together with the silicon to which they are attached, may form a 5-8 membered heterocyclic ring, which may have one or more additional heteroatoms selected from O, S, or N; wherein the 5-8 membered heterocyclic ring may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo, amino and hydroxyl; 
           AR is a fused phenyl or 4-7 membered aromatic or partially aromatic heterocyclic ring, wherein AR is optionally substituted by oxo, C 1-4 alkyl optionally substituted by hydroxyl, amino, halo, or thio; C 1-4 alkoxy; —S—C 1-4 alkyl; halogen; —OH; —CN; —COOH; —CONHR′; wherein the two hydroxyl moieties are ortho to each other; 
           the carbons of the phenyl ring may be independently, for each occurrence, optionally replaced by one or two nitrogens; and 
         
       
       
         
           
           
               
               
           
         
         wherein
 W 3 , independently for each occurrence, is selected from the group consisting of N and CR W3    
 R W3 , independently for each occurrence, is selected from the group consisting of hydrogen, C 1-4 alkyl, —O—C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl and heteroaryl; wherein C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl and heteroaryl are optionally substituted independently, for each occurrence, with one, two, three or more substituents selected from the group consisting of halogen, hydroxyl and cyano; 
 Q 3  is selected from the group consisting of a bond, —C 1-4 alkyl-, —C 2 -6alkenyl-, —C 1-6 cycloalkyl-, a 5-6 membered heterocyclic ring, and phenyl; 
 Q 2 , independently for each occurrence, is selected from the group consisting of H, C 1-4 alkyl, C 2-6 alkenyl, C 1-6 cycloalkyl, a 5-6 membered heterocyclic ring, phenyl, substituted or unsubstituted aliphatic, substituted or unsubstituted heteroaliphatic, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl; 
 A 3 , independently for each occurrence, is selected from the group consisting of —NH 2 , —SH, and —OH; 
 A 4 , independently for each occurrence, is selected from the group consisting of —NH 2 , —NH—NH 2 ; —NHOH, —NH—OR″, —SH, and —OH; 
 R″ is selected from the group consisting of H and C 1-4 alkyl; 
 W 1 , independently for each occurrence, is (a) absent; or (b) selected from the group consisting of —C 1-4 alkyl-, —O—C 1-4 alkyl-, —C 1-4 alkyl-C(O)—, —C(O)—C 1-4 alkyl-, —N(R a )—C 1-4 alkyl-, —C 1-4 alkyl-O—C(O)—, —C(O)—O—C 1-4 alkyl-, —NR a —C(O)—, —C 2-6 alkenyl-, —C 2-6 alkynyl-, —C 3-6 cycloalkyl-, -phenyl-, -heteroaryl-, and heterocyclic; wherein C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, R′, phenyl, heterocyclic, and heteroaryl are optionally substituted independently, for each occurrence, with one, two, three or more substituents selected from the group consisting of C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 alkoxy, —C(O)C 1-6 alkyl, —C(O)—O—C 1-4 alkyl, cycloalkyl, heterocyclic, phenyl, heteroaryl, halogen, hydroxyl, nitro sulfoxide, sulfone, sulfonamide and cyano, wherein the cycloalkyl, heterocyclic, phenyl, or heteroaryl moiety is optionally substituted with one, two, three or more substituents selected from halogen, amino, cyano, hydroxyl, C 1-6 alkyl, phenyl, heteroaryl, and amino; 
