Enantioseparations of polyhalogenated 4,4’-bipyridines on polysaccharide-based chiral stationary phases and molecular dynamics simulations of selector–selectand interactions

2’-(4-Pyridyl)- and 2’-(4-hydroxyphenyl)-TCIBPs (TCIBP = 3,3’,5,5’-tetrachloro-2-iodo-4,4’-bipyridyl) are chiral compounds that showed interesting inhibition activity against transthyretin fibrillation in vitro. We became interested in their enantioseparation since we noticed that the M-stereoisomer is more effective than the P-enantiomer. Based thereon, we recently reported the enantioseparation of 2’-substituted TCIBP derivatives with amylose-based chiral columns. Following this study, herein we describe the comparative enantioseparation of both 2’-(4-pyridyl)- and 2’-(4-hydroxyphenyl)-TCIBPs on four cellulose phenylcarbamate-based chiral columns aiming to explore the effect of the polymer backbone, as well as the nature and position of substituents on the side groups on the enantioseparability of these compounds. In the frame of this project, the impact of subtle variations of analyte and polysaccharide structures, and mobile phase (MP) polarity on retention and selectivity was evaluated. The effect of temperature on retention and selectivity was also considered, and overall thermodynamic parameters associated with the analyte adsorption onto the CSP surface were derived from van ’t Hoff plots. Interesting cases of enantiomer elution order (EEO) reversal were observed. In particular, the EEO was shown to be dependent on polysaccharide backbone, the elution sequence of the two analytes being P-M and M-P on cellulose and amylose tris(3,5-dimethylphenylcarbamate), respectively. In this regard, a theoretical investigation based on molecular dynamics (MD) simulations was performed by using amylose and cellulose tris(3,5-dimethylphenylcarbamate) nonamers as virtual models of the polysaccharide-based selectors. This exploration at the molecular level shed light on the origin of the enantiodiscrimination processes.     

Reversible Immobilization of Peptides: Surface Modification and In Situ Detection by Attenuated Total Reflection FTIR Spectroscopy

A generic method is described for the reversible immobilization of polyhistidine‐bearing polypeptides and proteins on attenuated total reflecting (ATR) sensor surfaces for the detection of biomolecular interactions by FTIR spectroscopy. Nitrilotriacetic acid (NTA) groups are covalently attached to self‐assembled monolayers of either thioalkanes on gold films or mercaptosilanes on silicon dioxide films deposited on germanium internal reflection elements. Complex formation between Ni²⁺ ions and NTA groups activates the ATR sensor surface for the selective binding of polyhistidine sequences. This approach not only allows a stable and reversible immobilization of histidine‐tagged peptides (His–peptides) but also simultaneously allows the direct in situ quantification of surface‐adsorbed molecules from their specific FTIR spectral bands. The surface concentrations of both NTA and His–peptide on silanized surfaces were determined to be 1.1 and 0.4 molecules nm^?2, respectively, which means that the surface is densely covered. A comparison of experimental FTIR spectra with simulated spectra reveals a surface‐enhancement effect of one order of magnitude for the gold surfaces. With the presented sensor surfaces, new ways are opened up to investigate, in situ and with high sensitivity and reproducibility, protein–ligand, protein–protein, protein–DNA interactions, and DNA hybridization by ATR–FTIR spectroscopy.     

Self-assembled metallocycles with two interactive binding domains

Five metallocycles 1 a-e have been self-assembled from S-shaped bispyridyl ligands 2 a-e and a palladium complex, [Pd(dppp)(OTf)(2)] (dppp=1,3-bis(diphenylphosphanyl)propane), and have been characterized by elemental analysis and various spectroscopic methods including (1)H NMR spectroscopy and electrospray ionization (ESI) mass spectrometry. These metallocycles all are monocyclic compounds, but can fold to generate two binding domains bearing hydrogen-bonding sites based on pyridine-2,6-dicarboxamide units. The binding properties of the metallocycles with N,N,N',N'-tetramethylterephthalamide (G) have been probed by means of ESI mass spectrometry and (1)H NMR spectroscopy. The results both in the gas phase and in solution are consistent with the fact that the metallocycles accommodate two molecules of the guest G. Thus, the ESI mass spectra clearly show fragments corresponding to the 1:2 complexes in all cases. (1)H NMR studies on 1 a and G support the formation of a 1:2 complex in solution; the titration curves are nicely fitted to a 1:2 binding isotherm, but not to a 1:1 binding isotherm. In addition, a Job plot also suggests a 1:2 binding mode between 1 a and G, showing maximum complexation at approximately 0.33 mol fraction of the metallocycle 1 a in CDCl(3). The binding constants K(1) and K(2) are calculated to be 1600 and 1400 M(-1) (+/-10 %), respectively, at 25 degrees C in CDCl(3), indicative of positively cooperative binding. This positive cooperativity was confirmed by the Hill equation, affording a Hill coefficient of n = 1.6. Owing to insufficient solubility in CDCl(3), for comparison purposes the binding properties of the metallocycles 1 b-e were investigated in a more polar medium, 3 % CD(3)CN/CDCl(3). (1)H NMR titrations revealed that the metallocycles all bind two molecules of the guest G with Hill coefficients ranging from 1.4 to 1.8. This positive cooperativity may be attributed to a structural reorganization of the second binding cavity when the first guest binds to either one of the subcavities present in the metallocycles.     

