Diffusion NMR spectroscopy in supramolecular and combinatorial chemistry: an old parameter--new insights

Intermolecular interactions in solution play an important role in molecular recognition, which lies at the heart of supramolecular and combinatorial chemistry. Diffusion NMR spectroscopy gives information over such interactions and has become the method of choice for simultaneously measuring diffusion coefficients of multicomponent systems. The diffusion coefficient reflects the effective size and shape of a molecular species. Applications of this technique include the estimation of association constants and mapping the intermolecular interactions in multicomponent systems as well as investigating aggregation, ion pairing, encapsulation, and the size and structure of labile systems. Diffusion NMR spectroscopy can also be used to virtually separate mixtures and screen for specific ligands of different receptors, and may assist in finding lead compounds.     

On the characterization of dynamic supramolecular systems: a general mathematical association model for linear supramolecular copolymers and application on a complex two-component hydrogen-bonding system

A general mathematical model for the characterization of the dynamic (kinetically labile) association of supramolecular assemblies in solution is presented. It is an extension of the equal K (EK) model by the stringent use of linear algebra to allow for the simultaneous presence of an unlimited number of different units in the resulting assemblies. It allows for the analysis of highly complex dynamic equilibrium systems in solution, including both supramolecular homo- and copolymers without the recourse to extensive approximations, in a field in which other analytical methods are difficult. The derived mathematical methodology makes it possible to analyze dynamic systems such as supramolecular copolymers regarding for instance the degree of polymerization, the distribution of a given monomer in different copolymers as well as its position in an aggregate. It is to date the only general means to characterize weak supramolecular systems. The model was fitted to NMR dilution titration data by using the program Matlab, and a detailed algorithm for the optimization of the different parameters has been developed. The methodology is applied to a case study, a hydrogen-bonded supramolecular system, salen 4+porphyrin 5. The system is formally a two-component system but in reality a three-component system. This results in a complex dynamic system in which all monomers are associated to each other by hydrogen bonding with different association constants, resulting in homo- and copolymers 4n5m as well as cyclic structures 6 and 7, in addition to free 4 and 5. The system was analyzed by extensive NMR dilution titrations at variable temperatures. All chemical shifts observed at different temperatures were used in the fitting to obtain the DeltaH degrees and DeltaS degrees values producing the best global fit. From the derived general mathematical expressions, system 4+5 could be characterized with respect to above-mentioned parameters.     

Counterion-dependent proton-driven self-assembly of linear supramolecular oligomers based on amino-calix[5]arene building blocks

Self-assembly of a calix[5]arene bearing a 12-aminododecyl pendant group on the lower rim into supramolecular oligomers through intermolecular iterative inclusion events is readily triggered by contact with acid solutions and is reversed to the amino monomer precursor by treatment with a base. 1H NMR data are consistent with the formation of head-to-tail assemblies derived from endo-cavity inclusion of the alkylammonium moiety. Diffusion NMR and light-scattering studies provide evidence for the presence of oligomers in solution and show that different counterions and concentrations result in different oligomer sizes, whereas ESI-MS and SEM investigations, respectively, indicate that self-assembly also takes place in the gas phase and in the solid state. The growth of these supramolecular oligomers is concentration-dependent; however, as a consequence of the saline nature of the monomer, it also shows a distinct counterion-dependence owing to ion-pairing/solvation effects.     

Interplay of p-sulfonatocalix[4]arene and crown ethers en route to molecular capsules and "Russian dolls"

Diffusion-ordered (1)H NMR spectroscopy techniques have been used to determine the binding strength of p-sulfonatocalix[4]arene (SO(3)[4]) towards a number of charged crown ether species in aqueous conditions. For several (doubly) charged (di)azacrown ethers, all were bound by SO(3)[4] either well or very well with binding constants between 5.1 x 10(2)-9.9 x 10(5) M(-1). These results correlate with, and thus explain the phenomenon of rapid capture of azacrown ethers in molecular capsules based on p-sulfonatocalix[4]arene and lanthanide metals. Similarly, the formation of "Russian doll" superanions in the solution phase is also elucidated. These superanions have been shown to selectively crystallise particular polynuclear aquated metal ions from mixtures in the aqueous phase. Neutral [18]crown-6 is not bound by p-sulfonatocalix[4]arene and displays a binding constant of 0 M(-1). When sodium [18]crown-6 is examined in a similar fashion, binding by SO(3)[4] is observed in solution with K(a) approximately 3.1 x 10(3) M(-1).     

