Amidinium-carboxylate Salt Bridges Research Articles

Solvation-Enhanced Salt Bridges.

Salt bridges formed by amidines and carboxylic acids represent an important class of noncovalent interaction in biomolecular and supramolecular systems. Isothermal titration calorimetry was used to study the relationships between the strength of the interaction, the chemical structures of the components, and the nature of the solvent. The stability of the 1:1 complex formed in chloroform changed by 2 orders of magnitude depending on the basicity of the amidine and the acidity of the acid, which is consistent with proton transfer in the complex. Polar solvents reduce the stabilities of salt bridges formed with N,N'-dialkylamidines by up to 3 orders of magnitude, but this dependence on solvent polarity can be eliminated if the alkyl groups are replaced by protons in the parent amidine. The enhanced stability of the complex formed by benzamidine is due to solvation of the NH sites not directly involved in salt bridge formation, which become significantly more polar when proton transfer takes place, leading to more favorable interactions with polar solvents in the bound state. Calculation of H-bond parameters using density functional theory was used to predict solvent effects on the stabilities of salt bridges to within 1 kJ mol-1. While H-bonding interactions are strong in nonpolar solvents, and solvophobic interactions are strong in polar protic solvents, these interactions are weak in polar aprotic solvents. In contrast, amidinium-carboxylate salt bridges are stable in both polar and nonpolar aprotic solvents, which is attractive for the design of supramolecular systems that operate in different solvent environments.

Four- and two-armed hetero porphyrin dimers: their specific recognition and self-sorting behaviours

In this study we self-assembled the four-armed porphyrin hetero dimer capsule Cap4, stabilized through amidinium-carboxylate salt bridges, in CH2Cl2 and CHCl3. The dimer capsule Cap4 was kinetically and thermodynamically more stable than the corresponding two-armed dimer Cap2. The number of arms strongly influenced their recognition behaviour; guests possessing small aromatic faces (e.g., 1,3,5-trinitrobenzene) preferred residing in the cavity of the two-armed capsule Cap2, rather than in Cap4, both thermodynamically and kinetically; in contrast, large aromatic guests (e.g., 9,10-dibromoanthracene) were encapsulated predominantly by Cap4 because of favourable entropic effects. The number of arms enabled self-sorting behaviour of the dimer formation; complexation studies using an equimolar mixture of the four porphyrin constituents of the two capsules revealed the quantitative formation of the corresponding dimers Cap2 and Cap4. Furthermore, we examined the specific molecular recognition of Cap2 and Cap4; NMR experiments of mixtures of Cap2 and Cap4 in the presence of favourable guests for Cap2 and Cap4 revealed that these guest molecules were encapsulated selectively by their preferred hosts.

Recognition of dicarboxylic acids and diphosphonic acids using anthracene-based diamidine: formation of amidinium-carboxylate and amidinium-phosphonate salt bridges in a protic solvent

ABSTRACT The formation of a stable ‘amidinium-carboxylate’ salt bridge, even in a competing protic solvent (MeOH), was observed based on the binding experiments of anthracene-based diamidine (1) and dicarboxylic acids. The formation of 1:1 binding complexes of the diamidine 1 and dicarboxylic acids was confirmed by DOSY NMR, ESI-Mass, titration experiments and a single crystal X-ray analysis. Similarly, the formation of the ‘amidinium-phosphonate’ salt bridge in the MeOH solution was also evidenced by the complexation of the diamidine 1 and diphosphonic acids.

Complementary double-stranded helical oligomers bearing achiral bifunctional groups that catalyze asymmetric aldol reaction.

