Monomer–Dimer Control and Crystal Engineering in TASPs

We have reported a template assembled synthetic protein (cavitein Q4) as an unexpected dimer in the solid state and as a monomer–dimer equilibrium in solution. We have since reported an ability to bias a cavitein’s monomer–dimer equilibrium in solution by sequence design involving histidine metal chelation or disulfide incorporation. However, little remains known about the forces contributing to dimeric cavitein crystal nucleation and lattice stabilization. We, therefore, designed glutamine variants to probe factors involved in dimeric cavitein crystallization. It was found that a key glutamate hydrogen-bonding interaction between dimers is integral to crystal formation and stabilization. Additionally, we obtained a crystal structure of a cavitein (Q4-E3H) designed to bias the dimeric structure via histidine metal coordination. The resolved structure indicates a histidine cluster interaction that likely accounts for the biased dimeric form observed in solution.     

Novel photoswitchable receptors: synthesis and cation-induced self-assembly into dimeric complexes leading to stereospecific [2+2]-photocycloaddition of styryl dyes containing a 15-crown-5 ether unit

Styryl dyes 4a-e containing a 15-crown-5 ether unit and a quinoline residue with a sulfonatoalkyl or sulfonatobenzyl N-substituent were synthesized. The relationship between the photochemical behavior of these dyes and their aggregates derived from complexation with Mg(2+) in MeCN was studied using (1)H NMR and absorption spectroscopy. The E-isomers of 4a-e were shown to form highly stable dimeric (2:2) complexes with Mg(2+). Upon irradiation with visible light, the dimeric complexes undergo two competing photoreactions, viz., geometric E --> Z isomerization, resulting in an anion-capped 1:1 complex of the Z-isomer with Mg(2+) and stereospecific syn-head-to-tail [2+2]-cycloaddition, affording a single isomer of bis-crown-containing cyclobutane. The N-substituent in the dye has a dramatic effect on the photochemical behavior of the dimeric complex. Molecular dynamics and semiempirical quantum-chemical calculations were carried out to interpret the observed photocycloaddition in the dimer. Conformational equilibria for the dimer of (E)-4b were analyzed using (1)H NMR spectroscopy.     

Synthesis and spectroscopic and structural characterization of two novel photoactivatable Ca2+ compounds

Two novel photoactivatable Ca(2+) compounds were synthesized to achieve a fast concentration jump of calcium ions in solution; this is of paramount importance for investigating the physiological cellular response. The light-sensitive ligands 4-(2-nitrophenyl)-3,6-dioxaoctane dioic acid (H2L1) and 4-(4,5-dimethoxy-2-nitrophenyl)-3,6-dioxaoctane dioic acid (H2L2) were generated by multistep syntheses, and the corresponding calcium complexes, Ca1 and Ca2, were isolated and characterized. The solution equilibria of H2L1 and H2L2 with Ca2+ were investigated; for both ligands, the formation of a 1:2 Ca2+/ligand species is detected and the complete characterization is presented. The crystal structures of Ca1 and Ca2 were determined. In Ca1 the solid state assembly is attained by a polymeric association of [(CaL1(H2O))2(mu-OH2)] dimeric units. Each calcium ion coordinates four oxygen atoms of one ligand (two ethereal, one carboxylic, and one bridging carboxylic oxygen atom), one water molecule, one bridging water molecule, and a carboxylate group of the other ligand within the dimer. The octacoordination of the metal is completed by an interaction with the adjacent dimeric unit. The crystal structure of the complex Ca2 does not show a polymeric nature, but it is a centrosymmetric dimer. The coordination number of the metal ion is still 8:4 oxygen atoms of the ligand; 3 water molecules; 1 bridging carboxylate group. A preliminary study of the photochemical features of the complexes Ca1 and Ca2 is reported: photoexcitation by a nanosecond pulsed UV laser induces the cleavage of the ligand. This drastically reduces the affinity of the ligand toward Ca2+, which is then released in solution.     