 R′ is independently selected, for each occurrence, from the group consisting of hydrogen, substituted or unsubstituted aliphatic, and substituted or unsubstituted heteroaliphatic; Q 1  is independently selected, for each occurrence, from the group consisting of —NHR′, —N(R′) 2 , —NR a R b , —O—Si(R′) 3 , —O—SiR a R b R′, —SH, —OH, —O—C 1-6 alkyl, —S—C 1-6 alkyl, —O-aryl, —S-aryl, heteroaryl, —O-heteroaryl, —S-heteroaryl, halogen and —O—C 1-6 alkyl-NR a R b ; 
 R a  and R b  are independently selected, for each occurrence, from the group consisting of hydrogen and C 1-4 alkyl; wherein C 1-4 alkyl may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo and hydroxyl; or 
 R a  and R b , together with the nitrogen to which they are attached, may form a 4-7 membered heterocyclic ring, which may have an additional heteroatom selected from O, S, or N; wherein the 4-7 membered heterocyclic ring may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo and hydroxyl; 
 R 1  and R 2  are selected independently, for each occurrence, from the group consisting of —OH, C 1-6 alkyl, —O—C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, —C 1-6 alkyl-NR a R b , phenyl and heteroaryl; wherein C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, R a , R b , phenyl and heteroaryl, independently selected, for each occurrence, may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, hydroxyl, amino, C 1-6 alkyl, heteroaryl, and phenyl; or R 1  and R 2 , together with the silicon to which they are attached, may form a 5-8 membered heterocyclic ring, which may have one or more additional heteroatoms selected from O, S, or N; wherein the 5-8 membered heterocyclic ring may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo, amino and hydroxyl; 
 BB, independently for each occurrence, is a 5- or 6-membered cycloalkyl, heterocyclic, aryl, or heteroaryl moiety, wherein the cycloalkyl, heterocyclic, aryl, or heteroaryl moiety is optionally substituted with one, two, three or more groups represented by R BB ; wherein R 1 , independently for each occurrence, may be optionally bonded to BB; 
 each R BB  is independently selected, for each occurrence, from the group consisting of hydrogen, halogen, nitro, cyano, hydroxyl, amino, thio, —COOH, —CONHR′, substituted or unsubstituted aliphatic, substituted or unsubstituted heteroaliphatic, —C 1-4 alkyl, —O—C 1-4 alkyl, —N(Ra)—C 1-4 alkyl, —C(O)C 1-4 alkyl, —C(O)—O—C 1-4 alkyl, —C(O)—NR a R b , —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-6 cycloalkyl, heterocyclic, phenyl, phenoxy, heteroaryl, —C 1-4 alkylene-phenyl, —C 1-4 alkylene-heteroaryl, —C 1-4 alkylene-heterocyclyl, —C 2-6 alkenylene-phenyl, —C 2-6 alkenylene-heteroaryl, —C 2-6 alkenylene-heterocyclyl, —C 2-6 alkynyl-phenyl, —C 2-6 alkynyl-heteroaryl, —C 2-6 alkynyl-heterocyclyl; wherein C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, phenoxy, heterocyclyl, and heteroaryl are optionally substituted by one, two, three or more substituents selected from the group consisting of C 1-4 alkyl, C 1-4 alkoxy, —C(O)C 1-4 alkyl, —C(O)—O—C 1-4 alkyl, —C(O)—NR a R b , halogen, cyano, hydroxyl, cycloalkyl, heterocyclic, phenyl, or heteroaryl; or two R BB  together with the atoms to which they are attached form a fused 5- or 6-membered cycloalkyl or heterocyclic bicyclic ring system; 
 
