foldamers are created to imitate natural species such as proteins and dna.1 , 2 , 3 , 4 , 5 , 6 it is the most important goal for foldamer chemists to thoroughly understand complex assembly behaviours of natural species and to perform similar biological functions . as natural counterparts , many artificial peptides could form stable helical conformations and further selfassemble into diverse aggregates . foldamers , such as oligo(mphenyleneethynylene)s [ oligo(mpe)s ] and aromatic tertiary amides , for example , seemed to be too  cosy  to further aggregate towards tertiary or quaternary folds , whereas the second structure of them all , no matter if it was a helix or a coil , could be well adjusted in solution.4 , 5 , 6 , 8 in particular , foldamerbased liquid crystals ( lcs ) are seldom reported , although they are popular for peptidomimetics.7 , 9 
  notably , moore and coworkers have found that oligo(mpeme)s could form a hexagonal structure with helical backbones in the solid state ( scheme  1).10 yashima and coworkers have reported that poly(mpe)s with amide side chains also form a similar structure.11 a hexagonal pebased lc phase has not yet been reported , although hexagonal lcs are common . onsager 's theory predicts that assemblies of molecules with a high aspect ratio will spontaneously form a lc phase above a critical concentration through an entropydriven process.12 however , it seemed difficult for a large number of mpebased foldamers reported previously to assemble into such fibres.4 we plan to rebuild the classic pe scaffold , so as to realise a higherorder fold in the fluid . our new strategy is that linear ppes are simply linked by chiral carbon atoms ( scheme  1 ) . the introduction of chiral elements could favour the formation of helical scaffolds and further assembly.13 , 14 in this paper , a series of chiral methylenepphenyleneethynylene ( mppe ) oligomers with 4isopropoxycarbonyl phenylamino side groups were successfully prepared ( scheme  2 ) . the hexamers and octamers can form the hexagonal lytropic lc phases in ch2cl2 as the concentrations reach the critical values . here , we present the results and corresponding analyses . reaction conditions : a )  cubf4(ch3cn)4 , tri(otolyl)phosphine , nboclproline , ms 3   , 35  c , 7  d , ch2cl2 , 70  % for 5 , 73  % for 6 ; b )  csf , acoh , 60  c , 5  h , thf , 95  % ; c )  bf3et2o , 60  c , 5  h , thf / h2o,>98  % ; d )  7 , 4 , cubf4(ch3cn)4 , tri(otolyl)phosphine , nboclproline , ms 3   , 35  c , 7  d , ch2cl2 , 61  % for 10 , 65  % for 11 ; e )  csf , acoh , 60  c , 6  h , thf , 91  % ; f )  bf3et2o , 60  c , 6  h , thf / h2o,>95  % ; g )  3 , 4 , cubf4(ch3cn)4 , tri(otolyl)phosphine , nboclproline , ms 3   , 20  c , 1  d , ch2cl2 , 26  % ; h )  7 , 4 , cubf4(ch3cn)4 , tri(otolyl)phosphine , nboclproline , ms 3   , 30  c , 3  d , ch2cl2 , 31  % ; i )  12 , 4 , cubf4(ch3cn)4 , tri(otolyl)phosphine , nboclproline , ms 3   , 30  c , 5  d , ch2cl2 , 30  % for 17 , 35  % for 18 ; j )  csf , acoh , 60  c , 5  h , thf , 85  % ; k )  12 , noctyl 4aminobenzoate , cubf4(ch3cn)4 , tri(otolyl)phosphine , nboclproline , ms 3   , 30  c , 3  d , ch2cl2 , 26  % . notably , moore and coworkers have designed many foldamers with a twistsense bias by introducing a single chiral unit to the mpe backbone.13a , 13e in contrast , the mppe scaffold is closer to a peptide structure with rigid amide units linked by chiral carbon atoms . to construct the chiral carbon in mppe oligomers , the slightly modified asymmetric mannich addition of alkyne to imine with cubf4(ch3cn)4 and nboclproline as catalysts was utilised ( scheme  2).15 the enantiomeric excesses of ( r)dimers 5 and 6 may reach>99  % from 9295  % after one recrystallisation procedure ( figures  s1 and s2 ) . the single crystal of ( r)dimer 5 was obtained by slow evaporation of ch2cl2/nhexane solution ( figure  1 ) . ( r , r , r)tetramers 10 and 11 were prepared from enantiopure deprotected dimer aldehyde and alkyne . in product 11 , the ( r , s , r)diastereomer was hardly detected by using hplc ( figure  2  a ) . moreover , ( r , r , r , r)pentamer 15 was prepared from 11 , and its ( r , r , r , s)diastereomer was also hardly detected ( figure  2  b ) . the asymmetric reaction based on enantiopure substrates gave the enantiopure allr products , whether the newly formed chiral carbon was located on the end or centre of the main chain . ( r , r , r , r , r)hexamer 16 and ( r , r , r , r , r , r , r)octamers 17 , 18 , and 20 were prepared by using a similar procedure.16 compound 19 was the detms product of 17 . the structures of the oligomers were confirmed by using nmr , ir and highresolution ms techniques . unfortunately , it was difficult to synthesise a longer oligomer , owing to the poor solubility of reaction substrates with five or more repeating units . 