Unprecedented π···π interaction between an aromatic ring and a pseudo-aromatic ring formed through intramolecular H-bonding in a bidentate Schiff base ligand: crystal structure and DFT calculations

A combination of a single crystal X-ray diffraction study and density functional theory calculations has been applied to a bidentate Schiff base compound to elucidate different cooperative non-covalent interactions involved in the stabilization of the keto form over the enol one in the solid state. The single crystal X-ray structure reveals a remarkable supramolecular assembly of the keto form through a cyclic hydrogen bonded dimeric motif. The most interesting feature in the supramolecular assembly is the formation of a 'dimer of dimer' motif by π···π, CH···π and N···O/O···O interactions in which the π···π interaction involving the aromatic phenyl ring and the intramolecularly hydrogen bonded pseudo-aromatic ring of the keto form lying just above or below the phenyl ring of the other dimer seems to be unprecedented. The optimized geometry of the hydrogen bonded dimeric motif of the keto form of the organic molecule has been obtained by DFT calculations and agrees very well with that found within the crystalline state. The X-ray crystallographic geometry of the 'dimer of dimer' has also been computed, which shows that in the HOMO, the π electrons are localized in the phenyl rings away from each other, while in the LUMO, there is a strong π-π interaction between the phenyl ring of one dimer with the pseudo-aromatic ring of another dimer with an energy estimated to be 7.95 kJ mol(-1). Therefore, on HOMO → LUMO excitation there is localization of π electrons in the central part of the complex moiety which plays a stabilizing role of the dimer of dimer motif in the solid state.     

H NMR investigation of the self-association of ethidium homodimer and its complexation with propidium iodide in aqueous solution

The self-association of a bis-intercalator, ethidium homodimer (EBH), and its hetero-association with phenanthridine dye, propidium iodide (PI), have been studied by 1D and 2D ¹H NMR spectroscopy using the analysis of proton chemical shifts changes in aqueous solution as a function of concentration and temperature. Experimental results have shown that dynamic equilibrium in solution includes different conformational states of EBH molecules: folded (F) and unfolded (U) forms, a dimer form (F₂) where an aromatic chromophore of one of EBH molecules is inserted (intercalated) between the linked chromophores of the other homodimer molecule and a trimer complex (F₃) with two partitially intercalated aromatic chromophores between the chromophores of the folded EBH molecule. It has been found that EBH associates with propidium iodide forming 1:1 complex, where PI is inserted between the chromophores of the folded form, and 1:2 complex resulting from intercalation of PI into F₂ EBH dimer. Thermodynamical parameters of EBH self-association and complexation between EBH and PI have been determined and conclusions about the nature of the physical forces responsible for the formation of intermolecular complexes have been made.     

From Hierarchical Helicates to Functional Supramolecular Devices

Catechol ligands with aldehyde, ketone or ester groups attached in 3-position form, in the presence of titanium(IV) triscatecholate, titanium(IV) complexes. If lithium cations are the counterions, they can bind in a successive step to the salicylate units of the complex and form a dimeric triple-lithium-bridged dinuclear helicate. In solution, the dimer is in equilibrium with the monomer and the thermodynamics of the dimerization can be easily evaluated. Thus, the hierarchically assembled titanium(IV) helicates represent a lithium-dependent molecular switch. The investigation of different derivatives of the complex allows for an estimation of the influence of side chain functionalities on the energetics of the dimerization. Thus, the hierarchically assembled helicates can be used as a kind of molecular balance to determine weak interaction energies (solvophobic effects and even dispersive effects). In addition, tethering of two ligands leads to “classical” helicates. Removal or addition of lithium cations allows for a reversible switching between a compressed and expanded state, which in the case of chiral ligands can be even performed stereospecifically.     

Structure of the cobalt complexes with the Schiff base of salicylaldehyde and lysine according to the H NMR spectroscopic data

The Co(II) complex with the Schiff base of salicylaldehyde and lysine is studied by the ¹H NMR method in dioxane and dimethyl sulfoxide (DMSO) solutions. In a dioxane solution, the complex is paramagnetic and dimeric. In the dimer, the cobalt ion coordinates two ligand molecules and each ligand is bound to two cobalt ions. In a water-containing DMSO solution, the complex is diamagnetic due to the oxidation of Co²⁺ to Co³⁺.     