         X 2  is a second ligand moiety capable of binding to and modulating a second target biomolecule; 
         Y 2  is absent or is a connector moiety covalently bound to X 2  and Z 2 ; 
         Z 2  is selected from the group consisting of: 
       
       
         
           
           
               
               
           
         
         wherein 
         W 1 , independently for each occurrence, is (a) absent; or (b) selected from the group consisting of —C 1-4 alkyl-, —O—C 1-4 alkyl-, —C 1-4 alkyl-C(O)—, —C(O)—C 1-4 alkyl-, —N(R a )—C 1-4 alkyl-, —C 1-4 alkyl-O—C(O)—, —C(O)—O—C 1-4 alkyl-, —NR a —C(O)—, —C 2-6 alkenyl-, —C 2-6 alkynyl-, —C 3-6 cycloalkyl-, -phenyl-, -heteroaryl-, and heterocyclic; wherein C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, R′, phenyl, heterocyclic, and heteroaryl are optionally substituted independently, for each occurrence, with one, two, three or more substituents selected from the group consisting of C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 alkoxy, —C(O)C 1-6 alkyl, —C(O)—O—C 1-4 alkyl, cycloalkyl, heterocyclic, phenyl, heteroaryl, halogen, hydroxyl, nitro sulfoxide, sulfone, sulfonamide and cyano, wherein the cycloalkyl, heterocyclic, phenyl, or heteroaryl moiety is optionally substituted with one, two, three or more substituents selected from halogen, amino, cyano, hydroxyl, C 1-6 alkyl, phenyl, heteroaryl, and amino; 
         R′ is independently selected, for each occurrence, from the group consisting of hydrogen, substituted or unsubstituted aliphatic, and substituted or unsubstituted heteroaliphatic; 
         Q 1  is independently selected, for each occurrence, from the group consisting of —NHR′, —N(R′) 2 , —NR a R b , —O—Si(R′) 3 , —O—SiR a R b R′, —SH, —OH, —O—C 1-6 alkyl, —S—C 1-6 alkyl, —O-aryl, —S-aryl, heteroaryl, —O-heteroaryl, —S-heteroaryl, halogen and —O—C 1-6 alkyl-NR a R b ; 
         R a  and R b  are independently selected, for each occurrence, from the group consisting of hydrogen and C 1-4 alkyl; wherein C 1-4 alkyl may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo and hydroxyl; or 
         R a  and R b , together with the nitrogen to which they are attached, may form a 4-7 membered heterocyclic ring, which may have an additional heteroatom selected from O, S, or N; wherein the 4-7 membered heterocyclic ring may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo and hydroxyl; 
         R 1  and R 2  are selected independently, for each occurrence, from the group consisting of —OH, C 2-6 alkenyl, C 3-6 cycloalkyl, phenyl and heteroaryl; wherein C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, R a , R b , phenyl and heteroaryl, independently selected, for each occurrence, may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, hydroxyl, amino, C 1-6 alkyl, heteroaryl, and phenyl; or R 1  and R 2 , together with the silicon to which they are attached, may form a 5-8 membered heterocyclic ring, which may have one or more additional heteroatoms selected from O, S, or N; wherein the 5-8 membered heterocyclic ring may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo, amino and hydroxyl; 
         R 8 , independently for each occurrence, is selected from the group consisting of H, halogen, oxo and C 1-4 alkyl; wherein C 1-4 alkyl is optionally substituted by one or more substituents selected from the group consisting of hydroxyl, amino, halo, thio. C 2-4 alkenyl, C 1-4 alkoxy, —S—C 1-4 alkyl, —CN, —COOH and —C(O)—NHR″; 
         AA, independently for each occurrence, is a 5-7 membered heterocyclic ring having one, two, or three heteroatoms, or phenyl; wherein AA is optionally substituted by one, two, or three substituents selected from the group consisting of halo and C 1-4 alkyl; wherein C 1-4 alkyl is optionally substituted by one or more substituents selected from the group consisting of hydroxyl, amino, halo, thio, C 2-4 alkenyl, C 1-4 alkoxy, —S—C 1-4 alkyl, —CN, —COOH and —C(O)—NHR″, or two substituents together with the atoms to which they are attached form a fused 5- or 6-membered cycloalkyl or heterocyclic bicyclic ring system; and 
         R″ is selected independently, for each occurrence, from the group consisting of H and C 1-4 alkyl. 
       
     
     
         4 . The therapeutic multimer compound of  claim 1 , wherein X 1  and X 2  are the same. 
     
     
         5 . The therapeutic multimer compound of  claim 1 , wherein X 1  and X 2  are different. 
     
     
         6 . A first silyl monomer capable of forming a biologically useful multimer when in contact with one, two, three or more second silyl monomers in an aqueous media, wherein the first and second silyl monomer is represented by the formula:
   X 3 —Y 3 —Z 3   (Formula III)
   and pharmaceutically acceptable salts, stereoisomers, metabolites and hydrates thereof, wherein   X 3  is a first ligand moiety capable of binding to and modulating a first target biomolecule;   Y 3  is absent or is a connector moiety covalently bound to X 3  and Z 3 ;   Z 3  is independently selected from the group consisting of:   
       
         
           
           
               
               
           
