Anion and carboxylic acid binding to monotopic and ditopic amidopyridine macrocycles

Binding of inorganic anions, carboxylic acids, and tetraalkylammonium carboxylates by macrocyclic compounds of different size was studied by NMR in DMSO-d6. It has been shown that at least a 15-membered ring is necessary for successful recognition of fluoride. Larger macrocycles were shown to bind HSO4(-), H2PO4(-), Cl(-), and carboxylic acid salts. Effects of binding topicity are discussed. The 30-membered macrocycles 4 and 4m selectively bind substrates that are size- and shape-complementary: maximum binding is observed for dicarboxylic acids and dicarboxylates with four-carbon chains, and the binding constant for association of fumaric acid and 4 is ca. 5 orders of magnitude higher than that of maleic acid. The 30-membered macrocycle 4m showed selectivity toward alpha-ketocarboxylic acids. Secondary amino groups were not crucial for binding of fluoride to the macrocycles; however, they proved to be very important for selectivity and strength of carboxylic acid binding. The X-ray structure of the adduct of 4 and nitrobenzoic acid confirmed the guest H-bonding with both the amide and the secondary amino groups of the 30-membered macrocyclic host.     

Neutral metallomacrocycles with four or ten (PEt3)Pd(II) centers

The reaction of [(Et(3)P)PdCl(2)](2) with 2,3-dihydroxypyridine, 5-chloro-2,3,-dihydroxypyridine, or 2-hydroxynicotinic acid in the presence of base gives neutral, metallomacrocyclic compounds in which the heterocycles act as dianionic, bridging ligands. The macrocycles contain four or ten palladium atoms as evidenced by single crystal X-ray analyses.     

Cooperative Self‐Assembly of Pyridine‐2,6‐Diimine‐Linked Macrocycles into Mechanically Robust Nanotubes

Nanotubes assembled from macrocyclic precursors offer a unique combination of low dimensionality, structural rigidity, and distinct interior and exterior microenvironments. Usually the weak stacking energies of macrocycles limit the length and mechanical strength of the resultant nanotubes. Imine‐linked macrocycles were recently found to assemble into high‐aspect ratio (>10³), lyotropic nanotubes in the presence of excess acid. Yet these harsh conditions are incompatible with many functional groups and processing methods, and lower acid loadings instead catalyze macrocycle degradation. Here we report pyridine‐2,6‐diimine‐linked macrocycles that assemble into high‐aspect ratio nanotubes in the presence of less than 1 equiv of CF₃CO₂H per macrocycle. Analysis by gel permeation chromatography and fluorescence spectroscopy revealed a cooperative self‐assembly mechanism. The low acid concentrations needed to induce assembly enabled nanofibers to be obtained by touch‐spinning, which exhibit higher Young's moduli (1.33 GPa) than many synthetic polymers and biological filaments. These findings represent a breakthrough in the design of inverse chromonic liquid crystals, as assembly under such mild conditions will enable the design of structurally diverse and mechanically robust nanotubes from synthetically accessible macrocycles.     

Design and Synthesis of Polyoxazole‐based Macrocycles Tethered with a Phosphonate Group

We present the design and synthesis of polyoxazole‐based macrocycles containing a phosphonate group. A reliable route was established that allows for convenient and versatile incorporation of various phosphonate functionalities such as phosphonate ester, acid, and salt at the macrocyclic ring periphery. Such unprecedented macrocyclic compounds are anticipated to be appealing candidates as telomerase inhibitors.     

Synthesis, structures and reactivity of macrocyclic imidazolylboranes

New macrocyclic imidazolylboranes [imidazolylB(R¹)₂]_n, where selected carbon atoms of imidazolyl rings may bear substituents other than hydrogen, and where n=4 or 5, are obtained from 1-trimethysilylimidazoles and haloboranes XB(R¹)₂ by boron/silicon exchange using 2-bromoimidazole and benzimidazole. These macrocycles are formally zwitterionic and contain imidazolyl rings linked through their nitrogen atoms by BH₂, B(R¹)₂ or BR¹X units. Despite the sterical demand of these derivatives tetrameric macrocycles are formed. A new synthetic strategy to macrocyclic imidazolylboranes includes the preparation and cyclization of bis(imidazolyl)boronium chlorides. In addition dihaloboranes have been tested for cyclization to yield halogen-containing macrocycles. The new compounds are spectroscopically characterized and X-ray structure analyses of tetrameric- (2a) and pentameric 1-imidazolylborane (2a′), tetrameric 1-imidazolyldimethylborane (2b), tetrameric 1-(2-bromo)imidazolylborane (2d) and bis(2-bromoimidazolyl)boronium chloride (3d) are reported.     

