Complexation-induced Shifts Research Articles

Shape-, Size-, and Functional Group-Selective Binding of Small Organic Guests in a Paramagnetic Coordination Cage

The host-guest chemistry of the octanuclear cubic coordination cage [Co(8)L(12)](16+) (where L is a bridging ligand containing two chelating pyrazolyl-pyridine units connected to a central naphthalene-1,5-diyl spacer via methylene "hinges") has been investigated in detail by (1)H NMR spectroscopy. The cage encloses a cavity of volume of ca. 400 Å(3), which is accessible through 4 Å diameter portals in the centers of the cube faces. The paramagnetism of the cage eliminates overlap of NMR signals by dispersing them over a range of ca. 200 ppm, making changes of specific signals easy to observe, and also results in large complexation-induced shifts of bound guests. The cage, in CD(3)CN solution, acts as a remarkably size- and shape-selective host for small organic guests such as coumarin (K = 78 M(-1)) and other bicyclic molecules of comparable size and shape such as isoquinoline-N-oxide (K = 2100 M(-1)). Binding arises from two independent recognition elements, which have been separately quantified. These are (i) a polar component arising from interaction of the H-bond accepting O atom of the guest with a convergent group of CH protons inside the cavity that lie close to a fac tris-chelate metal center and are therefore in a region of high electrostatic potential; and (ii) an additional component arising from the second aromatic ring (aromatic/van der Waals interactions with the interior surface of the cage and/or solvophobic interactions). The strength of the first component varies linearly with the H-bond-accepting ability of the guest; the second component is fixed at approximately 10 kJ mol(-1). We have also used (1)H-(1)H exchange spectroscopy (EXSY) experiments to analyze semiquantitatively two distinct dynamic processes, viz. movement of the guest into and out of the cavity and tumbling of the guest inside the host cavity. Depending on the size of the guest and the position of substituents, the rates of these processes can vary substantially, and the rates of processes that afford observable cross-peaks in EXSY spectra (e.g., between free and bound guest in some cases; between different conformers of a specific host·guest complex in others) can be narrowed down to a specific time window. Overall, the paramagnetism of the host cage has allowed an exceptionally detailed analysis of the kinetics and thermodynamics of its host-guest behavior.

Complexations of the hydrophilic and hydrophobic moieties of benzethonium chloride by cucurbit[7]uril in aqueous solution

The sequential complexations of the hydrophilic and hydrophobic end groups of benzethonium chloride by cucurbit[7]uril (CB[7]) in aqueous solution have been investigated using 1H NMR spectroscopy and electrospray ionization mass spectrometry. The initial binding is to the benzyldimethylammonium group, with a stability constant of (8.7 ± 3.1) × 107 (mol/L)–1. This binding constant and the complexation-induced upfield shifts of the benzyl guest protons are similar to those values observed with other cationic guests containing benzyl moieties. This equilibrium is followed by the binding of a second equivalent of the host to the hydrophobic 2-(2,4,4-trimethylpentyl) group, with a stability constant of (4.0 ± 1.9) × 103 (mol/L)–1. The relatively strong binding of this uncharged hydrophobic end of the guest molecule is consistent with the inclusion of eight heavy (nonhydrogen) atoms within the inner cavity of CB[7], with its low polarizability. The packing coefficient for the 2-(2,4,4-trimethylpentyl) group with the inner cavity is calculated to be 61%, close to Rebek’s ideal value of 55%.

A study of TDDFT performance in modeling of spectral changes induced by interactions of ketocyanine dyes with inorganic ions

DFT/TDDFT calculations were conducted for series of ketocyanine dye complexes with inorganic cations in acetonitrile and acetone. Four functionals were investigated: B3LYP, CAM-B3LYP, LC-PBE and wB97XD. Franck–Condon vibrational analysis was performed to simulate the shape of absorption and emission spectra. Results of computations were compared with available experimental data. The best reproduction of the positions of maxima in absorption and emission spectra was obtained for B3LYP. wB97XD and CAM-B3LYP performed better in the prediction of complexation-induced spectral shifts.