  the singlecrystal structure of ( r)dimer 5 . the angle c13c12c9 : 110.35. crystal data for 1 : c33h35no4si ; mr=537.71 ; triclinic ; space group , p1 ; a=8.4991(9 )   , b=9.6789(10 )   , c=10.3917(10 )   ; =84.461(2) , =82.866(2) , =69.252(2).23 
  hplc analysis of a )  ( r , r , r)11 and b )  ( r , r , r , r)15 using chiralpak i d . eluent : nhexane / isopropanol / ch2cl2 ( v : v : v)=17.5:65:17.5 for ( r , r , r)11 , 0.2  ml  min ; isopropanol / ch2cl2 ( v : v)=60:40 for ( r , r , r , r)15 , 0.2  ml  min . the ( r , s , r ) and ( r , r , r , s ) diastereomers were prepared with nbocdproline as the catalyst . in the initial solubility test , we found that 3  wt  % 18 in ch2cl2 at room temperature formed a translucent fluid , which is characteristic of an lc phase . then , we used optical microscopy to evaluate whether all of the oligomer solutions form an lc phase or not . all of the samples in different solvents were prepared by heating the oligomers in a sealed tube at 90  c for 10  min , and then keeping them at room temperature for 2  h with slow stirring . the oligomer samples were drawn into microcapillaries and examined between crosspolarising filters at room temperature ( figure  3 ) . in general , the observation of birefringence is taken as evidence of lc phase formation.17 no birefringence was observed for concentrations of up to 5  wt  % 10 or 11 and up to 3  wt  % 15 , whereas only 2  wt  % 16 , 18 , and 20 , as well as 1  wt  % 17 and 19 in ch2cl2 displayed birefringence . different groups on the terminal alkyne [ si(ipr)3 , sime3 and h ] and the substitution of one nc8h17 group in the side chains did not affect lc phase formation . the smoky optical textures suggested the existence of a hexagonal lc phase.18 in contrast , 1620 in chcl3 , thf , dmf or dmso did not form an lc phase . notably , the diastereomers with one ( s)carbon , such as ( r , r , r , s , r , r , r)18 , also displayed good solubility and no birefringence . interestingly , 5  wt  % 15 in ch2cl2 can form a gel at room temperature ( figure  s3 ) . polarising optical microscope images of a )  11 , 5  wt  % ; b )  16 , 2  wt  % ; c )  17 , 1  wt  % ; d )  18 , 2  wt  % ; e )  19 , 1  wt  % ; f )  20 , 2  wt  % in ch2cl2 . if an lc phase is formed in cd2cl2 , the quadrupolar coupling between the d atoms gives rise to characteristic h  nmr line shapes.19 figure  4  b showed that the h  nmr spectra of 0.1  wt  % 18 in cd2cl2 gave a sharp single peak for the cd2cl2 resonance . in contrast , the h  nmr signal of 3  wt  % 18 in cd2cl2 was evidently broadened and a slight split was observed ( figure  4  a ) , indicating the existence of an lc phase . h  nmr spectra of a )  3  wt  % and b )  0.1  wt  % 18 in cd2cl2 at room temperature . we also performed powder xray diffraction ( pxrd ) experiments to characterise the microstructure of the assemblies . the solids of 1620 , prepared by slow evaporation of lc phases , gave similar pxrd patterns ( figure  5 ) , suggesting the same accumulation structure . take solid 18 as an example , seven diffraction peaks at d spacings of 1.70 , 1.00 , 0.88 , 0.66 , 0.58 , 0.51 and 0.46  nm with a ratio of 1:1/3 
 : 1/2:1/7 
 /:1/3:1/12 
 /:1/4 corresponded to a hexagonal columnar structure.20 the postulated accumulation model was similar to those previously described in the references.10 , 11 the helical hydrocarbon backbones stack atop one another along the same helix axis to form a long column , and seven long columns further assemble laterally . this possibly caused the accumulation structure to become partially destructed , because solvent molecules could take part in the assembly . so , it was reasonable that the acquired signal peaks became broadened . the ( 110 ) peak was relatively weak . fortunately , the ( 220 ) peak , characteristic of hexagonal accumulation , was clear . the strong diffraction peak at 0.38  nm could possibly be attributed to the screw pitch or the  stacking . in  situ measurement of the lc sample however , we also could discriminate the ( 100 ) , ( 110 ) and ( 200 ) peaks , because their relative positions are similar to those of solid samples . in particular , the diffraction peak at 0.38  nm that symbolises the screw pitch was very strong . interestingly , the pxrd pattern of xerogel 15 exhibited three peaks at d spacings of 2.32 , 1.15 and 0.77  nm , corresponding to a lamellar architecture with a reciprocal spacing ratio of 1:1/2:1/3 ( figure  6 ) . foldamer.6h 