G-quartets 40 years later: from 5'-GMP to molecular biology and supramolecular chemistry

Molecular self-assembly is central to many processes in both biology and supramolecular chemistry. The G-quartet, a hydrogen-bonded macrocycle formed by cation-templated assembly of guanosine, was first identified in 1962 as the basis for the aggregation of 5'-guanosine monophosphate. We now know that many nucleosides, oligonucleotides, and synthetic derivatives form a rich array of functional G-quartets. The G-quartet surfaces in areas ranging from structural biology and medicinal chemistry to supramolecular chemistry and nanotechnology. This Review integrates and summarizes knowledge gained from these different areas, with emphasis on G-quartet structure, function, and molecular recognition.     

Self-assembled ionophores from isoguanosine: diffusion NMR spectroscopy clarifies cation's and anion's influence on supramolecular structure

Cation-templated self-assembly of the lipophilic isoguanosine (isoG 1) with different monovalent cations (M(+)=Li(+), Na(+), K(+), NH(4) (+), and Cs(+)) was studied in solvents of different polarity by using diffusion NMR spectroscopy. Previous studies that did not use diffusion NMR techniques concluded that isoG 1 forms both pentamers (isoG 1)(5)M(+) and decamers (isoG 1)(10)M(+) in the presence of alkali-metal cations. The present diffusion NMR studies demonstrate, however, that isoG 1 does not form (isoG 1)(5)M(+) pentamers. In fact, the diffusion NMR data indicates that both doubly charged decamers of formula (isoG 1)(10)2 M(+) and singly charged decamers, (isoG 1)(10)M(+), are formed with lithium, sodium, potassium, and ammonium tetraphenylborate salts (LiB(Ph)(4), KB(Ph)(4), NaB(Ph)(4) and NH(4)B(Ph)(4)), depending on the isoG 1:salt stoichiometry of the solution. In the presence of CsB(Ph)(4), isoG 1 affords only the singly charged decamers (isoG 1)(10)Cs(+). By monitoring the diffusion coefficient of the B(Ph)(4) (-) ion in the different mixtures of solvents, we also concluded that the anion is more strongly associated to the doubly charged decamers (isoG 1)(10)2 M(+) than to the singly charged decamers (isoG 1)(10)M(+). The (isoG 1)(10)2 M(+) species can, however, exist in solution without the mediation of the anion. This last conclusion was supported by the finding that the doubly charged decamers (isoG 1)(10)2 M(+) also prevail in 1:1 CD(3)CN:CDCl(3), a solvent mixture in which the B(Ph)(4) (-) ion does not interact significantly with the self-assembled complex. These diffusion measurements, which have provided new and improved structural information about these decameric isoG 1 assemblies, demonstrate the utility of combining diffusion NMR techniques with conventional NMR methods in seeking to characterize labile, multicomponent, supramolecular systems in solution, especially those with high symmetry.     

Metal‐Directed Self‐Assembly of a Polyoxometalate‐Based Molecular Triangle: Using Powerful Analytical Tools to Probe the Chemical Structure of Complex Supramolecular Assemblies

A polyoxometalate‐based molecular triangle has been synthesized through the metal‐driven self‐assembly of covalent organic/inorganic hybrid oxo‐clusters with remote pyridyl binding sites. The new metallomacrocycle was unambiguously characterized by using a combination of ¹H NMR spectroscopy, 2D diffusion NMR spectroscopy (DOSY), electrospray ionization travelling wave ion mobility mass spectrometry (ESI‐TWIM‐MS), small‐angle X‐ray scattering (SAXS) and molecular modelling. The collision cross‐sections obtained from TWIM‐MS and the hydrodynamic radii derived from DOSY are in good agreement with the geometry‐optimized structures obtained by using theoretical calculations. Furthermore, SAXS was successfully employed and proved to be a powerful technique for characterizing such large supramolecular assemblies.     

Gold nanoparticles in organic capsules: a supramolecular assembly of gold nanoparticles and cucurbituril

Gold nanoparticles (相似文献   

NMR spectroscopy in coordination supramolecular chemistry: A unique and powerful methodology