Characterization of the dimeric one-electron electrolytic reduction products of 1-alkylpyridinium ions in acetonitrile

A chemical-electrochemical approach for the determination of the positions of coupling in the dimeric one-electron reduction products of 1-alkylpyridinium ions in acetonitrile is described. The procedure involves the treatment of a solution of the dimeric species with an appropriate quinone followed by electrochemical examination of the resulting solution. For 1-alkylpyridinium ions without ring substituents, the dimer is concluded to be the 4,4′ coupled isomer, based on the formation in the cases of 1-methyl-, 1-ethyl-, and 1-benzylpyridinium ions of the 1,1′-dialkyl-4,4′-bipyridinium monocation radical species on treatment of the dimeric species with 1,4-benzoquinone. The characteristics, particularly the quantitative nature, of this tetrahydrobipyridine-quinone reaction have been examined.     

Engineering an obligate domain-swapped dimer of cyanovirin-N with enhanced anti-HIV activity

The anti-HIV cyanobacterial protein cyanovirin-N can undergo domain swapping to form an intertwined dimer. The dimeric form is stable at low pH and millimolar concentrations. By deleting an amino acid from the hinge linker about which domain swapping occurs, we have constructed an obligate domain-swapped dimer of cyanovirin-N that represents a new tetravalent carbohydrate binding protein that is stable over a large range of pH values. This obligate dimer displays enhanced anti-HIV activity relative to the wild-type cyanovirin-N monomer with an observed 3.5-fold decrease in IC(50) (9nM for the dimer vs 32 nM for the monomer) for inhibition of HIV-1 envelope-mediated cell fusion and, when expressed in Escherichia coli, can be rapidly obtained in >98% purity in a single chromatographic step.     

Structure, bonding, and solvation of lithium vinylcarbenoids

[reaction: see text] Molecular modeling was used to determine the structure of lithium vinylcarbenoids in the gas phase and in THF solution. Solvent effects were modeled by microsolvation with explicit THF ligands on each of the lithium atoms. The carbenoid geometries are dependent on the heteroatom and on solvation. The calculations predict 1-chlorovinyllithium and 1-bromovinyllithium to be a mixture of monomer and dimer at 200 K and mostly monomer at higher temperatures, whereas the 1-fluoro-, 1-methoxy-, and 1-dimethylaminovinyllithium are predicted to be dimeric in solution.     

General acid catalysis in benzoic acid–Crystal Violet carbinol base reactions in toluene

Kinetics of benzoic acid–dye carbinol base reactions in an apolar aprotic solvent exhibit a complex dependence on the concentration of the acid, indicating the occurrence of general acid catalysis, the acid playing the dual role of the substrate and the catalyst. The complex kinetic behavior observed for 23 ortho‐ and meta‐substituted benzoic acids has been traced to overlapping participations of the monomer acid, hyperacidic open chain homoconjugated complex (dimeric and trimeric) acids, and nonreactive cyclic dimer and trimer acids. It has been found that although the degree of proton transfer in the transition state is 50–60% when the acid acts exclusively in the monomeric form, it gets enhanced to as high as more than 90% when the role of homoconjugated complex acids is taken into consideration. © 2012 Wiley Periodicals, Inc. Int J Chem Kinet 44: 570–576, 2012     

Monomer-Dimer Control and Crystal Engineering in TASPs

We have reported a template assembled synthetic protein (cavitein?Q4) as an unexpected dimer in the solid state and as a monomer-dimer equilibrium in solution. We have since reported an ability to bias a cavitein's monomer-dimer equilibrium in solution by sequence design involving histidine metal chelation or disulfide incorporation. However, little remains known about the forces contributing to dimeric cavitein crystal nucleation and lattice stabilization. We, therefore, designed glutamine variants to probe factors involved in dimeric cavitein crystallization. It was found that a key glutamate hydrogen-bonding interaction between dimers is integral to crystal formation and stabilization. Additionally, we obtained a crystal structure of a cavitein (Q4-E3H) designed to bias the dimeric structure via histidine metal coordination. The resolved structure indicates a histidine cluster interaction that likely accounts for the biased dimeric form observed in solution.     