         
         
           wherein
 R W  is selected from the group consisting of a bond, —C 1-4 alkyl-, —O—C 1 -4alkyl-, —N(R a )—C 1-4 alkyl-, —C 1-4 alkyl-C(O)—, —C(O)C 1-4 alkyl-, —C 1-4 alkyl-O—C(O)—, —C(O)—O—C 1-4 alkyl-, —NR a —C(O)—, —C 2-6 alkenyl-, —C 2-6 alkynyl-, —C 3-6 cycloalkyl-, -phenyl-, -heteroaryl-, and -heterocyclic-; wherein C 1-4 alkyl, R a , R b , C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl and heteroaryl may be optionally substituted by one, two, three or more substituents selected from the group consisting of C 1 -4alkyl, C 1-4 alkoxy, —C(O)C 1-4 alkyl, —C(O)—O—C 1-4 alkyl, —C(O)—NR a R b , halogen, cyano, hydroxyl, cycloalkyl, heterocyclic, phenyl, heteroaryl, R a  and R b , wherein the cycloalkyl, heterocyclic, phenyl, or heteroaryl moiety is optionally substituted with one, two, three or more substituents selected from halogen, amino, cyano, hydroxyl, C 1-6 alkyl, phenyl, heteroaryl, and amino; 
 W 1 , independently for each occurrence, is (a) absent; or (b) selected from the group consisting of —C 1-4 alkyl-, —O—C 1-4 alkyl-, —C 1-4 alkyl-C(O)—, —C(O)—C 1-4 alkyl-, —N(R a )—C 1-4 alkyl-, —C 1-4 alkyl-O—C(O)—, —C(O)—O—C 1-4 alkyl-, —NR a —C(O)—, —C 2-6 alkenyl-, —C 2-6 alkynyl-, —C 3-6 cycloalkyl-, -phenyl-, -heteroaryl-, and heterocyclic; wherein C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, R′, phenyl, heterocyclic, and heteroaryl are optionally substituted independently, for each occurrence, with one, two, three or more substituents selected from the group consisting of C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-4 alkoxy, —C(O)C 1-6 alkyl, —C(O)—O—C 1-4 alkyl, cycloalkyl, heterocyclic, phenyl, heteroaryl, halogen, hydroxyl, nitro sulfoxide, sulfone, sulfonamide and cyano, wherein the cycloalkyl, heterocyclic, phenyl, or heteroaryl moiety is optionally substituted with one, two, three or more substituents selected from halogen, amino, cyano, hydroxyl, C 1-6 alkyl, phenyl, heteroaryl, and amino; 
 R′ is independently selected, for each occurrence, from the group consisting of hydrogen, substituted or unsubstituted aliphatic, and substituted or unsubstituted heteroaliphatic; 
 Q 1  is independently selected, for each occurrence, from the group consisting of —NHR′, —N(R′) 2 , —NR a R b , —O—Si(R′) 3 , —O—SiR a R b R′, —SH, —OH, —O—C 1-6 alkyl, —S—C 1-6 alkyl, —O-aryl, —S-aryl, heteroaryl, —O-heteroaryl, —S-heteroaryl, halogen and —O—C 1-6 alkyl-NR a R b ; 
 R a  and R b  are independently selected, for each occurrence, from the group consisting of hydrogen, C 1-4 alkyl, —O—C 1-4 alkyl and —NH—C 1-4 alkyl; wherein C 1-4 alkyl may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo and hydroxyl; or 
 R a  and R b , together with the nitrogen to which they are attached, may form a 4-7 membered heterocyclic ring, which may have one or more additional heteroatoms selected from O, S, or N; wherein the 4-7 membered heterocyclic ring may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo, amino and hydroxyl; 