Embedding vs Supermolecular Strategies in Evaluating the Hydrogen-Bonding-Induced Shifts of Excitation Energies

Shifts in the excitation energy of the organic chromophore, cis-7-hydroxyquinoline (cis-7HQ), corresponding to the π→π* transition in cis-7HQ and induced by the complexation with a variety of small hydrogen-bonded molecules, obtained with the frozen-density embedding theory (FDET), are compared with the results of the supermolecular equation-of-motion coupled-cluster (EOMCC) calculations with singles, doubles, and non-iterative triples, which provide the reference theoretical data, the supermolecular time-dependent density functional theory (TDDFT) calculations, and experiment. Unlike in the supermolecular EOMCC and TDDFT cases, where each complexation-induced spectral shift is evaluated by performing two separate calculations, one for the complex and another one for the isolated chromophore, the FDET shifts are evaluated as the differences of the excitation energies determined for the same many-electron system, representing the chromophore fragment with two different effective potentials. By considering eight complexes of cis-7HQ with up to three small hydrogen-bonded molecules, it is shown that the spectral shifts resulting from the FDET calculations employing non-relaxed environment densities and their EOMCC reference counterparts are in excellent agreement with one another, whereas the analogous shifts obtained with the supermolecular TDDFT method do not agree with the EOMCC reference data. The average absolute deviation between the complexation-induced shifts, which can be as large, in absolute value, as about 2000 cm-1, obtained using the non-relaxed FDET and supermolecular EOMCC approaches that represent two entirely different computational strategies, is only about 100 cm-1, i.e., on the same order as the accuracy of the EOMCC calculations. This should be contrasted with the supermolecular TDDFT calculations, which produce the excitation energy shifts that differ from those resulting from the reference EOMCC calculations by about 700 cm-1 on average. Among the discussed issues are the choice of the electronic density defining the environment with which the chromophore interacts, which is one of the key components of FDET considerations, the basis set dependence of the FDET, supermolecular TDDFT, and EOMCC results, the usefulness of the monomer vs supermolecular basis expansions in FDET considerations, and the role of approximations that are used to define the exchange-correlation potentials in FDET and supermolecular TDDFT calculations.

The World of Cucurbiturils — From Peculiarity to Commodity

The World of Cucurbiturils — From Peculiarity to Commodity

Methylated β-Cyclodextrins: Influence of Degree and Pattern of Substitution on the Thermodynamics of Complexation with Tauro- and Glyco-Conjugated Bile Salts

The complexation of 6 bile salts with various methylated β-cyclodextrins was studied to elucidate how the degree and pattern of substitution affects the binding. The structures of the CDs were determined by mass spectrometry and NMR techniques, and the structures of the inclusion complexes were characterized from the complexation-induced shifts of (13)C nuclei as well as by 2D ROESY NMR. Thermodynamic data were generated using isothermal titration calorimetry. The structure-properties analysis showed that methylation at O3 hinders complexation by partially blocking the cavity entrance, while methyl groups at O2 promote complexation by extending the hydrophobic cavity. Like in the case of 2-hydroxypropylated cyclodextrins, the methyl substituents cause an increased release of ordered water from the hydration shell of the bile salts, resulting in a strong increase in both the enthalpy and the entropy of complexation with increased number of methyl substituents. Due to enthalpy-entropy compensation the effect on the stability constant is relatively limited. However, when all hydroxyl groups are methylated, the rigid structure of the free cyclodextrin is lost and the complexes are severely destabilized due to very unfavorable entropies.

Structural characterization of the Brooker’s merocyanine/β-cyclodextrin complex using NMR spectroscopy and molecular modeling

Brooker’s merocyanine (4-[(1-methyl-4(1H)-pyridinylidene)ethylidene]-2,5-cyclohexadien-1-one) is a dye molecule that has a unique photochemical/protolytic isomerization cycle. The cis to trans isomerization of the neutral molecule occurs only in one direction with the addition of photochemical energy. When the dye molecule is complexed with β-cyclodextrin, however, the isomerization occurs spontaneously without further energy required. To understand the difference between the native dye molecule and the complex, the molecular structures of the cis and trans isomers of Brooker’s merocyanine in β-cyclodextrin were optimized using the semi-empirical PM3 method as well as the hybrid ONIOM method which models the cyclodextrin at the PM3 level and the dye molecule using B3LYP/6-31g(d). The most stable complexes were similar in binding energy, although the molecular structures were quite different. The ONIOM optimized structures resulted in an increase in the planarity of the conjugated dye molecule when compared to the PM3 model. The trans isomer in the β-cyclodextrin cavity was also characterized experimentally using 1H-NMR complexation-induced shifts, and the results were found to be in good agreement with the proposed structure from the molecular modeling. Finally, the calculated thermodynamic properties of the trans isomer complex were compared to experimental results, and it became clear that water within the cavity must be included in the analysis to obtain accurate theoretical values.