Two novel chiral dimer and trimer strands composed of m-terphenyl groups linked through p-diethynylbenzene units with the chiral amidine group and achiral piperazine group introduced at the terminus or center of the strands, respectively, and its complementary achiral carboxylic acid dimer and trimer were synthesized. The complementary chiral/achiral strands form an excess-handed double-helical structure as supported by intense split-type Cotton effects in the absorption regions of the conjugated backbones biased by the chiral amidinium-carboxylate salt bridges. The double-helical trimer was found to catalyze the direct aldol reaction of cyclohexanone with 4-nitrobenzaldehyde and produce the products with a moderate enantioselectivity despite the fact that the catalytically active bifunctional piperazine/carboxylic acid pair introduced in the middle is achiral, indicating the key role of the one-handed double-helical framework for supramolecular bifunctional organocatalysis.

Amidinium–carboxylate salt bridge mediated proton-coupled electron transfer in a donor–acceptor supramolecular system

A supramolecular polymer that allows for intrapolymer proton-coupled photoinduced electron transfer was constructed by means of amidinium-carboxylate salt bridges.

Chiral Template-Directed Regio-, Diastereo-, and Enantioselective Photodimerization of an Anthracene Derivative Assisted by Complementary Amidinium–Carboxylate Salt Bridge Formation

A series of optically active amidine dimers composed of m-terphenyl backbones joined by a variety of linkers, such as achiral and chiral p-phenylene and chiral amide linkers, were synthesized and used as templates for the regio- (head-to-tail (HT) or head-to-head (HH)), diastereo- (anti or syn), and enantioselective [4 + 4] photocyclodimerization of an achiral m-terphenyl-based carboxylic acid monomer bearing a prochiral 2-substituted anthracene at one end (1) through complementary amidinium-carboxylate salt bridges. The amidine dimers linked by p-phenylene linkages almost exclusively afforded the chiral syn-HT and anti-HH dimers at 25 °C, while those joined by amide linkers produced all four dimers. The p-phenylene-linked templates tended to enhance the syn-HT-photodimer formation at high temperatures with no significant changes in the product enantiomeric excess (ee), while the anti-HH-photodimer formation remarkably increased with the decreasing temperature accompanied by a significant enhancement of the product ee up to -86% at -50 °C. Temperature-dependent inversion of the chirality of the anti-HH dimer was observed when the chiral phenylene-linked amidine dimer was used and the product ee was changed from 22% at 50 °C to -86% at -50 °C. A similar enhancement of the enantioselectivity of the anti-HH dimer was also observed for the chiral amide-linked template, producing the anti-HH dimer with up to -88% ee at -50 °C. The observed difference in the regio-, diastereo-, and enantioselectivities due to the difference in the linker structures of the amidine dimers during the template-directed photodimerization of 1 was discussed on the basis of a reversible conformational change in the amidine dimers complexed with 1.

Cobalt(II)-Salen-Linked Complementary Double-Stranded Helical Catalysts for Asymmetric Nitro-Aldol Reaction

Double-helical, bimetallic chiral Co(II)-salen complexes stabilized by chiral amidinium–carboxylate salt bridges efficiently catalyzed the asymmetric nitro-aldol (Henry) reaction, producing products with up to an 89% enantiomeric excess (ee); the reactivity and enantioselectivity were higher than those catalyzed by the corresponding single strands. The key role of the chiral double-helical framework for the supramolecular bimetallic catalysis has been revealed by a double-helical catalyst carrying achiral Co(II)-salen units that promoted the Henry reaction, yielding the product with a 50%–45% ee, while the corresponding single strands showed poor or no enantioselectivity.

Chirality- and sequence-selective successive self-sorting via specific homo- and complementary-duplex formations.

Self-recognition and self-discrimination within complex mixtures are of fundamental importance in biological systems, which entirely rely on the preprogrammed monomer sequences and homochirality of biological macromolecules. Here we report artificial chirality- and sequence-selective successive self-sorting of chiral dimeric strands bearing carboxylic acid or amidine groups joined by chiral amide linkers with different sequences through homo- and complementary-duplex formations. A mixture of carboxylic acid dimers linked by racemic-1,2-cyclohexane bis-amides with different amide sequences (NHCO or CONH) self-associate to form homoduplexes in a completely sequence-selective way, the structures of which are different from each other depending on the linker amide sequences. The further addition of an enantiopure amide-linked amidine dimer to a mixture of the racemic carboxylic acid dimers resulted in the formation of a single optically pure complementary duplex with a 100% diastereoselectivity and complete sequence specificity stabilized by the amidinium–carboxylate salt bridges, leading to the perfect chirality- and sequence-selective duplex formation.