  xrd patterns of the lc phase of 20  wt  % 18 in ch2cl2 and solids 1620 prepared by slow evaporation of lc phases in ch2cl2 at room temperature . the ( 100 ) , ( 110 ) , ( 200 ) , ( 210 ) , ( 300 ) , ( 220 ) and ( 400 ) peaks correspond to a hexagonal accumulation structure . the ( 100 ) , ( 200 ) and ( 300 ) peaks correspond to a lamellar structure . when lyotropic lc phases were formed from helical peptides , the formation of rodshaped assemblies was usually observed.7 g herein , scanning electron microscopy ( sem ) and transmission electron microscopy ( tem ) were also used to explore evidence of lc formation . the sem images of 1620 in the lc phase explicitly displayed many thin nanofibres ( figure  7 ) , indicating a typical lc microstructure . the sem and tem pictures of gel 15 also displayed many entangled nanofibres ( figures  7  a and 8  a ) . sem images of a )  xerogel 15 , and solids b )  16 , c )  17 , d )  18 , e )  19 , and f )  20 prepared from slow evaporation of lc phases . tem pictures of a )  gel 15 , and lcs b )  16 , c ) 17 , d )  18 , e )  19 and f )  20 . we also measured the ultraviolet ( uv ) absorption and circular dichroism ( cd ) spectra of these oligomers at different concentrations to further evaluate their assembly behaviours in solution . the uv spectra of 17 in ch2cl2 showed a maximum absorption at 311  nm , ascribed to pe and paminobenzoic ester chromophores ( figure  9  a ) . the cd spectra of 0.05  mm or 0.5  mm 
 17 in ch2cl2 showed the positive cotton effects in the range of 270320  nm ( figure  9  a ) . from 0 to 0.5  mm , the signal intensities were approximately linearly dependent on concentration . the uv and cd spectra of 15 , 16 , 18 , 19 , and 20 in dilute solutions were similar to those of 17 ( figures  9  b and s4s7 ) . notably , the molar absorption coefficients of 17 in some good solvents such as thf or dmso were almost the same as that in ch2cl2 , although the uv signals exhibited a slight shift and the amplitude of the cd signal also changed ( figure  10 ) . uv and cd spectra of a )  17 of 0.050.5  mm  ( dot ) , 4  mm  ( dash ) , 5  mm  ( solid ) ; b )  19 of 0.05  mm  ( dot ) , 0.5  mm  ( dash ) , 5  mm  ( solid ) in ch2cl2 at room temperature . the uv spectrum of 4  mm 
 17 at 270320  nm displayed noise . the cd spectrum of 4  mm 
 17 is not shown , because it only displayed strong noise . the uv and cd spectra of 0.05  mm 
 17 in ch2cl2  ( solid ) , thf  ( dash ) and dmso  ( dot ) at room temperature . the hypochromic effect , observed as the reduction in optical absorption intensity , is a powerful indicator of the oriented chromophores.4a hypochromic effects are sensitive to the distance , r , between chromophores and their relative orientations . figure  9  a shows that the absorbance value ( > 4 ) at 311  nm was out of measuring range when the concentration of 17 was 4  mm . interestingly , when the concentration of 17 reached the lc critical value of 5  mm ( ca . 1  wt  % ) , the absorption intensity abruptly decreased . this evident hypochromic effect can be explained by the formation of a compact helical backbone through intramolecular  stacking . the cd spectra of 5  mm 