Syntheses,Characterization and Crystal Structures of Three Structurally Similar Dinuclear Schiff Base Cadmium(II) Complexes with Bridging Azide or Thiocyanate Ligands

Three novel Schiff base cadmium(II) complexes, derived from the end‐on (μ‐1,1‐N₃) azide or end‐to‐end (μ‐1,3‐NCS) thio cyanate bridges and similar tridentate Schiff base ligands, have been synthesized under similar synthetic procedures and their crystal structures determined by X‐ray diffraction methods. They are the dinuclear double end‐on azide‐bridged [Cd₂(L1)₂(N₃)₂(μ‐1,1‐N₃)₂] ( 1 ), the dinuclear double end‐on azide‐bridged [Cd₂(L2)₂(N₃)₂(μ‐1,1‐N₃)₂] ( 2 ), and the dinuclear double end‐to‐end thiocyanate‐bridged [Cd₂(L3)₂(NCS)₂(μ_1,3‐NCS)₂] ( 3 ), where L1, L2 and L3 are three similar tridentate Schiff bases obtained by condensation of 2‐pyridylaldehyde with N,N‐diethylethane‐1,2‐diamine, of 2‐pyridylaldehyde with N‐isopropylethane‐1,2‐diamine, and of 2‐pyridylaldehyde with N,N‐dimethylpropane‐1,3‐diamine, respectively. Each cadmium(II) centre in the complexes is in a distorted octahedral coordination. There is a crystallographic inversion centre in each of the complexes. The similar small ligands used as the secondary ligands in the preparation of the cadmium(II) complexes with similar Schiff bases can result in similar structures.     

Electrostatic interaction between ion-penetrable membranes in a salt-free medium

A set of coupled equations is given which determines the distributions of the electric potential and counterions in a system of two interacting identical ion-penetrable membranes of thickness d at separation h immersed in a salt-free medium containing only counterions. The solution to these coupled equations also gives the electrostatic repulsive force between the membranes. It is shown that the interaction force remains finite at h-->0, unlike the case of the interaction between two planar charged surfaces (d-->0), and that the interaction force becomes independent of the membrane fixed charge and membrane thickness d at very large h. Finally, an approximate single transcendental equation giving the solution to the coupled equations is derived.     

Metal-complex assemblies constructed from the flexible hinge-like ligand H2bhnq: structural versatility and dynamic behavior in the solid state

Novel metal-complex assemblies constructed from the flexible hinge-like ligand H(2)bhnq (H(2)bhnq=2,2'-bi(3-hydroxy-1,4-naphthoquinone)) have been synthesized. The X-ray crystal structures of these compounds reveal that four types of architectures are accessible by variation of the metal ions. In copper(II) compounds 1-3, the chelating bhnq(2-) ions bridge copper(II) centers to form one-dimensional zigzag chains. The chains of 1-3 are arranged by hydrogen-bonding interactions and stacking interactions to produce porous structures. Cobalt(II) and zinc(II) compounds 4 and 5 form one-dimensional helical chains. In 4 and 5, the crystal packing induces spontaneous resolution of the helical chains with chiral cavities formed perpendicular to the helices. Nickel(II) compounds 6 and 7 form cyclic tetramers. The fourth architecture, a dimer (compound 8), is obtained by the reaction of zinc(II) and bhnq(2-) in MeOH. In these compounds, changes of the dihedral angles and the metal-coordination mode of the bhnq(2-) ion induce the structural versatility. The assemblies of the zigzag chains of the copper(II) compounds exhibit reversible vapochromic behavior. UV/Vis, powder X-ray diffraction, EPR, and adsorption isotherm measurements indicate that this vapochromic behavior is based on the hinge-like flexibility of the bhnq(2-) ion.     