Supramolecular polymer gels formed from carboxy-terminated telechelic polybutadiene and polyamidine through amidinium-carboxylate salt bridge

In this article, we report the preparation and properties of the bulk supramolecular polymer gels prepared from a polybutadiene based on the amidinium-carboxylate salt bridge, highlighting the difference from a well-established network system based on carboxylic acid and amine. We have prepared the amidinium-carboxylate salt bridge-based supramolecular polymer gels from a carboxy-terminated telechelic polybutadiene and a linear polyamidine having N,N′-di-substituted acetamidine group in the main chain. FTIR analysis along with Small angle X-ray scattering measurements indicated that the salt bridge was attributed to the gelation through three-dimensional network formation. Virtually no fluidity was observed for the supramolecular gel containing equimolar amounts of the carboxyl group and the amidine group, which showed a high G′ value of about 1 MPa at room temperature and a Tgel of 37 °C. For comparison, the supramolecular polymer gels crosslinked by ammonium-carboxylate salt were prepared using a linear polyethyleneimine instead of the polyamidine. The gel with equimolar amounts of the carboxyl group and the secondary amino group showed liquid-like fluidity with a G′ value of about 0.01 MPa at room temperature, which was attributed to the fact that a certain amount of the carboxyl group remained as its free form without salt formation, as evidenced by FTIR analysis. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 1815–1824

Supramolecular Organogels Formed through Complementary Double-Helix Formation.

Optically active amidine ((R)-1) and achiral carboxylic acid (2) dimers with a m-terphenyl backbone linked by a 1,4-phenylene diacetylene unit form a double helix, (R)-1⋅2, through complementary amidinium-carboxylate salt bridges in THF. Upon the addition of poor solvents, such as n-hexane, the duplex forms an organogel as a result of supramolecular polymerization of the duplex by intermolecular rearrangement of the salt bridges. In sharp contrast, an analogous racemic duplex composed of achiral amidine residues and an optically active duplex linked by a shorter diacetylene unit with a higher binding affinity than that of (R)-1⋅2 does not show any gelation. The supramolecular fluorescent gels exhibit reversible thermo- and chemoresponsive behavior. The chiroptical properties of the gels, the mechanism of gelation, and the amplification of helical chirality during the gelation of (R)-1⋅2 in the absence and presence of its enantiomeric counterpart, (S)-1⋅2, and a racemic duplex, consisting of achiral amidine and carboxylic acid dimers, were investigated by following changes in the absorption and circular dichroism spectra.

Synthesis of helically twisted [1 + 1]macrocycles assisted by amidinium–carboxylate salt bridges and control of their chiroptical properties

A series of optically active, helically twisted [1 + 1]macrocycles connected via o-, m-, and p-linkages (o-, m-, and p-) was prepared from the corresponding linear duplexes stabilized by complementary amidinium-carboxylate salt bridges bearing two arms with terminal vinyl groups at both ends through the ring-closing metathesis reaction in the good yields of 67, 92, and 96%, respectively. The chiroptical properties of the macrocycles were dependent on the linker geometries and could be controlled by acid-base interactions and zinc coordination, the changes in which were detected by their CD and absorption spectral changes and fluorescence colors.

Four-component assembly in the crystalline state driven by amidinium–carboxylate salt bridge formation from an aqueous solution

A series of diamidine dihydrochlorides was prepared utilizing a spacer unit to control the distance between the two amidinium groups. The introduction of two amidinium groups to the 1,8-position of each spacer unit (i.e., 9,10-dihydroanthracene, anthracene, biphenylene) can control the direction of formation of a self-assembled structure. The fine-tuning of the distances between the two amidinium groups in the spacer units can help control the stabilizing interactions of two carboxylic acid units (intermolecular attraction) after the four-component assembly (see ). Based on this concept, we succeeded in the formation of a four-component box-like assembled structure using amidinium-carboxylate salt bridge formation in the crystalline state from aqueous solutions.

