Molecular Recognition Studies Research Articles

Preparation of Z- l-Phe-OH-NBD imprinted microchannel and its molecular recognition study

An integrated microchip was presented for selective recognition of Z- l-Phe-OH-NBD, using molecular imprinting technique. Molecularly imprinted polymer (MIP) were prepared by copolymerization in the presence of template molecule Z- l-Phe-OH-NBD, in which methacrylic acid and 4-vinylpyridine were used as functional monomers and ethylene dimethacrylate used as crosslinker. Imprinted polymer particles were introduced into a microchannel fabricated with a new material i.e. poly(methylvinylsiloxane) by simply rapid prototyping method. Imprinted effects were evaluated by laser-induced fluorescence (LIF) detection where the results indicated that good selective recognition for Z- l-Phe-OH-NBD in the imprinted polymer was obtained; the adsorption percentage of Z- l-Phe-OH-NBD was 61%. In contrast to conventional molecular imprinting analysis, integration shortened overall analysis time from 4 h to 10 min.

Synthesis of novel, boron-containing cavitands derived from calix[4]resorcinarenes and their molecular recognition of biologically important polyols in Langmuir films

An efficient synthetic route for the synthesis of cavitands derived from calix[4]resorcinarene and its tetrabromo derivative was elaborated. A large-scale preparation was achieved in excellent yield, by replacing the high-boiling solvents with acetone. The tetrabromocavitands were transformed into tetra-boronic acid cavitands via lithiation with butyllithium and reaction with triethylborate. Two lipophilic cavitands bearing four boronic acid residues were demonstrated to form stable Langmuir monolayers at the water–air interface. These cavitand receptors differ in bridging unit between oxygen atoms, i.e. one contains a one-carbon unit and the other a two-carbon unit. l-sorbose, d-galactose, d-glucose, and d-cellobiose were selected for molecular recognition studies using the Langmuir techniques. The unsubstituted tetra- n-undecyl calix[4]resorcinarene was used as a reference receptor compound. Differences in surface potential were diagnostic of the different types of binding forces, which can occur.

Proteomic profiling of platelet proteins by trypsin immobilized self-assembled monolayers digestion chip and protein identification using electrospray ionization tandem mass spectrometry.

Self-assembled monolayers (SAMs) on coinage metal provide versatile modeling systems for studies of interfacial electron transfer, biological interactions, molecular recognition, and other interfacial phenomena. Recently, the bonding of enzyme to SAMs of alkanethiols onto Au electrode surfaces was exploited to produce a bio-sensing system. In this work, the attachment of trypsin to a SAMs surface of 11-mercaptoundecanoic acid was achieved using water soluble 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysulfosuccinimide as coupling agent. Experimental results have revealed that the X-ray Photoelectron Spectroscopy (XPS) C1s core levels at 286.3 and 286.5 eV (C with N), 288.1 eV (amide bond), and 289.3 eV (carboxyl) illustrate the immobilization of trypsin. These data were also in good agreement with Fourier-Transformed Infrared Reflection-Attenuated Total Reflection (FTIR-ATR) spectra for the peaks valued at 1659.4 cm(-1) (amide I) and 1546.6 cm(-1) (amide II). Using electrospray ionization tandem mass spectrometry (ESI-MS/MS) observations, analytical results have demonstrated the platelet proteins digestion of the immobilized trypsin on the functionalized SAMs surface. For such surfaces, platelet proteins were digested on the trypsin-immobilized SAMs surface, which shows the enzyme digestion ability of the immobilized trypsin. The terminal groups of the SAMs structure can be further functionalized with biomolecules or antibodies to develop surface-base diagnostics, biosensors, or biomaterials.

Large-scale homogeneous molecular templates for femtosecond time-resolved studies of the guest–host interaction

Self-assembled monolayer films based on iodobenzoyloxy-functionalized resorc[4]arenes were prepared on gold substrates to serve as model systems for future time-resolved studies of molecular recognition, a mechanism of outstanding importance in bioorganic systems. The film properties were tested using X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM) and imaging ellipsometry. An apparatus for time-resolved electron spectroscopy utilizing femtosecond soft X-ray pulses is capable of detecting iodine core-level photolines and the photoinduced dissociation after ultraviolet illumination. The developed technique holds promise for tracking the temporal evolution of chemical shifts of atomic markers as local probes for the dynamics of the guest–host interaction.

Acyclic Congener of Cucurbituril: Synthesis and Recognition Properties.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Gas-phase ion mobilities and structures of benzene cluster cations (C6H6)n+, n = 2-6.

