Bridged Macrocyclic Module Compositions

Abstract

This invention is related to the fields of organic chemistry and nanotechnology. In particular, it relates to materials and methods for the preparation of organic synthons and bridged macrocyclic module components. The bridge macrocyclic module compounds may be used to prepare macrocyclic module compositions such as nanofilms, which may be useful for filtration.

We claim: 
     
         1 . A bridged macrocyclic module compound of the formula: 
       
         
           
           
               
               
           
         
         wherein the compound further comprises a bridge moiety A having two or more termini, wherein at least two of said two or more termini are coupled to the compound; 
         wherein each Q is a synthon independently selected from the group consisting of: benzene, cyclohexadiene, cyclopentadiene, naphthalene, anthracene, phenylene, phenanthracene, pyrene, triphenylene, phenanthrene, pyridine, pyrimidine, pyridazine, biphenyl, bipyridyl, cyclohexane, cyclohexene, decalin, piperidine, pyrrolidine, morpholine, piperazine, pyrazolidine, quinuclidine, tetrahydropyran, dioxane, tetrahydrothiophene, tetrahydrofuran, pyrrole, cyclopentane, cyclopentene, triptycene, adamantane, bicyclo[2.2.1]heptane, bicyclo[2.2.1]heptene, bicyclo[2.2.2]octane, bicyclo[2.2.2]octene, bicyclo[3.3.0]octane, bicyclo[3.3.0]octene, bicyclo[3.3.1]nonane, bicyclo[3.3.1]nonene, bicyclo[3.2.2]nonane, bicyclo[3.2.2]nonene, bicyclo[4.2.2]decane, 7-azabicyclo[2.2.1]heptane, 1,3-diazabicyclo[2.2.1]heptane, spiro[4.4]nonane, —OCH 2 CH 2 —, —(CH 2 ) n C≡C(CH 2 ) n —, —(CH 2 ) n CH═CH(CH 2 ) n —, 
       
       
         
           
           
               
               
           
         
       
       —(CH 2 ) n —, —C(O)O(CH 2 ) n —, —(CH 2 ) n C(O)NR—; —S m —, —(CH 2 ) n SiMe 2 (CH 2 ) n —, —(CH 2 ) n NR(CH 2 ) n —, and —(CH 2 ) n CH(OH)—;
 wherein each synthon Q may optionally be substituted with one or more functional groups for coupling the synthon to at least a second bridged macrocyclic module or to a substrate; wherein each synthon may optionally be substituted with one or more lipophilic and/or hydrophilic groups; 
 wherein each L is a linkage moiety independently selected from the group consisting of a direct bond, —NRC(O)—, —OC(O)—, —O—, —S—S—, —S—, —NR—, —(CRR) p —, —CH 2 NH—, —CH═N—, —C(O)S—, —C(O)O—, —C≡C—, —C≡C—C≡C—, —CH(OH)—, —HC═CH—, —NHC(O)NH—, —NHC(O)O—, —NHCH 2 NH—, —NHCH 2 CH(OH)CH 2 NH—, —N═CH(CH 2 ) p CH═N—, —CH 2 CH(OH)CH 2 —, —N═CH(CH 2 ) h CH═N—, —CH═N—NH—, —OC(O)O—, —OP(O)(OH)O—, —CH(OH)CH 2 NH—, —CH(OH)CH 2 —, —CH(OH)C(CH 3 ) 2 C(O)O—, 
 
       
         
           
           
               
               
           
         
         wherein the linkage is independently configured in either of two possible configurations, forward and reverse, with respect to the synthons it couples together; 
         wherein the bridge moiety A is selected from the group consisting of 
       
       
         
           
           
               
               
           
         
       
       —O—(CH 2 ) m —O—; —{NH—CHR—(CO)} m —O—; —O—(CF 2 ) m —O—; —(S) m —; —O(CH 2 CH 2 O) m —; —(OCH(CH 3 )CH 2 ) m O—; 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein the at least two termini of the bridge moiety may be conjugated to the compound through a linkage moiety L, wherein L is as defined above; 
         wherein R is independently selected from the group consisting of hydrogen and alkyl; 
         wherein Ph is phenyl; 
         wherein X is selected from the group consisting of F, Cl, Br, and I; 
         wherein X′ is independently H or a functional group for linking to at least a second bridged macrocyclic moiety or a substrate; 
         wherein each R 2  is independently selected from a bond for linking to a synthon or a functional group selected from the group consisting of hydrogen, an activated acid, —OH, —C(O)OH, —C(O)H, —C(O)OCH 3 , —C(O)Cl, —NRR, —NRRR + , —MgX, —Li, —OLi, —OK, —ONa, —SH, —C(O)(CH 2 ) 2 C(O)OCH 3 , —NH-alkyl-C(O)CH 2 CH(NH 2 )CO 2 -alkyl, —CH═CH 2 , —CH═CHR, —CH═CRR, 4-vinylaryl, —C(O)CH═CH 2 , —NHC(O)CH═CH 2 , —C(O)CH═CH(C 6 H 5 ), 
       
       
         
           
           
               
               
           
         
       
       —OH, —OC(O)(CH 2 ) 2 C(O)OCH 3 , —OC(O)CH═CH 2 , 
       
         
           
           
               
               
           
         
       
       —P(O)(OH)(OX), or —P(═O)(O − )O(CH 2 ) s NR 3   + ;
 wherein n′ is from 4 to 50; 
 wherein n is 1-22; 
 wherein m is 2-14; 
 wherein p is 1-6; 
 wherein h is 1-4; 
 wherein r is 1-50; and 
 wherein s is 1-4. 
 
