“Sticky”-Ends-Guided Creation of Functional Hollow Nanopores for Guest Encapsulation and Water Transport

Abstract

Commercial uses of water-transporting aquaporins for seawater desalination and wastewater reclamation/reuse are being investigated in both academia and the industry. Presently, structural complexity, stability, scalability, and activity reconstitution of these costly channel proteins still present substantial challenges to scientists and engineers. An attractive strategy is to develop robust synthetic water channels able to mimic the water-transporting function of aquaporins for utility in the making of next generation of water channel-based biomimetic porous membranes for various water purification applications. In sharp contrast to burgeoning development in constructing synthetic ion channels over the past four decades, very limited progress has been made in the area of synthetic water channels. A handful of such examples include the first report by Percec in 2007 (Percec et al. J. Am. Chem. Soc. 2007, 129, 11698-11699), which was followed by Barboiu in 2011 (Barboiu et al. Angew. Chem., Int. Ed. 2011, 50, 11366-11372), Gong and Hou in 2012 (Gong et al. Nat. Commun. 2012, 3, 949; Hou et al. J. Am. Chem. Soc. 2012, 134, 8384-8387), and Zeng in 2014 (Zeng et al. J. Am. Chem. Soc. 2014, 136, 14270-14276). Radically deviating from the fact that the discovery of novel synthetic channel systems with desired transport selectivity is most often empirical and very often serendipitous, we have instead adopted a more rational designer approach whereby molecular building blocks have been carefully designed from scratch to perform their intended built-in functions. Our designer journey started in 2008, two years after I started leading a group at the National University of Singapore. Since then, we have been actively investigating the use of designed water-binding "aquafoldamers" to construct synthetic water channels for the rapid and selective transport of water molecules ideally with the exclusion of all other nonproton molecular species. Toward this goal, we designed and characterized, by an experimental-theoretical synergy, a new class of modular, H-bonded, and crescent-shaped oligopyridine amide foldamers, enclosing a sizable cavity of about 2.8 Å in diameter. Matching well with the diameter of water molecules and decorated by interior-pointing H-bond donors (amide H atoms) and acceptors (pyridine N atoms) for water binding, this sizable cavity experimentally proves to be suitable for water recognition. In particular, helically folded oligomers are found to be capable of binding two water molecules that are vertically aligned in parallel with helical axis. However, the existence of two repulsive groups at the two helical ends prevents the formation of 1D hollow tubular cavity, via self-assembly, for encapsulating 1D water chains. Subsequently, we introduced two electrostatically complementary functional groups that act as "sticky" ends at helical ends. These feeble "sticky" ends faithfully and seamlessly align short cavity-containing helices one-dimensionally to create hollow tubular aquapores. To our delight, these aq...

Fluorescent Short‐Stranded Helical Foldamers Based on L‐shaped Dibenzopyrrolo[1,2‐a][1,8]naphthyridine

“…m-Phenylene-bridged dimer 14 was obtained in 25 % yield through regioselective Suzuki-Miyaura cross-coupling at the 2-positions of dibromides 12 with m-phenylene spacer unit 13 and subsequentd ebrominations at the 5,5'-positions by using Zn/NH 4 Cl. Regioselective Suzuki-Miyaura cross-coupling only at the 9,9'-positions of 4,4',9,9'-tetrakis(pivaloyloxy- Scheme1.Synthesis of p-spacer-bridged dimers 1-3.Reagents and conditions:i )NBS (1.5 equiv), CH 3 CN, 25 8C, 1.5 h, 79 %; ii)a)danB-Bpin(2.0 equiv), Pd 2 (dba) 3 (2 mol %), KOAc (6.0 equiv),1 ,4-dioxane, 100 8C, 2d;b )conc. HCl/ THF = 1:4, 25 8C, 2d,6 6% over two steps;iii) 8,Pd(PPh 3 ) 4 (3 mol %), 2 m K 2 CO 3 aq./1,4-dioxane = 1:3, 100 8C, 1d,2 5%;i v) 9,K 3 PO 4 (2.4 equiv), Pd(OAc) 2 (4 mol%), S-Phos (11mol %), toluene,1 10 8C, 2d,5 6%;v )10,K 3 PO 4 (2.4 equiv), Pd(OAc) 2 (4 mol %), S-Phos (7 mol %), toluene, 110 8C, 1d,7 6%.…”

“…Interestingly,t he 1 HNMR study of dimer 1 in variouss olvents revealed that dimer 1 retainedi ts helical conformation regardless of solvent polarity (Figure 7), although it is known that the conformationo ft ypical foldamersu tilizing hydrogen bonds [3][4][5] and the solvophobic effect [2,9] is sensitive to the solvent polarity.A sm entioned above, the biphenylylene-bridged dimer 1 preferentially adopted ah elical form in CDCl 3 while having ar elatively flexible spacer (Figure 6b and Figure 7b). In either 3:2( v/v) CDCl 3 /n-hexane or 3:1( v/v) CDCl 3 /CD 3 OD, the H B and H C proton signals of the quinoliner ing shifted to more upfield positions (Figure 7a and cv s. b).…”

“…Synthetic helical foldamers, [1][2][3][4][5][6][7][8][9][10] which fold into ah elical form from random coils spontaneously or in response to stimuli, have attracted attentionf or use as peptidem imetics, selective guest recognition, stimuli-responsive supramolecules, and chiral recognition.F or flexible foldamers,ahelical conformation is not alwaysf avored because ad ecrease in flexibility can lead to entropyloss. Thus, mostarene-based foldamers use enthalpicallyf avorable interactions, such as hydrogen bonds, [3][4][5] solvophobic effects, [2,6,9] and guest binding [7,10] in addition to p-p stacking to promote ah elical conformation from a random coil. In this context, curved and rigid arene units [5] would be promising candidates to constructe ntropically favorable helical foldamers with am inimal number of units and rotatable bonds per one turn compared with conventionalm ultiunit type helical foldamers.…”

“…In this context, curved and rigid arene units [5] would be promising candidates to constructe ntropically favorable helical foldamers with am inimal number of units and rotatable bonds per one turn compared with conventionalm ultiunit type helical foldamers. Furthermore, rigid polycyclic arenebased foldamers [3][4][5][6][7][8] would have attractive functionalities such as color tuning, fluorescence, p-conjugation, electron-or holetransport, ion-channels,a nd switching control. [4c, 7d, 8] However,o nly al imited number of highly fluorescent helical foldamersh ave been reported, [10] despite their promise as an organic CPL (circularly polarizedl uminescence) emitter, [11] because of nonradiatived ecay owing to their flexibility around rotatable parts, and fluorescence weakening derived from intramolecular charget ransfer (CT) or excimer formation.…”

Macrocyclic shape-persistency of cyclo[6]aramide results in enhanced multipoint recognition for the highly efficient template-directed synthesis of rotaxanes

“…8 In all these cases, the “wheels” employed are based on macrocyclic molecules that are nonplanar and fairly flexible conformationally. In recent years, shape-persistent macrocycles, with noncollapsible and geometrically well-defined skeletons, such as phenylacetylene macrocycles, 9 have attracted considerable attention due to their intriguing functions, including supramolecular gelation, 10 channelized transportation, 11 organic catalysis, 12 molecular recognition 13 and multifunctional self-assembly. 14 Many shape-persistent macrocycles have well-defined surface topography and nanosized cavities with preorganized binding sites, and thus may exhibit enhanced complexation.…”