Metal-mediated self-assembly is emerging as a very important strategy for the synthesis of supramolecular species. Still, a major challenge in coordination supramolecular chemistry continues to be the characterization of the self-assembled complexes and the investigation of their dynamic behaviour in solution. In this context, NMR spectroscopy appears as a unique and powerful methodology. This practical-oriented review describes the rich variety of NMR techniques which are applied to the investigation of different aspects of the structure and behaviour of supramolecular complexes. “Classic” 1D NMR spectra reflect characteristic chemical shifts due to metal–ligand interactions or encapsulation phenomena, as well as symmetry and chiral properties of host–guest assemblies. Mainstream ¹H, ¹³C, ¹⁹F and ³¹P spectra are eventually complemented by the use of NMR-active metal nuclides. Homo- and heteronuclear 2D correlation experiments are ubiquitous in the literature, providing through-bond and through-space connectivities. Increasingly, diffusion measurements are also gaining popularity in this field, being used to gain information about molecular size, intermolecular interactions and even association constants of supramolecular complexes. Knowledge about the thermodynamic properties and the dynamic behaviour of coordination supramolecular assemblies is essential for the development of their practical applications. The most frequently used NMR methodologies for the calculation of association constants (simple signal integration, NMR titration and diffusion measurements) and for the investigation of dynamic supramolecular equilibria (lineshape analysis, selective inversion recovery experiments and 2D EXSY spectra) are described, together with the use of variable-temperature investigations for the determination of the thermodynamic and activation parameters of self-assembly and encapsulation processes.     

N,N'-disubstituted ureas: influence of substituents on the formation of supramolecular polymers

Symmetrical N,N'-disubstituted ureas have been synthesized and characterized. Among them, the branched dialkylureas prepared are highly soluble in organic media. Moreover, the solutions obtained are very viscous in heptane, if the branched alkyl groups are not too bulky (i.e. a methyl group on the alpha carbon, or an ethyl group on the beta carbon). Due to the strong, bifurcated hydrogen bonds between the urea moieties, linear supramolecular polymers are formed. The degree of association of these supramolecular polymers has been determined by FTIR spectroscopy.     

Applications of heteronuclear NMR spectroscopy in biological and medicinal inorganic chemistry

There is a wide range of potential applications of inorganic compounds, and metal coordination complexes in particular, in medicine but progress is hampered by a lack of methods to study their speciation. The biological activity of metal complexes is determined by the metal itself, its oxidation state, the types and number of coordinated ligands and their strength of binding, the geometry of the complex, redox potential and ligand exchange rates. For organic drugs a variety of readily observed spin I = 1/2 nuclei can be used (¹H, ¹³C, ¹⁵N, ¹⁹F, ³¹P), but only a few metals fall into this category. Most are quadrupolar nuclei giving rise to broad lines with low detection sensitivity (for biological systems). However we show that, in some cases, heteronuclear NMR studies can provide new insights into the biological and medicinal chemistry of a range of elements and these data will stimulate further advances in this area.     

A supramolecular and liquid crystalline water-based alignment medium based on azobenzene-substituted 1,3,5-benzenetricarboxamides

A supramolecular, lyotropic liquid crystalline alignment medium based on an azobenzene-containing 1,3,5-benzenetricarboxamide (BTA) building block is described and investigated. As we demonstrate, this water-based system is suitable for the investigation of various water-soluble analytes and allows for a scaling of alignment strength through variation of temperature. Additionally, alignment is shown to reversibly collapse above a certain temperature, yielding an isotropic solution. This collapse allows for isotropic reference measurements, which are typically needed in addition to those in an anisotropic environment, to be performed using the same sample just by varying the temperature. The medium described thus provides easy access to anisotropic NMR observables and simplifies structure elucidation techniques based thereon.     

Tetra- and octalactam macrocycles and catenanes with exocyclic metal coordination sites: versatile building blocks for supramolecular chemistry

The synthesis of a new tetralactam macrocycle and the simultaneous formation of catenanes and larger octalactam macrocycles is reported. These species bear 2,2'-biquinoline moieties suitably positioned to bind a metal center at the outer periphery of the macrocycles. (1)H NMR chemical shifts permit the unambiguous distinction of transoid and cisoid conformations of the biquinoline moiety, thereby allowing an unequivocal identification of the catenane and octalactam structures, despite the fact that both have the same elemental composition and bear identical structural subunits. With the aid of an anion template effect, rotaxanes can be prepared from the smaller tetralactam macrocycle. These reveal significantly altered requirements in terms of the stopper size as compared to previously reported tetralactam wheels. Several copper(I)-mediated dimers and a (bpy)(2)Ru(II) complex (bpy=2,2'-bipyridine) have been synthesized from the tetralactam macrocycle and the rotaxanes. The anion binding abilities of the tetralactam macrocycle and its (bpy)(2)Ru(II) complex in DMSO have been compared by (1)H NMR titration experiments, which revealed significantly enhanced binding by the metal complex. Mass spectrometry has been used to study the potential formation of larger assemblies of copper(I) and the catenane built-up from two tetralactam macrocycles. Indeed, a 2:2 complex was identified. In contrast, the octalactam macrocycle of the same elemental composition yields only 1:1 complexes, with the Cu(I) ion connecting its two biquinoline moieties in the center of a figure-eight-shaped molecule. Molecular modeling studies support the structural assignments made.