Synthetic macrocyclic receptors in chiral analysis and separation

Chiral synthetic macrocyclic receptors that can achieve chiral discrimination by NMR spectroscopy and/or chiral separation by HPLC are overviewed. Synthetic macrocycles introduced here include crown ethers, calixarenes/calixresorcinarenes/calixpyrroles, macrocyclic amides/amines, and porphyrins. These macrocyclic frameworks are advantageous because intermolecular interactions can take place effectively, such as the ion–dipole interactions in crown ethers, the CH/π and π–π interactions in calixarenes, hydrogen bonding and salt formation in macrocyclic amides and amines, and π–π stacking and metal coordination in porphyrins. Additional functional groups on the periphery of the macrocyclic platforms not only make the whole molecule chiral but also act as the interaction sites. Chiral macrocyclic receptors can show a high degree of chiral recognition/discrimination by using the peripheral functional groups as well as the macrocyclic skeletons (preorganization). Both hosts and guests are shown in the figures to quickly overview the molecular recognition scope of synthetic macrocyclic receptors in chiral analysis and separation.     

Synthesis and self-association properties of diethynylbenzene macrocycles

We synthesized diethynylbenzene macrocycles (DBMs), cyclic oligomers of diethynylbenzene, having functional groups in the periphery of the macrocyclic framework and investigated their self-association properties in solution resulting from π-π stacking interaction. The tetrakis-DBM having hexadecyl ester groups showed dimerization behavior not only in chloroform-d, but also in o-dichlorobenzene-d₄.     

Non-template synthesis of ‘N4’ di- and tetra-amide macrocylic ligands with variable ring sizes

Nine new macrocyclic ligands containing two- or four-amide groups have been prepared by the cyclization reaction of three different diamines with acid chlorides (oxalyl dichloride or malonyl dichloride), diesters (diethyl oxalate or diethyl malonate) or 1,2-dichloroethane. The macrocycles prepared are four tetraaza-14-crown-4, four tetraaza-15-crown-4 and one tetraaza-16-crown-4. All the macrocyclic ligands were characterized by elemental analysis and, IR, UV, NMR and mass spectral investigations.     

One-pot synthesis of hybrid macrocyclic pentamers with variable functionalizations around the periphery

Rather than four- or six-residue macrocylces, one-pot macrocyclization allows for the highly selective formation of five-residue macrocycles rigidified by intramolecular hydrogen bonds. Variable functionalizations around the pentameric periphery were achieved by reacting monomers with higher oligomers bearing different exterior side chains. The formation of these hybrid pentamers suggests a chain-growth mechanism for the one-pot macrocyclization where the successive addition of monomers onto higher oligomers is faster than those between two monomers or two higher oligomers.     

Chiral macrocycles,part II: Transport of amino acid Li+ salts

Complexation of amino acids in both their zwitterionic and Li⁺ salt forms by macrocycles, and carrier-mediated transport of the Li⁺ salts through a CH₂Cl₂ membrane have been investigated: the transport study of four amino acids by a new series of tetrapyrazolic macrocycles with functionalized sidearms shows wide variations of the transport rates depending on both the macrocyclic sidearm and the amino acid structure.     

β‐Octamethoxy‐Substituted 22π and 26π Stretched Porphycenes: Synthesis,Characterization, Photodynamics,and Nonlinear Optical Studies

Three meso‐expanded tetrapyrrolic aromatic macrocycles, including 22π and 26π acetylene–cumulene bridged stretched octamethoxyporphycenes and octamethoxy[22]porphyrin‐(2.2.2.2), are reported, for the first time, by modification of previously reported synthetic methods. This strategy led to an enhancement in the overall yield of their corresponding octaethyl analogues. The methoxy‐substituted expanded porphycenes display slightly blueshifted absorption relative to their ethyl analogues, along with very weak fluorescence, probably due to efficient intramolecular charge transfer (ICT). Additionally, the two‐photon absorption (TPA) cross sections of these macrocycles were evaluated; these are strongly related to core expansion of the porphyrin aromaticity through increased meso‐bridging carbon atoms as well as conformational flexibility and substitution effects at the macrocyclic periphery. In particular, the octamethoxy stretched porphycenes display strong TPA compared with the octaethyl analogues due to the dominant ICT character of methoxy groups with a maximum TPA cross section of 830 GM at 1700 nm observed for 26π‐octamethoxyacetylene–cumuleneporphycene.     