 R 1  and R 2  are selected independently, for each occurrence, from the group consisting of —OH, C 1-6 alkyl, —O—C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, —C 1-6 alkyl-NR a R b , phenyl and heteroaryl; wherein C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, R a , R b , phenyl and heteroaryl, independently selected, for each occurrence, may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, hydroxyl, amino, C 1-6 alkyl, heteroaryl, and phenyl; or R 1  and R 2 , together with the silicon to which they are attached, may form a 5-8 membered heterocyclic ring, which may have one or more additional heteroatoms selected from O, S, or N; wherein the 5-8 membered heterocyclic ring may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo, amino and hydroxyl; 
 BB, independently for each occurrence, is a 4-7-membered cycloalkyl, heterocyclic, aryl, or heteroaryl moiety, wherein the cycloalkyl, heterocyclic, aryl, or heteroaryl moiety is optionally substituted with one, two, three or more groups represented by R BB ; wherein R 1 , independently for each occurrence, may be optionally bonded to BB; 
 each R BB  is independently selected, for each occurrence, from the group consisting of hydrogen, halogen, nitro, cyano, hydroxyl, amino, thio, —COOH, —CONHR′, substituted or unsubstituted aliphatic, substituted or unsubstituted heteroaliphatic, —C 1-4 alkyl, —O—C 1-4 alkyl, —N(R a )—C 1-4 alkyl, —C(O)C 1-4 alkyl, —C(O)—O—C 1-4 alkyl, —C(O)—NR a R b , —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-6 cycloalkyl, heterocyclic, phenyl, phenoxy, heteroaryl, —C 1-4 alkylene-phenyl, —C 1-4 alkylene-heteroaryl, —C 1-4 alkylene-heterocyclyl, —C 2-6 alkenylene-phenyl, —C 2-6 alkenylene-heteroaryl, —C 2-6 alkenylene-heterocyclyl, —C 2-6 alkynyl-phenyl, —C 2-6 alkynyl-heteroaryl, —C 2-6 alkynyl-heterocyclyl; wherein C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, phenoxy, heterocyclyl, and heteroaryl are optionally substituted by one, two, three or more substituents selected from the group consisting of C 1-4 alkyl, C 1-4 alkoxy, —C(O)C 1-4 alkyl, —C(O)—O—C 1-4 alkyl, —C(O)—NR a R b , halogen, cyano, hydroxyl, cycloalkyl, heterocyclic, phenyl, or heteroaryl; or two R BB  together with the atoms to which they are attached form a fused 5- or 6-membered cycloalkyl or heterocyclic bicyclic ring system; 
 R W  is selected from the group consisting of a bond, —C 1-4 alkyl-, —O—C 1 -4alkyl-, —N(R a )—C 1-4 alkyl-, —C 1-4 alkyl-C(O)—, —C(O)C 1-4 alkyl-, —C 1-4 alkyl-O—C(O)—, —C(O)—O—C 1-4 alkyl-, —NR a —C(O)—, —C 2-6 alkenyl-, —C 2-6 alkynyl-, —C 3-6 cycloalkyl-, -phenyl-, -heteroaryl-, and -heterocyclic-; wherein C 1-4 alkyl, R a , R b , C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl and heteroaryl may be optionally substituted by one, two, three or more substituents selected from the group consisting of C 1-4 alkyl, C 1-4 alkoxy, —C(O)C 1-4 alkyl, —C(O)—O—C 1-4 alkyl, —C(O)—NR a R b , halogen, cyano, hydroxyl, cycloalkyl, heterocyclic, phenyl, heteroaryl, R a  and R b , wherein the cycloalkyl, heterocyclic, phenyl, or heteroaryl moiety is optionally substituted with one, two, three or more substituents selected from halogen, amino, cyano, hydroxyl, C 1-6 alkyl, phenyl, heteroaryl, and amino; and 
 