Photocontrolled template-directed synthesis of complementary double helices assisted by amidinium–carboxylate salt bridge formation

The template-directed imine-bond forming reactions between chiral amidines or achiral carboxylic acids monomers bearing a formyl or an amino group at one end were remarkably accelerated 34- or 10-fold in chloroform in the presence of the corresponding optically inactive carboxylic acid dimer or optically active amidine dimer linked by a trans-azobenzene unit as the template, respectively. The cis-azobenzene-linked carboxylic acid template markedly slowed the monomer conversions, and hence a reversible photocontrolled dimerization was achieved by light-induced cis–trans isomerization upon alternative irradiation with UV and visible light.

Thermodynamic and Kinetic Stabilities of Complementary Double Helices Utilizing Amidinium–Carboxylate Salt Bridges

A series of dimer strands consisting of m-terphenyl backbones bearing complementary chiral or achiral amidines and achiral carboxylic acid residues connected by various types of linkers, such as diacetylene, Pt(II)-acetylide, and p-diethynylbenzene linkages, were synthesized by a modular strategy, and their chiroptical properties on the complementary double helix formations were investigated by absorption, circular dichroism (CD), and (1)H NMR spectroscopies. The thermodynamic and kinetic stabilities of the complementary double helices assisted by amidinium-carboxylate salt bridges are highly dependent on their linkages, and the thermodynamic analyses of the dimer duplexes revealed that the association constants increased in the order: Pt(II)-acetylide linker < p-diethynylbenzene linker < diacetylene linker, which is in agreement with the reverse order of their bulkiness. The substituents on the amidine groups were also found to affect the stabilities on the duplexes and the association constants increased in the order: isopropyl < (R)-1-phenylethyl < cyclohexyl. In addition, the introduction of electron-donating and/or electron-withdrawing substituents at the phenyl groups of the p-diethynylbenzene linkers connecting the amidine and carboxylic acid units, respectively, tends to stabilize the complementary double helices, especially in polar solvents, such as DMSO, due to the attractive charge-transfer interactions between the aromatic linkers, although the salt bridge formation is hampered in DMSO. Furthermore, the kinetic analyses of the chain exchange reactions for the duplexes bearing diacetylene and p-diethynylbenzene linkages showed that these were slow processes with negative ΔS([symbol: see text]) values, meaning that the chain exchange reactions proceed via direct exchange pathways. In contrast, those for the duplexes bearing Pt(II)-acetylide linkages were fast processes supported by positive ΔS([symbol: see text]) values, suggesting that the chain exchange reactions proceed via dissociation-exchange ones. The helix-inversion kinetics investigated for the racemic dimer duplexes composed of achiral amidines based on variable-temperature (1)H NMR measurements indicated that the barriers for the helix-inversion increased in the order: Pt(II)-acetylide linker, p-diethynylbenzene linker < diacetylene linker.

Chiral amplification in double-stranded helical polymers through chiral and achiral amidinium–carboxylate salt bridges