     
     
         2 . The compound of  claim 1 , wherein the two or more termini of said bridge moiety are coupled to synthons. 
     
     
         3 . The compound of  claim 1 , wherein the two or more termini of said bridge moiety are coupled to L moieties, with the proviso that said L moieties to which the termini are coupled are not direct bonds. 
     
     
         4 . The compound of  claim 1 , wherein n′ is from 4 to 24. 
     
     
         5 . The compound of  claim 1 , wherein n′ is from 6 to 12. 
     
     
         6 . The compound of  claim 1 , having the formula: 
       
         
           
           
               
               
           
         
       
       wherein each Q 1 , Q 2 , Q 3 , and L are independently selected. 
     
     
         7 . The compound of  claim 1 , having the formula: 
       
         
           
           
               
               
           
         
       
       wherein each Q 1 , Q 2 , Q 3 , and L are independently selected. 
     
     
         8 . The compound of  claim 1 , having the formula: 
       
         
           
           
               
               
           
         
       
       wherein each Q 1 , Q 2 , Q 3 , and L are independently selected. 
     
     
         9 . The compound of  claims 6 - 8 , wherein each Q 1  is the same synthon. 
     
     
         10 . The compound of  claims 6 - 8 , wherein each Q 2  is the same synthon. 
     
     
         11 . The compound of  claims 6 - 8 , wherein each Q 3  is the same synthon. 
     
     
         12 . The compound of  claims 6 - 8 , wherein each Q 1 , Q 2 , and Q 3  is independently selected from the group consisting of 
       
         
           
           
               
               
           
         
         wherein each X′ is independently H or a functional group for coupling the synthon to at least a second bridged macrocyclic module or to a substrate; 
         wherein each J is an independently selected functional group for coupling the synthon to an adjacent synthon within said bridged macrocyclic module, and wherein each X 1  is an independently selected functional group for coupling the synthon to the bridge moiety. 
       
     
     
         13 . The compound of  claim 12 , wherein each Q 1 , Q 2 , and Q 3  is independently selected from the group consisting of 
       
         
           
           
               
               
           
         
       
     
     
         14 . The compound of  claim 12 , wherein each Q 1 , Q 2 , and Q 3  is independently selected from the group consisting of 
       
         
           
           
               
               
           
         
       
     
     
         15 . The compound of  claims 6 - 8 , wherein each L between the synthons are the same. 
     
     
         16 . The compound of  claims 6 - 8 , wherein each L between the bridge moiety and the synthons are the same. 
     
     
         17 . The compound of  claim 1 , wherein the synthons are cyclic synthons. 
     
     
         18 . The compound of  claim 1 , wherein the synthons are acyclic synthons. 
     
     
         19 . The compound of  claim 1 , wherein each L is a direct bond. 
     
     
         20 . The compound of  claim 1 , wherein each L is a linkage independently selected from the group consisting of —NRC(O)—, —OC(O)—, —O—, —S—S—, —S—, —NR—, —(CRR) p —, —CH 2 NH—, —C(O)S—, —C(O)O—, —C≡C—, —C≡C—C≡C—, —CH(OH)—, —HC═CH—, —NHC(O)NH—, —NHC(O)O—, —NHCH 2 NH—, —NHCH 2 CH(OH)CH 2 NH—, —N═CH(CH 2 ) p CH═N—, —CH 2 CH(OH)CH 2 —, —NH(CH 2 ) h CH═N—, —CH═N—NH—, —OC(O)O—, —OP(O)(OH)O—, —CH(OH)CH 2 NH—, —CH(OH)CH 2 —, —CH(OH)C(CH 3 ) 2 C(O)O—, 
       
         
           
           
               
               
           
         
       
     
     
         21 . The compound of  claim 1 , wherein the bridge moiety further comprises a surface attachment group. 
     
     
         22 . The compound of  claim 1 , wherein the bridge moiety further comprises a lipophilic group. 
     
     
         23 . The compound of  claim 1 , wherein the bridge moiety comprises a functional group for coupling the compound to at least a second bridged macrocyclic module compound. 
     
     
         24 . The compound of  claim 1 , wherein the bridge moiety comprises a polymerization center. 
     
     
         25 . The compound of  claim 1 , wherein the bridged macrocyclic module compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein R o  is H, alkyl, or a lipophilic group; wherein R′ is a natural α-amino acid side chain; wherein R 1  is CH 2 CO 2 (CH 2 ) 15 CH 3 ; and wherein the structure 
       
       
         
           
           
               
               
           
         
       
       is benzene or cyclohexane. 
     