Formation and stability of mononuclear and dinuclear Eu(III) complexes and their catalytic reactivity toward cleavage of an RNA analog

The complex between Eu(III) and 1,7-diaza-4,10,13-trioxacyclopentadecane-N,N'-diacetic acid (L4) was characterized by pH potentiometric titration and 1H NMR spectroscopy. The conversion of the monomer to a dimeric complex is observed as the pH is increased from 7 to 10 in a reaction that releases one mol/HO- per dimer formed. The dimeric complex undergoes a further ionization with a pKa of 10.7. Kinetic parameters are reported for the cleavage of the simple phosphodiester 2-hydroxypropyl-4-nitrophenyl phosphate catalyzed by both the monomeric and the dimeric Eu(III) complexes. These data show that the monomer and dimer stabilize their bound reaction transition states with similar free energies of 7.1 and 7.6 kcal/mol, respectively. Clearly, a bridging hydroxide is not an optimal linker to promote cooperative catalysis between Eu(III) centers in macrocycles with multiple polyaminocarboxylate pendent groups.     

Supramolecular complexes of carboxy-substituted zinc porphyrinates with triethylenediamine

α,α-and α,β-Atropoisomers of zinc 5,15-bis(2-carboxyphenyl)octaalkylporphyrinate were obtained, and their complex formation with triethylenediamine in toluene was studied. The α,α-atropoisomer is present in the solution as a supramolecular dimer and forms a 1:1 complex with the two-centered nitrogen-containing base. The complex formation of the undimerized α,β-atropoisomer with triethylenediamine can give 2:1 or 1:1 complexes, depending on the reagent ratio. The stability constants of the complexes and the concentration ranges of their formation were determined by means of spectrophotometric titration and ¹H NMR spectroscopy.     

Differential Complexing by Cyclodextrin Twin-cavity Hosts

The twin-cavity cyclodextrin (1) in which the link is a dithiotrehalosyl unit, and the flexibly-linked dimer (2) were shown to distinguish between the heterocyclic guests 3 and 4 (clofazimine drug) in spite of the guests' small structural difference. Both cyclodextrin dimer hosts form 1:1 complexes with methyl orange and with 3, as shown by double reciprocal plots of UV-absorbance change and host concentration. However with 4, both host molecules formed a 2 : 1 (host : guest) complex . Since both dimer cavities are used to create this effect, it is a new type of selectivity for macrocyclic hosts.     

Synthesis,spectroscopic studies,and preliminary antibacterial assays of a palladium(II) complex with 2-mercaptothiazoline

In this article, synthesis of a palladium(II) complex with 2-mercaptothiazoline in aqueous solution is presented. Composition of the complex was defined as 1?:?2 (metal?:?ligand). Infrared and solid-state nuclear magnetic resonance indicate ligand coordination to Pd(II) through nitrogen of thiazole ring and sulfur of thiol. ESI–QTOF–mass spectrometric analysis shows primarily the dimeric form in solution. An antibiogram assay of the complex was performed by the disc diffusion method. The compound did not show antibacterial activity against the considered bacterial cells in the tested concentrations.     

Complexation of Sc3N@C80 endohedral fullerene with cyclic Zn-bisporphyrins: solid state and solution studies