         
       
       
         
           
           
               
               
           
         
         
           wherein
 Q 2A  may be selected from the group consisting of a bond, —O—C 1-6 alkyl-, —N(R′)—C 1-6 alkyl-, and —S—C 1-6 alkyl-; 
 W 1 , independently for each occurrence, is (a) absent; or (b) selected from the group consisting of —C 1-4 alkyl-, —O—C 1-4 alkyl-, —N(R a )—C 1-4 alkyl-, —C 1-4 alkyl-C(O)—, —C(O)C 1-4 alkyl-, —C 1-4 alkyl-O—C(O)—, —C(O)—O—C 1-4 alkyl-, —NR′—C(O)—, —C 2 -6alkenyl-, —C 2-6 alkynyl-, —C 3-6 cycloalkyl-, -phenyl-, and -heteroaryl-; wherein C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, R′, R a  phenyl and heteroaryl may be optionally substituted independently, for each occurrence, with one, two, three or more substituents selected from the group consisting of C 1-4 alkyl, C 1-4 alkoxy, —C(O)C 1-6 alkyl, —C(O)—O—C 1-4 alkyl, halogen, hydroxyl, nitro, carbamate, carbonate and cyano; 
 W 1A , independently for each occurrence, is (a) absent; or (b) selected from the group consisting of —C 1-4 alkyl-, —C 1-4 alkyl-O—, —C 1-4 alkyl-N(R a )—, —C 1-4 alkyl-C(O)—, —C(O)C 1-4 alkyl-, —C 1-4 alkyl-O—C(O)—, —C(O)—O—C 1-4 alkyl-, —C(O)—NR′—, —C 2 -6alkenyl-, —C 2-6 alkynyl-, —C 3-6 cycloalkyl-, -phenyl-, and -heteroaryl-; wherein C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, R′, R a  phenyl and heteroaryl may be optionally substituted independently, for each occurrence, with one, two, three or more substituents selected from the group consisting of C 1-4 alkyl, C 1-4 alkoxy, —C(O)C 1-6 alkyl, —C(O)—O—C 1-4 alkyl, halogen, hydroxyl, nitro, carbamate, carbonate and cyano; 
 R′ is independently selected, for each occurrence, from the group consisting of hydrogen, substituted or unsubstituted aliphatic, and substituted or unsubstituted heteroaliphatic; 
 Q 1  and Q 1A  are independently selected, for each occurrence, from the group consisting of —NH(R′) 2 , —N(R′) 2 , —NR a R b , —O—Si(R′) 3 , —O—SiR a R b R′, —SH, —OH, —O—C 1-6 alkyl, —S—C 1-6 alkyl, —O-aryl, —S-aryl, heteroaryl, —O-heteroaryl, —S-heteroaryl, halogen and —O—C 1-6 alkyl-NR a R b ; 
 R a  and R b  are independently selected, for each occurrence, from the group consisting of hydrogen and C 1-4 alkyl; wherein C 1-4 alkyl may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo and hydroxyl; or 
 R a  and R b , together with the nitrogen to which they are attached, may form a 4-7 membered heterocyclic ring, which may have an additional heteroatom selected from O, S, or N; wherein the 4-7 membered heterocyclic ring may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo and hydroxyl; 
 R 1  and R 2  are selected independently, for each occurrence, from the group consisting of —OH, C 1-6 alkyl, —O—C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, —C 1-6 alkyl-NR a R b , phenyl and heteroaryl; wherein C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, R a , R b , phenyl and heteroaryl, independently selected, for each occurrence, may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, hydroxyl, amino, C 1-6 alkyl, heteroaryl, and phenyl; or R 1  and R 2 , together with the silicon to which they are attached, may form a 5-8 membered heterocyclic ring, which may have one or more additional heteroatoms selected from O, S, or N; wherein the 5-8 membered heterocyclic ring may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo, amino and hydroxyl; 
 W 2A  is CR W2A , 
 R W2A  is selected from the group consisting of hydrogen, C 1-4 alkyl, —O—C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl and heteroaryl; wherein C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl and heteroaryl are optionally substituted independently, for each occurrence, with one, two, three or more substituents selected from the group consisting of halogen, hydroxyl and cyano; 
 BB, independently for each occurrence, is a 4-7-membered cycloalkyl, heterocyclic, aryl, or heteroaryl moiety; wherein the cycloalkyl, heterocyclic, aryl, or heteroaryl moiety is optionally substituted with one, two, three or more groups represented by R BB ; wherein R 1 , independently for each occurrence, may be optionally bonded to BB; 
 each R BB  is independently selected, for each occurrence, from the group consisting of hydrogen, halogen, nitro, cyano, hydroxyl, amino, thio, —COOH, —CONHR′, substituted or unsubstituted aliphatic, substituted or unsubstituted heteroaliphatic, —C 1-4 alkyl, —O—C 1-4 alkyl, —N(R a )—C 1-4 alkyl, —C(O)C 1-4 alkyl, —C(O)—O—C 1-4 alkyl, —C(O)—NR a R b , —C 2-6 alkenyl, —C 2-6 alkynyl, —C 3-6 cycloalkyl, heterocyclic, phenyl, phenoxy, heteroaryl, —C 1-4 alkylene-phenyl, —C 1-4 alkylene-heteroaryl, —C 1-4 alkylene-heterocyclyl, —C 2-6 alkenylene-phenyl, —C 2-6 alkenylene-heteroaryl, —C 2-6 alkenylene-heterocyclyl, —C 2-6 alkynyl-phenyl, —C 2-6 alkynyl-heteroaryl, —C 2-6 alkynyl-heterocyclyl; wherein C 1-4 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-6 cycloalkyl, phenyl, phenoxy, heterocyclyl, and heteroaryl are optionally substituted by one, two, three or more substituents selected from the group consisting of C 1-4 alkyl, C 1-4 alkoxy, —C(O)C 1-4 alkyl, —C(O)—O—C 1-4 alkyl, —C(O)—NR a R b , halogen, cyano, hydroxyl, cycloalkyl, heterocyclic, phenyl, or heteroaryl; or two R BB  together with the atoms to which they are attached form a fused 5- or 6-membered cycloalkyl or heterocyclic bicyclic ring system. 
 