Dithiocarbamate-Coated SERS Substrates: Sensitivity Gain by Partial Surface Passivation

The surface-enhanced Raman scattering (SERS) activity of nanoporous gold (NPG) can be boosted by controlled surface passivation. The SERS activities of unfunctionalized NPG were first optimized by etching substrates with NaI/I(2) (triiodide) and using 2-mercaptopyridine (2-MP) as the probing analyte. Gains in analyte sensitivity were then achieved by passivating the superficial regions of the NPG substrates with dimethyldithiocarbamate (Me(2)DTC) while leaving the more recessed "hot spots" available for SERS detection. Partial surface passivation with DTCs increased the substrate sensitivity to chemisorptive analytes such as 2-MP by an order of magnitude, whereas surface saturation lowered the sensitivity by an order of magnitude. The partially passivated NPG films can also be functionalized with supramolecular receptors for chemoselective SERS. Installation of a DTC-anchored terpyridine enabled the detection of divalent metal ions at trace levels, as determined by the complexation-induced shift of a characteristic Raman peak of the metal ion receptor.

Enantioselective host–guest complexation of Ru(II) trisdiimine complexes using neutral and anionic derivatized cyclodextrins

Enantioselective host–guest complexation between five racemic Ru(II) trisdiimine complexes and eight derivatized cyclodextrins (CDs) has been examined by NMR techniques. The appearance of non-equivalent complexation-induced shifts of between the Δ and Λ-enantionomers of the Ru(II) trisdiimine complexes and derivatized CDs is readily observed by NMR. In particular, sulfobutyl ether-β-cyclodextrin sodium salt (SBE-β-CD), R-naphtylethyl carbamate β-cyclodextrin (RN-β-CD), and S-naphtylethyl carbamate β-cyclodextrin (SN-β-CD) showed good enantiodiscrimination for all five Ru complexes examined, which indicates that aromatic and anionic derivatizing groups are beneficial for chiral recognition. The complexation stoichiometry between SBE-β-CD and [Ru(phen) 3] 2+ was found to be 1:1 and binding constants reveal that Λ-[Ru(phen) 3] 2+ binds more strongly to SBE-β-CD than the Δ-enantiomer. Correlations between this NMR method and separative techniques based on CDs as chiral discriminating agents (i.e., selectors) are discussed in detail.

Design of a Fluorescent Dye for Indicator Displacement from Cucurbiturils: A Macrocycle-Responsive Fluorescent Switch Operating through a pKa Shift

The derivatization of 3-amino-9-ethylcarbazole with a diamino-alkyl anchor affords a fluorescent dye suitable for indicator displacement from cucurbituril macrocycles. The novel compound 1 shows, due to a complexation-induced pKa shift, a large and predictable dual fluorescence response (100-fold increase at 375 nm and 9-fold decrease at 458 nm) upon supramolecular encapsulation and a strong affinity for cation-receptor macrocycles, in particular cucurbit[6]uril (CB6). A direct application is presented by monitoring the enzymatic activity of lysine decarboxylase.

Novel calixarene–Schiff bases that bind silver(I) ion

Two novel calix[4]arene–Schiff base receptors have been synthesized. One of the new compounds has two pendant aldimines, while the second has been prepared by two-point attachment of a calixarene–dialdehyde onto a calixarene–diamine to form a “calix-tube”. Preliminary binding studies with AgClO 4 show large complexation-induced shifts in 1H NMR positions.

Anisotropic effect of the nitrate anion—manifestation of diamagnetic proton chemical shifts in the 1H NMR spectra of NO 3− coordinated complexes

The anisotropic effect of the planar nitrate anion NO 3 − has been ab initio calculated employing the Nucleus-Independent Chemical Shift (NICS) concept of von Ragué Schleyer and visualized as Iso-Chemical-Shielding Surfaces (ICSSs) of various (de)shieldings. Complexation-induced shifts in the 1H NMR spectra of nitrate/metal complexes or nitrate/receptor supramolecules can be separated now into anisotropic influences of the suitably coordinated nitrate anions and effects originating from differential sources.