We report the synthesis of two cyclic β-pyrrole unsubstituted meso-tetraphenyl bisporphyrins in which the porphyrin units are connected by two 2,3-hexadiynyl-1,6-dioxo or two hexyl-1,6-dioxo spacers, respectively. Both cyclic porphyrin dimers exist in solution as mixtures of two conformational isomers. In the solid state, the receptor with diynyl spacers forms a 1:1 complex with the icosahedral (I(h)) isomer of the trimetallic nitride endohedral fullerene Sc(3)N@C(80). In this complex the receptor adopts a scoop-shaped conformation having a dihedral angle of 87.25° between the two porphyrin planes. The hexyl spaced analogue, however, adopts a similar conformation upon encapsulation of one molecule of Sc(3)N@C(80) in a self-assembled dimeric capsule. The capsular complexes pack in columns and render the fullerene units completely isolated. In toluene solution, (1)H NMR experiments indicate that the endohedral fullerene Sc(3)N@C(80) is exclusively bound by the expanded isomer of both dimers. UV-vis and fluorescence titration experiments confirmed the existence of strong π-π interactions between the fullerene Sc(3)N@C(80) and the flexible bisporphyrin dimer with hexyl spacers. At micromolar concentration, the flexible receptor forms only a 1:1 complex with the endohedral fullerene with stability constant value of K(a) = 2.6 ± 0.3 × 10(5) M(-1).     

On the Electrochemistry and Spectroelectrochemistry of Small Model Star‐Shaped Compounds: 1,3,5‐Triaryl‐1‐Methoxybenzenes and 2,4,6‐Triaryl‐1,3,5‐Trimethoxybenzenes

Model structures of 1,3,5‐triarylbenzenes with a substituted benzene core linked to thienyl or 3,4‐ethylenedioxythienyl (EDOT) terminal groups are studied by electrochemical and in situ ESR/UV/Vis/NIR spectroelectrochemical techniques. Oxidative polymerization of the monomers results in C? C coupling of the thiophene moieties in the 5‐position, forming dimeric structures with bithiophene linkers as the first step. Both the doubly charged protonated dimer and the new dimer formed after proton release are studied in detail for 2,4,6‐tris[2‐(3,4‐ethylenedioxythienyl)]‐1‐methoxybenzene. Quite high stability of the doubly charged σ dimer formed on oxidation with unusual redox behavior at the electrode is observed. Density functional calculations of the molecular structure as well as spectroscopic and electronic properties of charged states in 1,3,5‐triarylbenzene derivatives in the monomeric, dimeric, and oligomeric form are presented. The complex spectroelectrochemical response of a thin solid film formed on the electrode surface upon potentiodynamic polymerization indicates the existence of different charge states of oligomeric structures within the solid matrix.     

Preparation and properties of inclusion compound of cyclopentadienylmanganese tricarbonyl complex with a ß-cyclodextrin dimer

The host-guest inclusion compound of cyclopentadienylmanganese tricarbonyl (guest) with ß-cyclodextrin dimer (host) bridged with two 1,2-diaminoethane has been prepared as the first example of cyclodextrin dimer inclusion compounds with organotransition metal complexes and characterized by elemental analysis and IR spectra as well as thermogravimetric analysis. The manganese complex included in the dimer is thermally more stable than the free complex. ¹H NMR spectroscopy has established that the cyclopentadienylmanganese complex and the dimer form an inclusion compound in aqueous solution with a stability constant (β₂, 195 mol⁻²l²) at 22°C. The spectroscopic studies and the results of elemental analysis revealed that stoichiometry (1:2, host: guest) of the inclusion compound in water is identical to its stoichiometry in solid state.     

Monomer–Dimer Equilibrium for the 5′–5′ Stacking of Propeller‐Type Parallel‐Stranded G‐Quadruplexes: NMR Structural Study

Guanine‐rich sequence motifs, which contain tracts of three consecutive guanines connected by single non‐guanine nucleotides, are abundant in the human genome and can form a robust G‐quadruplex structure with high stability. Herein, by using NMR spectroscopy, we investigate the equilibrium between monomeric and 5′–5′ stacked dimeric propeller‐type G‐quadruplexes that are formed by DNA sequences containing GGGT motifs. We show that the monomer–dimer equilibrium depends on a number of parameters, including the DNA concentration, DNA flanking sequences, the concentration and type of cations, and the temperature. We report on the high‐definition structure of a simple monomeric G‐quadruplex containing three single‐residue loops, which could serve as a reference for propeller‐type G‐quadruplex structures in solution.