Synthesis and retrostructural analysis of libraries of AB3 and constitutional isomeric AB2 phenylpropyl ether-based supramolecular dendrimers

We report the synthesis of methyl esters of 3-(4-hydroxyphenyl)propionic, 3-(3,4-dihydroxyphenyl)propionic, 3-(3,5-dihydroxyphenyl)propionic, and 3-(3,4,5-trihydroxyphenyl)propionic acids and their use in a convergent iterative strategy to prepare up to four generations of three libraries, one of 3,4,5- and two of constitutional isomeric 3,4- and 3,5-substituted 3-phenylpropyl dendrons. Each library contains 3-[3,4,5-tris(dodecyl-1-oxy)phenyl]propyl-, 3-[3,4-bis(dodecyl-1-oxy)phenyl]propyl-, 3-{3,4-bis[3-(4-dodecyl-1-oxyphenyl)propyl-1-oxy]phenyl}propyl-, and 3-{3,4,5-tris[3-(4-dodecyl-1-oxyphenyl)propyl-1-oxy]phenyl}propyl ether first-generation dendrons on their periphery and -CO2CH3, -COOH, and -CH2OH groups at their apex. Regardless of their generation number and their periphery, internal, and apex structures, these dendrons self-assemble into supramolecular dendrimers that self-organize into all periodic and quasi-periodic assemblies encountered previously and in several unencountered with architecturally related benzyl ether-based supramolecular dendrimers. A variety of porous columnar lattices that were previously obtained only from dendritic dipeptides and hollow supramolecular spheres were also discovered from these building blocks. The more flexible and less compact 3-phenylpropyl ether repeat units are stable under acidic conditions, facilitate a simpler synthetic strategy, provide faster dynamics of self-assembly into higher-order supramolecular structures of larger dimensions, exhibit lower transition temperatures than the corresponding benzyl ether homologues, and demonstrate the generality of the self-assembly concept based on amphiphilic dendrons.     

Preparation of a variety of macrocyclic Di- and tetraamides and their peraza-crown analogs using the crab-like cyclization reaction

Twelve new macrocyclic di- and tetraamides have been synthesized from the reaction of a bis(α-chloroamide) with a primary amine or with a diamine. Some of these cyclic di- and tetraamides contained pendant aminoalkyl groups attached on one or more ring nitrogen atoms. Two macrocyclic dithiadiamides were prepared from the reaction of a bis(α-chloroamide) and a dimercaptan. In every case, 12-, 14- and 15-membered cyclic di- and tetraamides were isolated in good yields. The 9-, 17- and 18-membered macrocycles were prepared in lower yields. Four of the amide-containing macrocycles were reduced by diborane to the perazacrown compounds.     

Synthesis of bis(indolylmaleimide) macrocycles

The synthesis of a novel class of macrocyclic bis(indolylmaleimides) is reported. The key step involves the intermolecular connection of 2,2′‐bridged indoles with 3,4‐dibromo‐2,5‐dihydro‐1H‐2,5‐pyrroledione (dibromomaleimide) derivatives. The bis(indolylmaleimides) afforded by this method were further processed by intramolecular nucleophilic substitution of the remaining bromo substituents forming flexible N‐substituted macrocycles ( 9a‐9j, 10a‐10e ) and, by connecting both maleimides, semi rigid macrocycles ( 7a‐7xx ).     

Rapid generation of macrocycles with natural-product-like side chains by multiple multicomponent macrocyclizations (MiBs)

A small parallel library of peptoid macrocycles with natural-product-derived side chains of biological importance was produced by Ugi-type multiple multicomponent macrocyclizations including bifunctional building blocks (Ugi-MiBs). Diverse exocyclic elements of high relevance in natural recognition processes, i.e., all functional amino acid residues (e.g., Cys, Arg, His, Trp) and even sugar moieties, can be introduced in a one-pot process into different types of peptoid-containing macrocyclic skeletons. This is exemplified by the use of a diamine/diisocyanide combination of Ugi-MiBs and N-protected alpha-amino acids or carboxy-functionalized carbohydrates as source for the natural-product-like exocyclic elements. Employed as the acid components of the multiple Ugi reactions, they appear as N-amide substituents on the macrocyclic cores. The use of different diamines and diisocyanides allows an easy variation of the N- to C-directionality and therefore of the position of the exocyclic elements.     