Multi-Component Synthesis of Tetracavitand Nanocapsules

The syntheses of three hexadecaimino nanocapsules 4b–d via the trifluoroacetic acid-catalysed condensation of four equivalents of a tetraformylcavitand 2 with eight equivalents of 1,4-phenylenediamine 3b, benzidine 3c or 4,4′-ethylenedianiline 3d, respectively, are reported. These nanocapsules are shaped like a tetragonal tetrahedron and have solvodynamic diameters of 2.5–3 nm, which were estimated from their diffusion constants. The smallest of these tetragonal tetrahedra 4b, which has a cavity volume of 1250 Å3, forms 1:1 and 2:1 complexes with R4N+Br− salts (R = n-pentyl, n-hexyl, n-heptyl) in organic solvents. Complexation-induced shifts and the slow exchange rates between the free and complexed guests are consistent with the guest being fully encapsulated inside the nanocapsule.

NMR crystallography of p-tert-butylcalix[4]arene host–guest complexes using 1H complexation-induced chemical shifts

(1)H magic-angle spinning (MAS) NMR spectra of p-tert-butylcalix[4]arene inclusion compounds with toluene and pyridine show large complexation-induced shifts of the guest proton resonances arising from additional magnetic shielding caused by the aromatic rings of the cavities of the host calixarene lattice. In combination with ab initio calculations, these observations can be employed for NMR crystallography of host-guest complexes, providing important spatial information about the location of the guest molecules in the host cavities.

Experimental and Theoretical Investigations into the Paratropic Ring Current of a Porphyrin Sheet

Anomalous induced magnetic effects were observed in a directly fused square-planar porphyrin sheet 1, in that the protons above the center of the tetraporphyrin core were characteristically shifted downfield in the 1H NMR spectrum. These observations suggest a rare paratropic ring-current effect around the planar cyclooctatetraene (COT) core of 1. To examine the spatial distribution of the induced magnetic effect, face-to-face dimeric complexes of porphyrin sheet 1 with bipyridyl-type guest molecules (G1-G3) were prepared, which provided complexation-induced shifts (CISs) of the guest molecules as a neat experimental guide to the distance dependence of the induced magnetic effects in 1. Nucleus-independent chemical shift (NICS) values of 1 were calculated by varying the distance of the probe from the plane of 1. Whereas a simple bell-type profile was estimated for the complex (1)2-(G1)4, the distance profiles of the CIS became increasingly flat for (1)2-(G2)4 and (1)2-(G3)4. Finally, we investigated the paratropic ring-current effect just above the COT core of the complex 1-(G4)2, which agrees well with the theoretically estimated distance-dependent induced magnetic effect. Consequently, both experimental and theoretical studies on the complexes of porphyrin sheets with guest molecules revealed for the first time a unique distance dependence of the paratropic ring current.

Selective Sensing of Citrate by a Supramolecular 1,8-Naphthalimide/Calix[4]arene Assembly via Complexation-Modulated pKaShifts in a Ternary Complex

A water-soluble supramolecular sensing assembly, composed of an imidazolium-substituted calix[4]arene and a fluorescent aminodiacetate derivative of 1,8-naphthalimide, was studied. Addition of citrate led to a large fluorescence enhancement, while tartrate, acetate, as well as selected inorganic anions gave smaller effects. The sensing principle and selectivity for citrate rely on the formation of a ternary fluorophore-host-anion complex and complexation-induced pKa shifts of an amino group attached to the fluorophore. The complexation of citrate induces a protonation of the amino group, which switches off intramolecular photoinduced electron transfer as the fluorescence quenching pathway, leading to an enhancement of the optical output signal. The intricate sensor principle was corroborated by pH titrations, binding constants, and structural information as obtained by 1H NMR spectroscopy.

Manifestation of diamagnetic chemical shifts of proton NMR signals by an anisotropic shielding effect of nitrate anions

A remarkable upfield shift of the py α protons of complexed 2,2′-bipyridine in [ cis-Pd(bpy)(NO 3) 2] is observed which is considered to originate from the anisotropic influence of suitably positioned coordinated nitrate anions around the Pd(II) centre of the molecule. A typical complexation-induced downfield shift is observed for the NH 2 protons in [ cis-Pd(en)(NO 3) 2] where ‘en’ stands for ethylenediamine.