A series of m-terphenyl-based random copolymers of chiral and achiral amidines, and their complementary homopolymers of achiral carboxylic acids were prepared by the copolymerization of a p-diiodobenzene derivative, with the diethynyl monomers containing a chiral or achiral amidine group and a carboxyl group using the Sonogashira coupling reaction. The obtained chiral/achiral amidine copolymers assembled into a double-stranded helical structure upon complexation with the complementary achiral homopolymer of carboxylic acids through interstrand amidinium−carboxylate salt bridges. The complexes exhibited characteristic induced cotton effects in the π-conjugated main-chain chromophore regions, indicating that the interstrand duplexes possess a preferred-handed double-helical structure. The effect of the chiral and achiral amidine contents on the amplification of the helical chirality (‘the sergeants and soldiers effect’) during the interstrand double-helix formation was investigated by comparing the cotton effect patterns and intensities of the duplexes with those of the corresponding all-chiral amidine-based double-helical polymer. m-Terphenyl-based random copolymers of chiral and achiral amidines and its complementary homopolymer of achiral carboxylic acids self-assembled to form complementary double helices with a preferred-handed helical sense via interstrand amidinium–carboxylate salt bridges, thus showing induced cotton effects in the π-conjugated main-chain chromophore regions. A unique amplification of the helical chirality (‘the sergeants and soldiers effect’) was, for the first time, observed during the double-helix formation.

アミジニウムーカルボキシレート塩橋形成を用いた新規キラル[2]カテナンの設計と合成およびその構造制御

アミジニウムーカルボキシレート塩橋形成を用いた新規キラル[2]カテナンの設計と合成およびその構造制御

Synthesis of Complementary Double-Stranded Helical Oligomers through Chiral and Achiral Amidinium−Carboxylate Salt Bridges and Chiral Amplification in Their Double-Helix Formation

A series of complementary molecular strands from 2-mer to 5-mer that are composed of m-terphenyl units bearing chiral/achiral amidine or achiral carboxyl groups linked via Pt(II) acetylide complexes were synthesized by sequential stepwise reactions, and their chiroptical properties on the double-helix formation were investigated by circular dichroism (CD) and (1)H NMR spectroscopies. In CHCl(3), the "all-chiral" amidine strands consisting of (R)- or (S)-amidine units formed preferred-handed double helices with the complementary achiral carboxylic acid strands through the amidinium-carboxylate salt bridges, resulting in characteristic induced CDs in the Pt(II) acetylide complex regions, indicating that the chiral substituents on the amidine units biased a helical sense preference. The Cotton effect patterns and intensities were highly dependent on the molecular lengths. The complementary double-helix formation was also explored using the chiral/achiral amidine strands with different sequences in which a chiral amidine unit was introduced at the center (center-chiral) or a terminus (edge-chiral) of the amidine strands. The effect of the sequences of the chiral and achiral amidine units on the amplification of chirality (the "sergeants and soldiers" effect) in the double-helix formation was investigated by comparing the CD intensities with those of the corresponding all-chiral amidine double helices with the same molecular lengths. Variable-temperature CD experiments of the all-chiral and chiral/achiral amidine duplexes demonstrated that the Pt(II)-linked complementary duplexes are dynamic and their chiroptical properties including the chirality transfer from the chiral amidine unit to the achiral amidine ones are significantly affected by the molecular lengths, sequences, and temperatures. On the basis of the above results together with molecular dynamics simulation results, key structural features of the Pt(II)-linked oligomer duplexes and the effect of the chiral/achiral amidine sequences on the amplification of chirality are discussed.

カチオン-π相互作用を用いた極性溶媒中でのアミジニウム－カルボキシレートの安定化,

カチオン-π相互作用を用いた極性溶媒中でのアミジニウム－カルボキシレートの安定化,

Amidinium Carboxylate Salt Bridges as a Recognition Motif for Mechanically Interlocked Molecules: Synthesis of an Optically Active [2]Catenane and Control of Its Structure

Amidinium Carboxylate Salt Bridges as a Recognition Motif for Mechanically Interlocked Molecules: Synthesis of an Optically Active [2]Catenane and Control of Its Structure

Amidinium Carboxylate Salt Bridges as a Recognition Motif for Mechanically Interlocked Molecules: Synthesis of an Optically Active [2]Catenane and Control of Its Structure

Salty catenane: An optically active [2]catenane was synthesized by utilizing an amidinium carboxylate salt bridge (see picture). The relative motion of the two macrocyclic components was completely controlled by an acid/base or Zn2+/cryptand couple.