 17 in ch2cl2 displayed very strong negative cotton effects at 330450  nm and a positive effect at 260320  nm . this was mainly attributed to the mppe backbone predominantly in one helical sense and consequent orderly arrangement of side chains . the change of cd signal to a larger amplitude is also attributed to the chiral cumulative effect or chiral amplification.21 the linear dichroism ( ld ) signals at the lc concentration are very weak ( figure  s8 ) , indicating that cd data are reliable . however , it was not possible to obtain the uv and cd spectra for 16 , 18 and 20 in the lc state , because the values of the critical concentration were high enough to surpass the measurement range . notably , when the lc phase of 17 was diluted 100  times , a strong bisignated cd signal was still observed and almost no change occurred for at least 2  weeks ( figures  11  a and s9 ) . the sem images of compound 17 , prepared from dilute solution , displayed many thin nanofibres ( figure  12  a ) . after the diluted sample was heated for 2  min at 100  c , the bisignated cd signal disappeared and the uv absorption was evidently strengthened ( figure  11  a ) , indicating that the foldamer in a random coil was recovered . similar phenomena were also observed for compound 19 ( figures  11  b and 12  b ) . furthermore , the dynamic light scattering ( dls ) experiments showed that the average hydrodynamic radius decreased after heating the dilute lc solution ( figure  13 ) . notably , dls experiments were not used to measure lc samples , because the concentrations were too high . in contrast , when the lc phases of oligomers 16 , 18 , and 20 were diluted , the cd spectra only presented patterns belonging to a random coil ( figure  s10 ) . in addition , the larger volume of tips groups on the terminal alkyne could affect the accumulation of these foldamer backbones and side chains . uv and cd spectra of diluted lc solution of a )  17 and b )  19 in ch2cl2 at room temperature before  ( solid ) and after  ( dot ) the samples were heated for 2  min at 100  c . sem images of assemblies of a )  17 and b )  19 on silicon chip prepared by fast casting a diluted lc solution in ch2cl2 ( 0.05  mm ) . dls diagrams of diluted lc solution of 17 in ch2cl2 : a )  before and b )  after heating . referring to the singlecrystal structure of ( r)dimer 5 ( figure  1 ) , there is an angle of approximately 110 between two adjacent pe segments in oligo(mppe)s . it is known that oligo(mpe ) has a helical turn of approximately six repeating units.11 , 22 we evaluated that a helix turn of more compact oligo(mppe)s could contain five repeating units , referring to molecular shapes of a dimer in the crystal and an intramolecular  stacking distance ( figures  14  a and 14  b ) . when aggregated schematic representation of a singlemolecular helical model [ side view  ( a ) ; top view  ( b ) ] , two adjacent long columns  ( c ) and the hexagonal accumulation model  ( d ) of octamer 17 . helical pitch : approximately 0.38  nm ; side chain length : 0.8  nm ; diameter of central channel : 1.5  nm ; distance between two adjacent long columns : 2.0  nm . these data were obtained according to xrd analysis , the crystal structure of dimer 5 and theoretical calculations . according to xrd data , there is a distance of approximately 2.0  nm between two adjacent long columns in the hexagonal structure . it could reasonably be assumed that long columns have a diameter close to cyclic mppe pentamer ( ca . moreover , the side chain has a length of 0.80.9  nm , according to crystal structure of ( r)dimer 5 . so , the superposition of side chains between adjacent long columns should exist ( figures  14  c and 14  d ) . this would improve contact in the aggregate , favouring the stabilisation of the whole hexagonal system . in contrast , there is almost no superposition between adjacent long columns in a hexagonal model of poly(mpe).11 notably , the thinnest fibre , with a diameter of approximately 6.5  nm in the tem images , almost matched the size of the smallest hexagonal aggregate unit ( figure  14  e ) . 