Macrocyclic bisbinaphthyl fluorophores and their acyclic analogues: signal amplification and chiral recognition

A series of optically active macrocyclic and acyclic bisbinaphthyls have been synthesized and characterized. The structure of one of the bisbinaphthyl macrocycles has been established by a single-crystal X-ray analysis. The UV and fluorescence spectra of these chiral compounds in various solvents and at different concentrations are studied. Formation of excimers is observed for the macrocyclic bisbinaphthyl compounds. Introduction of conjugated substituents to the 6,6'-positions of the binaphthyl units in the macrocycles leads to greatly amplified fluorescence signals. Using the 6,6'-substituted bisbinaphthyl macrocycles in place of the unsubstituted macrocycles allows a 2 orders of magnitude reduction in the sensor concentration for the fluorescence measurements. These macrocycles have exhibited highly enantioselective fluorescent enhancements in the presence of chiral alpha-hydroxycarboxylic acids and N-protected alpha-amino acids. They are useful as fluorescent sensors for chiral recognition. The macrocycles show much greater enantioselectivity in the substrate recognition than their acyclic analogues.     

Short synthesis of diamide-linked sucrose macrocycles

A convenient route to macrocyclic diamide-linked macrocyclic derivatives with a sucrose scaffold is presented. Reaction of sucrose based amines (o- and m-) with acid dichlorides afforded the monomeric macrocycles in excellent yields, while reaction of the p-amines also provided dimeric products.     

Enantiopure Laterally Functionalized Alleno–Acetylenic Macrocycles: Synthesis,Chiroptical Properties,and Self‐Assembly in Aqueous Media

A family of shape‐persistent alleno–acetylenic macrocycles (SPAAMs), peripherally decorated with structurally diverse pendant groups, has been synthesized and characterized in enantiomerically pure form. Their electronic circular dichroism (ECD) spectra feature a strong chiroptical response, which is more than two times higher than for open‐chain tetrameric analogues. A water‐soluble oligo(ethylene glycol)‐appended SPAAM undergoes self‐assembly in aqueous solution. Morphology studies by cryogenic transmission electron microscopy (cryo‐TEM) revealed the formation of aggregates with fibrous fine structures that correspond to tubular, macrocyclic stacks.     

Nickel(II) cyclidenes with appended ethylpyridine receptor centers as molecular tweezers for dicarboxylic acids

A series of 14-, 15-, and 16-membered nickel(II) cyclidene macrocycles appended with 2-aminoethyl(2-pyridine) receptors I-III, respectively, were prepared and characterized by X-ray crystallography and NMR techniques. The 14- and 15-membered macrocycles I and II exist in a planar or extended Z-configuration, whereas the 16-membered macrocycle III was saddle shaped and had two asymmetric configurations in the unit cell (IIIa in a "capped" configuration and IIIb in an "open" configuration). Variable-temperature (1)H NMR studies of III in CD(3)CN were conducted (25-65 degrees C), and at room temperature, the interconversion between capping and uncapping is slow on the NMR time scale, resulting in a broad spectrum, whereas at 65 degrees C, interconversion was fast. (1)H NMR binding studies indicated I-III bind unsaturated dicarboxylic acids in a 1:1 stoichiometry with binding constants approaching 400 M(-)(1) in CD(3)CN, and the binding strength was dependent on the shape of the macrocyclic cyclidene platforms, whereas monocarboxylic acids were not bound. Generally, the planar 14-membered cyclidene I bound diacids the weakest and the 16-membered cyclidene III bound diacids the strongest. The presence of nuclear Overhauser effect spectrometry cross peaks in a 20 mM solution of 1:1 II-maleic acid indicates that the binding mode is ditopic with the guest being encapsulated by the aminoethylpyridine arms above the macrocyclic framework.     

Efficient proton-templated synthesis of 18- to 38-membered tetraimino(amino)diphenol macrocyclic ligands: structural features and spectroscopic properties

A whole range of Robson-type tetraiminodiphenol macrocyclic ligands have been prepared as their perchlorate salts [H4L](ClO4)2 in high yield (ca. 90%) by a single-step [2 + 2] condensation reaction between 4-methyl(or tert-butyl)-2,6-diformyl(or diacyl)phenols and alpha,omega-diaminoalkanes (C2-C12) in the presence of acetic acid and NaClO4. The reduction of these 18- to 38-membered macrocyclic salts with NaBH4 have afforded corresponding tetraaminodiphenol macrocycles H2L'. The X-ray crystal structures of two of the tetraiminodiphenol macrocycles with the C2 and C4 lateral chains have been determined, and the optimized configurations for all of the macrocycles have been obtained by molecular mechanics calculations. The macrocycles have been characterized by elemental analysis and by IR, absorption, emission, and NMR spectroscopic study. The protonated tetraiminodiphenol macrocycles exhibit strong fluoroscence in methanol, acetonitrile, and nitromethane and undergo quenching when treated with triethylamine. The neutral macrocycles H2L, isolated by treating [H4L](ClO4)2 with excess of triethylamine, lack luminescence, as do the reduced tetraaminodiphenol macrocycles H2L'. The hydrolytic cleavage of [H4L](ClO4)2 has been studied.