         
       
     
     
         7 . The first silyl monomer of  claim 6 , wherein Z 3  is independently selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         8 . The first silyl monomer of  claim 7 , wherein W 1  is absent. 
     
     
         9 . The first silyl monomer of  claim 7 , wherein W 1  is —C 1-4 alkyl-. 
     
     
         10 . The first silyl monomer of  claim 7 , wherein W 1  is -phenyl-. 
     
     
         11 . The first silyl monomer of  claim 7 , wherein BB is phenyl or heteroaryl. 
     
     
         12 . The first silyl monomer of  claim 7 , wherein R 1  and R 2  are methyl. 
     
     
         13 . The first silyl monomer of  claim 7 , wherein Q 1  is —OH. 
     
     
         14 . The first silyl monomer of  claim 7 , wherein Q 1  and R 2  are —OH. 
     
     
         15 . The first silyl monomer of  claim 6 , wherein Z 3  is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         wherein 
         R BB  is independently selected, for each occurrence, from the group consisting of hydrogen, halogen, nitro, cyano, hydroxyl, amino, thio, —COOH, —CONHR′, substituted or unsubstituted aliphatic, and substituted or unsubstituted heteroaliphatic; 
         W 1 , independently selected for each occurrence, is (a) absent or (b) —C 1-4 alkyl-; 
         Q 1  is independently selected for each occurrence from the group consisiting of —NHR′, —N(R′) 2 , —NR a R b , —O—Si(R′) 3 , —O—SiR a R b R′, —SH, —OH, —O—C 1-6 alkyl, —S—C 1-6 alkyl, —O-aryl, —S-aryl, heteroaryl, —O-heteroaryl, —S-heteroaryl, halogen and —O—C 1-6 alkyl-NR a R b ; 
         R 1  and R 2 , independently selected, for each occurrence, are C 1-6 alkyl. 
       
     
     
         16 . The first silyl monomer of  claim 6 , wherein Z 3  is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         wherein 
         R 1  and R 2  are selected independently, for each occurrence, from the group consisting of —OH, C 1-6 alkyl, —O—C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, —C 1-6 alkyl-NR a R b , phenyl and heteroaryl; wherein C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, R a , R b , phenyl and heteroaryl, independently selected, for each occurrence, may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, hydroxyl, amino, C 1-6 alkyl, heteroaryl, and phenyl; or R 1  and R 2 , together with the silicon to which they are attached, may form a 5-8 membered heterocyclic ring, which may have one or more additional heteroatoms selected from O, S, or N; wherein the 5-8 membered heterocyclic ring may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo, amino and hydroxyl; 
         R a  and R b  are independently selected, for each occurrence, from the group consisting of hydrogen and C 1-4 alkyl; wherein C 1-4 alkyl may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo and hydroxyl; or 
         R a  and R b , together with the nitrogen to which they are attached, may form a 4-7 membered heterocyclic ring, which may have an additional heteroatom selected from O, S, or N; wherein the 4-7 membered heterocyclic ring may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo and hydroxyl; and 
         m is 0, 1, 2, 3 or 4. 
       
     
     
         17 . The first silyl monomer of  claim 6 , wherein Z 3  is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         wherein 
         R 1  and R 2 , independently selected, for each occurrence, from the group consisting of C 1-6 alkyl and C 1-6 alkoxy; 
         m is 0, 1, 2, 3 or 4; 
         R″ is selected from the group consisting of —C 1-2 alkyl-, —O—C 1-2 alkyl-, and —NH(C═O)C 1-2  alkyl; wherein C 1-2 alkyl is optionally substituted independently, for each occurrence, with one, two, three or more fluorines. 
       
     
     
         18 . The first silyl monomer of  claim 6 , wherein Z 3  is independently selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         19 . The first silyl monomer of  claim 18 , wherein W 1  is —C 1-4 alkyl- and W 1A  is absent. 
     