Triple hydrogen bonds direct crystal engineering of metal-assembled complexes: the effect of a novel organic-inorganic module on supramolecular structure

Novel triply hydrogen bonded suprastructures based on [M(tdpd)2(L)2]2- (H2tdpd=1,4,5,6-tetrahydro-5,6-dioxo-2,3-pyrazinedicarbonitrile, L=solvent) and melamine-analogous cations have been synthesized and characterized. The use of anions containing two AAA sets from [M(tdpd)2(L)2]2- together with cations containing one DDD set (A=hydrogen-bond acceptor, D=hydrogen-bond donor) leads to the formation of complementary triply hydrogen bonded modules in the solid state. In all cases, the building module is further extended via additional hydrogen-bonding interactions to produce a tape, and tapes are assembled into sheets. These results show that a hydrogen-bonded module consisting of different kinds of building blocks, one of which is a metal complex that includes hydrogen-bond acceptor sites and the other is a hydrogen-bond donor molecule, will be attractive for constructing metal-containing supramolecular systems by the self-assembly technique.     

Controllable donor-acceptor neutral [2]rotaxanes

In pursuit of a neutral bistable [2]rotaxane made up of two tetraarylmethane stoppers--both carrying one isopropyl and two tert-butyl groups located at the para positions on each of three of the four aryl rings--known to permit the slippage of the pi-electron-donating 1,5-dinaphtho[38]crown-10 (1/5DNP38C10) at the thermodynamic instigation of pi-electron-accepting recognition sites, in this case, pyromellitic diimide (PmI) and 1,4,5,8-naphthalenetetracarboxylate diimide (NpI) units separated from each other along the rod section of the rotaxane's dumbbell component, and from the para positions of the fourth aryl group of the two stoppers by pentamethylene chains, a modular approach was employed in the synthesis of the dumbbell-shaped compound NpPmD, as well as of its two degenerate counterparts, one (PmPmD) which contains two PmI units and the other (NpNpD) which contains two NpI units. The bistable [2]rotaxane NpPmR, as well as its two degenerate analogues PmPmR and NpNpR, were obtained from the corresponding dumbbell-shaped compounds NpPmD, PmPmD, and NpNpD and 1/5DNP38C10 by slippage. Dynamic 1H NMR spectroscopy in CD2Cl2 revealed that shuttling of the 1/5DNP38C10 ring occurs in NpNpR and PmPmR, with activation barriers of 277 K of 14.0 and 10.9 kcal mol(-1), respectively, reflecting a much more pronounced donor-acceptor stabilizing interaction involving the NpI units over the PmI ones. The photophysical and electrochemical properties of the three neutral [2]rotaxanes and their dumbbell-shaped precursors have also been investigated in CH2Cl2. Interactions between 1/5DNP38C10 and PmI and NpI units located within the rod section of the dumbbell components of the [2]rotaxane give rise to the appearance of charge-transfer bands, the energies of which correlate with the electron-accepting properties of the two diimide moieties. Comparison between the positions of the visible absorption bands in the three [2]rotaxanes shows that, in NpPmR, the major translational isomer is the one in which 1/5DNP38C10 encircles the NpI unit. Correlations of the reduction potentials for all the compounds studied confirm that, in this non-degenerate [2]rotaxane, one of the translational isomers predominates. Furthermore, after deactivation of the NpI unit by one-electron reduction, the 1/5DNP38C10 macrocycle moves to the PmI unit. Li+ ions have been found to strengthen the interaction between the electron-donating crown ether and the electron-accepting diimide units, particularly the PmI one. Titration experiments show that two Li+ ions are involved in the strengthening of the donor-acceptor interaction. Addition of Li+ ions to NpPmR induces the 1/5DNP38C10 macrocycle to move from the NpI to the PmI unit. The Li+-ion-promoted switching of NpPmR in a 4:1 mixture of CD2Cl2 and CD3COCD3 has also been shown by 1H NMR spectroscopy to involve the mechanical movement of the 1/5DNP38C10 macrocycle from the NpI to the PmI unit, a process that can be reversed by adding an excess of [12]crown-4 to sequester the Li+ ions.     

Manipulating the Through‐Space Spin–Spin Interaction of Organic Radicals in the Confined Cavity of a Self‐Assembled Cage

We show a new approach to manipulating the through‐space spin–spin interaction by utilizing the confined cavity of a self‐assembled M₆L₄ coordination cage. The coordination cage readily encapsulates stable organic radicals in solution, which brings the spin centers of the radicals closer to each other. In sharp contrast to the fact that the radical in solution in the absence of the cage is in a doublet state, in the presence of the cage through‐space spin–spin interaction is induced through cage‐encapsulation effects in solution as well as in the solid state, resulting in the triplet state of the complex. These results were confirmed by ESR spectroscopy and X‐ray crystallography. The quantity of triplet species generated by encapsulation in the cage increases with increasing affinity of the radicals to the cage. We estimated the affinity between several types of guests and the cage in solution by cyclic voltammetry. We also demonstrate that the through‐space interaction of organic radicals within the self‐assembled coordination cage can be controlled by external stimuli such as heat or pH.