  the energy minimisation geometrical model of the cyclic mppe pentamer . geometry optimisation and the harmonic vibrational frequency model were performed at the b3lyp/321 g level using the gaussian  09 program package . the length of the mppe segment is approximately 0.88  nm , and the diameter of this pentamer is around 1.5  nm . we have successfully synthesised a series of simple chiral mppe oligomers with 4isopropoxycarbonyl phenylamino side groups . the construction of this novel mppe structure by using the asymmetric mannich addition approach is unprecedented . hexamer and octamers can form the hexagonal lyotropic lc phase in ch2cl2 , whereas the pentamer forms a lamellar gel . according to the experimental results and theoretical calculations , we clearly obtain a folding and further aggregating model . owing to the more compact backbone and more rigid side chain , the hexagonal aggregate is quite stable in ch2cl2 , although only weak van der waals interactions exist between long columns . foldamers . in our laboratory , the exploration for other types of mppe oligomers is underway . all reagents were obtained from commercial suppliers and , with the exception of ch2cl2 , were used without further purification . the h  nmr spectra were recorded at 400  mhz ( bruker av ) and the c  nmr spectra were recorded at 100  mhz with tms as the internal standard . optical rotation was measured by the perkinelmer 341  lc polarimeter , using the 10 or 1  cm optical rotation pool . sem was performed on an xl 30 scanning electron microscope ( micrion fei philips ) . a drop of the lc phase or a little gel was put on the glass sheet and dried in air at room temperature for 5  h. the sample was then coated with pt / pd in the ion coater for 40  s. tem images were obtained by using a jem1011 electron microscope operating at an acceleration voltage of 100  kv . a carboncoated copper grid was quickly put into the lc phase or gel for less than 1  s and dried in air at room temperature for 5  h. cd and ld spectra were obtained by using a biologic science mos450 scanning spectrometer . ld is the difference between absorption of light polarised parallel and polarised perpendicular to an orientation axis . pxrd measurements were carried out on a bruker d8 advance diffractometer , using cu  k radiation ( =0.154  nm ) . xray crystallographic analysis was performed on a bruker smart apex ii ccd diffractometer with graphitemonochromated mo  k radiation ( =0.71073   ) operated at 2.0 kw ( 50  kv , 40  ma ) . the structures were solved by using direct methods with the program shelxl97 and refined anisotropically through full matrix least squares with f 
  values and shelxl97 . aldehyde , alkyne , amine , cubf4(ch3cn)4 , tri(otolyl)phosphine , nboclproline and 3   molecular sieves ( ms ) powder were added into a dried roundbottomed flask . after the removal of the ms , the resulting green solution was diluted with ch2cl2 , washed with saturated aqueous nahco3 , dried over na2so4 , filtered , and concentrated under reduced pressure . the mixture was stirred for 5  h at 60  c in the sealed tube . the resulting suspension was washed with saturated aqueous nahco3 , dried over na2so4 , filtered , and concentrated under reduced pressure . the residue was purified by using silica gel column chromatography to afford the aldehyde product . the silaneprotected alkyne compound , thf , h2o and bf3et2o were added to a reaction tube . the mixture was stirred for 5  h at 60  c in the sealed tube . the resulting solution was washed with saturated aqueous nahco3 , dried over na2so4 , filtered , and concentrated under reduced pressure . the residue was purified by using silica gel column chromatography to afford the alkyne product . aldehyde , alkyne , amine , cubf4(ch3cn)4 , tri(otolyl)phosphine , nboclproline and 3   molecular sieves ( ms ) powder were added into a dried roundbottomed flask . after the atmosphere was replaced with nitrogen twice , after the removal of the ms , the resulting green solution was diluted with ch2cl2 , washed with saturated aqueous nahco3 , dried over na2so4 , filtered , and concentrated under reduced pressure . the mixture was stirred for 5  h at 60  c in the sealed tube . the resulting suspension was washed with saturated aqueous nahco3 , dried over na2so4 , filtered , and concentrated under reduced pressure . the residue was purified by using silica gel column chromatography to afford the aldehyde product . the silaneprotected alkyne compound , thf , h2o and bf3et2o were added to a reaction tube . the mixture was stirred for 5  h at 60  c in the sealed tube . the resulting solution was washed with saturated aqueous nahco3 , dried over na2so4 , filtered , and concentrated under reduced pressure . the residue was purified by using silica gel column chromatography to afford the alkyne product . as a service to our authors and readers , this journal provides supporting information supplied by the authors . such materials are peer reviewed and may be reorganized for online delivery , but are not copyedited or typeset . technical support issues arising from supporting information ( other than missing files ) should be addressed to the authors .
abstractthe motivation of foldamer chemistry is to identify novel building blocks that have the potential to imitate natural species . 
 peptides and peptide mimetics can form stable helical conformations and further selfassemble into diverse aggregates in water , where it is difficult to isolate a single helix . 
 in contrast , most  abiotic 
 foldamers may fold into helical structures in solution , but are difficult to assemble into tertiary ones . 
 it remains a challenge to obtain 
 abiotic 
 species similar to peptides . in this paper , a novel foldamer scaffold , in which pphenyleneethynylene units are linked by chiral carbon atoms , was designed and prepared . in very dilute solutions , 
 these oligomers were random coils . 
 the hexamer and octamers could form a hexagonal lyotropic liquid crystal ( lc ) in ch2cl2 when the concentrations reached the critical values . 
 the microscopic observations indicated that they could assemble into the nanofibers in the lc . 
 interestingly , after some lc phases were diluted at room temperature , the nanofibers could be preserved . 
 the good stabilities of the assemblies are possibly attributed to a more compact backbone and more rigid side chains .