     
         20 . The first silyl monomer of  claim 18 , wherein W 1  and W 1A  are —C 1-4 alkyl-. 
     
     
         21 . The first silyl monomer of  claim 18 , wherein W 1  and W 1A  are absent. 
     
     
         22 . The first silyl monomer of  claim 18 , wherein BB is phenyl or heteroaryl. 
     
     
         23 . The first silyl monomer of  claim 18 , where BB is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         24 . The first silyl monomer of  claim 6 , wherein Z 3  is independently selected from the group consisting of: 
       
         
           
           
               
               
           
         
         wherein 
         W 1  and W 1A , independently selected, for each occurrence, are (a) absent or (b) —C 1-4 alkyl-; 
         R 1  and R 2  are selected independently, for each occurrence, from the group consisting of —OH, C 1-6 alkyl, —O—C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, —C 1-6 alkyl-NR a R b , phenyl and heteroaryl; wherein C 1-6 alkyl, C 2-6 alkenyl, C 3-6 cycloalkyl, R a , R b , phenyl and heteroaryl, independently selected, for each occurrence, may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, hydroxyl, amino, C 1-6 alkyl, heteroaryl, and phenyl; or R 1  and R 2 , together with the silicon to which they are attached, may form a 5-8 membered heterocyclic ring, which may have one or more additional heteroatoms selected from O, S, or N; wherein the 5-8 membered heterocyclic ring may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo, amino and hydroxyl; 
         R a  and R b  are independently selected, for each occurrence, from the group consisting of hydrogen and C 1-4 alkyl; wherein C 1-4 alkyl may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo and hydroxyl; or 
         R a  and R b , together with the nitrogen to which they are attached, may form a 4-7 membered heterocyclic ring, which may have an additional heteroatom selected from O, S, or N; wherein the 4-7 membered heterocyclic ring may be optionally substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo and hydroxyl; and 
         m is 0, 1, 2, 3 or 4. 
       
     
     
         25 - 87 . (canceled) 
     
     
         88 . A method of modulating two or more target biomolecule domains substantially simultaneously comprising:
 contacting an aqueous composition comprising said biomoleular target with a first monomer represented by:
   X 1 —Y 1 —Z 1   (Formula I)
 
 and pharmaceutically acceptable salts, stereoisomers, metabolites and hydrates thereof, wherein 
 X 1  is a first ligand moiety capable of binding to and modulating a first target biomolecule domain; and 
   a second monomer represented by:
   X 2 —Y 2 —Z 2   (Formula II),
 
 and pharmaceutically acceptable salts, stereoisomers, metabolites and hydrates thereof, wherein 
 X 2  is a ligand moiety capable of binding to and modulating a second target biomolecule domain; 
   wherein upon contact with the aqueous composition, said first monomer and said second monomer forms a multimer that binds to the first target biomolecule domain and the second target biomolecule domain.   
     
     
         89 - 96 . (canceled) 
     
     
         97 . A compound selected from the group consisting of: (4-(3-(aminomethyl)phenyl)piperidin-1-yl)(4-((hydroxydimethylsilyl)methoxy)phenyl)methanone; N-(4-(4-(3-(aminomethyl)phenyl)-piperidine-1-carbonyl)-2-chlorophenyl)-2-(hydroxydimethylsilyl)acetamide; N-(3-(4-(3-(aminomethyl)phenyl)piperidine-1-carbonyl)phenyl)-2-(hydroxydimethylsilyl)acetamide; (4-(3-(aminomethyl)phenyl)piperidin-1-yl)(3-chloro-4-((hydroxydimethylsilyl)methoxy)-phenyl)methanone; (4-(3-(aminomethyl)phenyl)piperidin-1-yl)(3-((hydroxydimethylsilyl)-methoxy)phenyl)methanone; (4-(3-(aminomethyl)phenyl)piperidin-1-yl)(3-chloro-5-((hydroxydimethylsilyl)methoxy)phenyl)methanone; N-(4-(4-(3-(aminomethyl)phenyl)-piperidine-1-carbonyl)phenyl)-2-(hydroxydimethylsilyl)acetamide; and pharmaceutically acceptable salts, stereoisomers, metabolites and hydrates thereof.