Benzene clusters are generated by pulsed supersonic beam expansion, ionized by electron impact, mass-selected and then injected into a drift cell for ion mobility measurements in a helium buffer gas. The measured collision cross sections and theoretical calculations are used to determine the structures of the cluster cations (C(6)H(6))(n)(+) with n = 2-6. Density functional theory calculation, at an all-electron level and without any symmetry constraint, predicts that the dimer cation has two nearly degenerate ground state structures with the sandwich configuration more stable than the T-configuration by only 0.07 eV. The ion mobility experiment indicates that only one structure is observed for the mass-selected dimer cation at room temperature. The calculated cross section for the sandwich structure agrees very well (within 2.4%) with the experimental value. For the n = 3-6 clusters, the experiments suggest the presence of at least two structural isomers for each cluster. A Monte Carlo minimum-energy search technique using the 12-site OPLS potential for benzene is used to determine the structures of the lowest-energy isomers. The calculated cross sections for the two lowest-energy isomers of the n = 3-6 clusters agree well with the experimental results. The clusters' structures reveal two different growth patterns involving a sandwich dimer core or a pancake trimer stack core. The lowest-energy isomers of the n = 3-6 clusters incorporate the pancake trimer stack as the cluster's core. The trimer stack allows the charge to hop between two dimers, thus maximizing charge resonance interaction in the clusters. For larger clusters, the appearance of magic numbers at n = 14, 20, 24, 27, and 30 is consistent with the incorporation of a sandwich dimer cation within icosahedral, double icosahedral, and interpenetrating icosahedral structures. On the basis of the ion mobility results and the structural calculations, the parallel-stacked motif among charged aromatic-aromatic interactions is expected to play a major role in determining the structures of multi aromatic components. This conclusion may provide new insights for experimental and theoretical studies of molecular design and recognition involving aromatic systems.

Bioorganometallic Chemistry: Structural Diversity of Organometallic Complexes with Bioligands and Molecular Recognition Studies of Several Supramolecular Hosts with Biomolecules, Alkali‐Metal Ions, and Organometallic Pharmaceuticals

AbstractFor Abstract see ChemInform Abstract in Full Text.

Acyclic congener of cucurbituril: synthesis and recognition properties.

The cucurbit[n]uril (CB[n]) family of macrocycles occupies a prominent role in molecular recognition and self-assembly studies despite the current inability to access specific cucurbit[n]uril homologues, derivatives, and analogues by straightforward tailor-made synthetic procedures. In this paper, we explore an approach that circumvents the challenges posed by the tailor-made synthesis of macrocyclic CB[n] by preparing 1, which functions as an acyclic CB[6] congener. The o-xylylene connections to the glycoluril rings preorganize 1 into the (a,a,a,a)-1 conformation required for binding and reduce its tendency to undergo self-association. We surveyed the binding properties of 1 toward 16 amines (K(a) <or= 1.52 x 10(4) M(-)(1)) and diol, diacid, guanidinium, and pyridinium species in pD 7.4 phosphate-buffered D(2)O. We find that the recognition properties of 1 parallel those of CB[6], binding tightly to alkaneammonium species in water and exhibiting length-dependent selectivity and competitive binding with alkali metals present in solution. Compound 1 binds hexanediammonium ion only 180-fold less tightly than CB[6]. The modular synthesis of 1 suggests synthetic methods toward the preparation of acyclic CB[n] congeners with complex functional groups on the edges of their aromatic rings and cavity volumes similar to CB[7] and CB[8]. In combination, these results suggest that acyclic CB[n] congeners hold promise in molecular recognition and self-assembly studies that complements that of macrocyclic CB[n].

Interactions with Aromatic Rings in Chemical and Biological Recognition.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Bioorganometallic Chemistry: Structural Diversity of Organometallic Complexes with Bioligands and Molecular Recognition Studies of Several Supramolecular Hosts with Biomolecules, Alkali-Metal Ions, and Organometallic Pharmaceuticals

Bioorganometallic chemistry, a nascent area of organometallic chemistry, has recently provided significant advancements in structural diversity and molecular recognition studies. This review shows the various novel structures with bioligands of other colleagues, as well as those from our own studies. In addition, molecular recognition, the cornerstone of how biological systems operate, has now been extended to organometallic, supramolecular host molecules with biologically important guest compounds, including organometallic ionophores for selective recognition of alkali-metal ions. This host−guest molecular recognition chemistry with biologically important compounds occurs by noncovalent interactions, which encompass π−π, hydrophobic, and selective hydrogen bonding. The advent of organometallic pharmaceuticals has further provided unique molecular recognition/computer docking studies with hormone receptor sites that clearly delineate novel, noncovalent processes. The future looks extremely promising for b...

Interactions with aromatic rings in chemical and biological recognition.

Intermolecular interactions involving aromatic rings are key processes in both chemical and biological recognition. Their understanding is essential for rational drug design and lead optimization in medicinal chemistry. Different approaches-biological studies, molecular recognition studies with artificial receptors, crystallographic database mining, gas-phase studies, and theoretical calculations-are pursued to generate a profound understanding of the structural and energetic parameters of individual recognition modes involving aromatic rings. This review attempts to combine and summarize the knowledge gained from these investigations. The review focuses mainly on examples with biological relevance since one of its aims it to enhance the knowledge of molecular recognition forces that is essential for drug development.

Characterization of the 310-helix in model peptides by HRMAS NMR spectroscopy.