Host–Guest Complexation Behavior of Resorcinarenes with Tetraalkylammonium Ions and N-Methylpyridinium Ions in Methanol: The Effect of Bulky Hydrophobic Substituents at the Extra-Annular Positions

The host–guest interaction of C-methylresorcin[4]arene and its derivative having four tert-butylsulfanylmethyl groups at the extra-annular positions was studied by 1 H NMR spectroscopy in CD3OD. Based on the association constants (Ka) and the complexation-induced NMR shifts (CIS), it was concluded that the bulky substituents create a deep cavity with a narrow entrance and improve the size and shape selectivity.

Cucurbit[7]uril host-guest complexes with cationic bis(4,5-dihydro-1H-imidazol-2-yl) guests in aqueous solution

The host–guest interactions between cucurbit[7]uril and a series of novel cationic bis(4,5-dihydro-1H-imidazol-2-yl)arene and 1-(4,5-dihydro-1H-imidazol-2-yl)- and 1,3-bis(4,5-dihydro-1H-imidazol-2-yl)-adamantane guests have been investigated in aqueous solution using UV–vis and NMR spectroscopy, and electrospray mass spectrometry. With the exception of the 1,3-bis(4,5-dihydro-1H-imidazol-2-yl)adamantane (which binds externally to the CB[7]), these guests form very stable inclusion complexes with slow exchange on the 1H NMR timescale. The direction and magnitude of the complexation-induced shifts (CIS) in the proton resonances of the guests are indicative of the residence of the hydrophobic core of the guest within the CB[7] cavity and the charged 4,5-dihydro-1H-imidazol-2-yl units outside the cavity adjacent to the carbonyl-lined portals of the host. The CIS values and the inclusion stability constants have been correlated with the nature of the guest core and with the distance between the charges on the terminal 4,5-dihydro-1H-imidazol-2-yl rings.Key words: cucurbit[7]uril, host–guest complex, dihydroimidazolyl, inclusion stability constants.

Host−Guest Complexes between an Aromatic Molecular Tweezer and Symmetric and Unsymmetric Dendrimers with a 4,4‘-Bipyridinium Core

We have investigated the spectroscopic and electrochemical behavior of symmetric and unsymmetric first-, second-, and third-generation dendrimers comprising an electron-acceptor 4,4'-bipyridinium core (viologen type) and electron-donor 1,3-dimethyleneoxybenzene (Fréchet-type) dendrons. The quite strong fluorescence of the symmetrically and unsymmetrically disubstituted 1,3-dimethyleneoxybenzene units of the dendrons is completely quenched as a result of donor-acceptor interactions that are also evidenced by a low-energy tail in the absorption spectrum. In dichloromethane solution, the 4,4'-bipyridinium cores of the investigated dendrimers are hosted by a molecular tweezer comprising a naphthalene and four benzene components bridged by four methylene units. Host-guest formation causes the quenching of the tweezer fluorescence. The association constants, as measured from fluorescence and (1)H NMR titration plots, (i) are of the order of 10(4) M(-1), (ii) decrease on increasing dendrimer generation, and (iii) are slightly larger for the unsymmetric than for the symmetric dendrimer of the same generation. The analysis of the complexation-induced shifts of the temperature-dependent (1)H NMR signals of the host and guest protons confirms that the bipyridinium core is positioned inside the tweezer cavity and allows the conclusions that (i) shuttling of the tweezer from one to the other pyridinium ring is fast (DeltaG < 10 kcal/mol), (ii) in the case of the unsymmetric dendrimers, the less substituted pyridinium ring is preferentially complexed in apolar solvents, and (iii) complexation of the 4,4'-bipyridinium core proceeds by clipping for the symmetric dendrimers and by threading in the case of unsymmetric ones. Host-guest formation causes a displacement of the first reduction wave of the 4,4'-bipyridinium unit toward more negative potential values, whereas the second reduction wave is unaffected. These results show that the host-guest complexes between the tweezer and the dendrimers are stabilized by electron donor-acceptor interactions and can be reversibly assembled/disassembled by electrochemical stimulation.