     
         26 . A nanofilm comprising a plurality of bridged macrocyclic modules of  claim 1 . 
     
     
         27 . The nanofilm of  claim 26 , wherein the thickness of the nanofilm composition is less than about 30 nanometers. 
     
     
         28 . The nanofilm of  claim 26 , wherein the thickness of the nanofilm composition is less than about 6 nanometers. 
     
     
         29 . The nanofilm of  claim 26 , wherein the nanofilm is impermeable to viruses and larger species. 
     
     
         30 . The nanofilm of  claim 26 , wherein the nanofilm is impermeable to immunoglobulin G and larger species. 
     
     
         31 . The nanofilm of  claim 26 , wherein the nanofilm is impermeable to albumin and larger species. 
     
     
         32 . The nanofilm of  claim 26 , wherein the nanofilm is impermeable to β2-Microglobulin and larger species. 
     
     
         33 . The nanofilm of  claim 26 , wherein the nanofilm is permeable only to water and smaller species. 
     
     
         34 . The nanofilm of  claim 26 , wherein the nanofilm has a molecular weight cut-off of 13 kDa. 
     
     
         35 . The nanofilm of  claim 26 , wherein the nanofilm has a molecular weight cut-off of 190 Da. 
     
     
         36 . The nanofilm of  claim 26 , wherein the nanofilm has a molecular weight cut-off of 100 Da. 
     
     
         37 . The nanofilm of  claim 26 , wherein the nanofilm has a molecular weight cut-off of 45 Da. 
     
     
         38 . The nanofilm of  claim 26 , wherein the nanofilm has a molecular weight cut-off of 20 Da. 
     
     
         39 . The nanofilm of  claim 26 , wherein the nanofilm has high permeability for water molecules and Na+, K+, and Cs+ in water. 
     
     
         40 . The nanofilm of  claim 26 , wherein the nanofilm has low permeability for glucose and urea. 
     
     
         41 . The nanofilm of  claim 26 , wherein the nanofilm has high permeability for water molecules and Cl− in water. 
     
     
         42 . The nanofilm of  claim 26 , wherein the nanofilm has high permeability for water molecules and K+ in water, and low permeability for Na+ in water. 
     
     
         43 . The nanofilm of  claim 26 , wherein the nanofilm has high permeability for water molecules and Na+ in water, and low permeability for K+ in water. 
     
     
         44 . The nanofilm of  claim 26 , wherein the nanofilm has low permeability for urea, creatinine, Li+, Ca2+, and Mg2+ in water. 
     
     
         45 . The nanofilm of  claim 26 , wherein the nanofilm has high permeability for Na+, K+, hydrogen phosphate, and dihydrogen phosphate in water. 
     
     
         46 . The nanofilm of  claim 26 , wherein the nanofilm has high permeability for Na+, K+, and glucose in water. 
     
     
         47 . The nanofilm of  claim 26 , wherein the nanofilm has low permeability for myoglobin, ovalbumin, and albumin in water. 
     
     
         48 . The nanofilm of  claim 26 , wherein the nanofilm has high permeability for organic compounds and low permeability for water. 
     
     
         49 . The nanofilm of  claim 26 , wherein the nanofilm has low permeability for organic compounds and high permeability for water. 
     
     
         50 . The nanofilm of  claim 26 , wherein the nanofilm has low permeability for water molecules and high permeability for helium and hydrogen gases. 
     
     
         51 . A nanofilm composition comprising at least two layers of the nanofilm of  claim 26 . 
     
     
         52 . The nanofilm of  claim 51 , wherein the nanofilm composition comprises at least one spacing layer between any two of the nanofilm layers. 
     
     
         53 . The nanofilm of  claim 52 , wherein the spacing layer comprises a layer of a polymer, a gel, or inorganic particles. 
     
     
         54 . The nanofilm of  claim 26 , wherein the nanofilm is deposited on a substrate. 
     
     
         55 . The nanofilm of  claim 54 , wherein the substrate is porous. 
     
     
         56 . The nanofilm of  claim 54 , wherein the nanofilm is coupled to the substrate through biotin-strepavidin mediated interaction. 
     
     
         57 . A method of filtration, comprising using a nanofilm of  claim 26  to separate components from fluid. 
     
     
         58 . A method of making a bridged macrocyclic module compound of  claim 1 , comprising:
 (a) providing a bridged program director compound of the structure   
       
         
           
           
               
               
           
         
         wherein Q 1  is a synthon; 
         wherein A is a bridge moiety; 
         wherein A is conjugated to Q 1  through a linkage moiety L; 
         wherein each J 1  is a functional group for coupling an adjacent synthon; and 
         wherein n′ is 4-25; and 
         (b) reacting a synthon or a synthon multimer with said bridged program director compound to form a bridged macrocyclic module compound. 
       
     
     
         59 . A method of making a bridged macrocyclic module compound of  claim 1 , comprising:
 (a) providing a macrocyclic moiety compound, wherein the macrocyclic moiety compound contains from 4 to 50 synthons; and   (b) reacting a bridge moiety comprising at least two termini with said macrocyclic moiety compound to form a bridged macrocyclic module compound.