A tetra- and a hepta-homopeptide from the C(alpha)-tetrasubstituted Aib (alpha-aminoisobutyric acid) residue were covalently linked to the POEPOP resin by the fragment-condensation approach. The conformational preferences of the two model peptides were determined for the first time on a solid support by means of high-resolution magic angle spinning NMR spectroscopy. The results obtained indicate that the Aib homopeptides adopt a regular 3(10)-helical structure even when they are covalently bound to a polymeric matrix, and thus confirm the remarkable conformational stability of the peptides rich in this amino acid. An ATR-FTIR spectroscopic investigation, performed in parallel, also confirmed that these polymer-bound peptides do indeed adopt a helical conformation. The results of this study open the possibility to exploit the peptide-resin conjugates based on C(alpha)-tetrasubstituted alpha-amino acids as helpful, structurally organized templates in molecular recognition studies or as catalysts in asymmetric synthesis.

The synthesis and studies towards the self-replication of bis(capped porphyrins).

Connecting two facially-protected porphyrins was expected to lead to an equal mixture of laterally-bridged doubly-protected bis-porphyrins; one in which the two porphyrin units were protected on the same face (syn) and one with the two prophyrin units protected on opposite faces (anti). Addition of a co-factor (bidentate ligand) was expected to lead predominantly to the syn-bis-porphyrin by a templated self-replication process. This concept was explored using Baldwin's capped porphyrin. Bis(capped porphyrins) were synthesised in several steps starting from zinc(II) capped porphyrin 2. Nitration of 2 followed by reduction and photo-oxidation yields a mixture of zinc(II) porphyrindiones 7 and 8 that can separated by HPLC. The condensation of 2 molar eq. of zinc(II) porphyrin-7,8-dione 8 with 1,2,4,5-benzenetetramine leads to the formation of a 1:1 mixture of syn- and anti-dizinc(II) bis(7,8-capped porphyrins), 11 and 12, respectively, that have almost identical spectroscopic properties. These two geometric isomers were distinguished by significant differences in their molecular recognition properties. Likewise the syn- and anti-dizinc(II) bis(2,3-capped porphyrins), 9 and 10, respectively, are synthesised from the related zinc(II) capped porphyrin-2,3-dione 7, and were also identified using molecular recognition studies. The molecular recognition properties of these bis(capped porphyrins) were utilised in studies of self-replicating porphyrin systems. The results show that tetraazaanthraceno-bis-porphyrins 9-12 can catalyse their own formation but self-replication was not observed. These results highlight the potential that these interesting hosts have as templates in supramolecular chemistry, synthesis and catalysis.

Facile resolution of racemic terbutaline and a study of molecular recognition through chiral supramolecules based on enantiodifferentiating self-assembly.

An effective resolving agent, (2S, 3S)-di-O-(p-toluoyl) tartaric acid(4), was screened using a 'family' approach to yield direct resolution of (R)-terbutaline (1) with high optical purity and yield. Molecular recognition was studied by X-ray crystallographic analyses of the single crystals of the pair of diastereomeric salts. The more-soluble salt formed a sheet supramolecular structure, and the less-soluble salt formed a columnar supramolecular structure by enantiodifferentiating self-assembly. The water molecule plays an important role during optical resolution, and makes the supramolecular structure of the less-soluble salt more thermodynamically stable than that of the more-soluble salt. Solvent system has little influence on the resolution.

Syntheses and Spectroscopic Properties of Methylbenzoate Derivatives of Tetrabenzoporphyrin, Application to Circular Dichroism Studies

The syntheses, UV-VIS and fluorescence data of two methylbenzoate derivatives of tetrabenzoporphyrins, i.e., 5-p-methoxycarbonylphenyl- tetrabenzoporphyrin (TBPPhCO2Me), 5-p-methoxycarbonylphenyl-10,15,20- triphenyltetrabenzoporphyrin (TPTBPCO 2 Me), and their zinc and magnesium complexes are described. The latter was tested as a bis(zinc-porphyrin) host in the CD-based molecular recognition studies because of its expanded surface compared to the conventional porphyrin rings and its red shifted Soret band with a large extinction coefficient.

34 NMRを用いた分子レベルでの分子間認識機構研究(口頭発表の部)

34 NMRを用いた分子レベルでの分子間認識機構研究(口頭発表の部)

Quantum Mechanical Characterization of Nucleic Acids in Solution: A Linear-Scaling Study of Charge Fluctuations in DNA and RNA

Atom-centered point charges are a convenient and computationally efficient way to approximately represent the electrostatic properties of biological macromolecules. Atomic charges are routinely used in molecular modeling applications such as molecular simulations, molecular recognition, and ligand binding studies and for determining quantitative structure activity relationships. In the present paper a divide-and-conquer linear-scaling semiempirical method combined with a conductor-like screening model is applied to the calculation of charge distributions of solvated DNA and RNA duplexes in canonical A- and B-forms. The atomic charges on A-DNA, B-DNA, and A-RNA duplex decamers are analyzed to characterize the convergence of the linear-scaling method, and the effects of the charge model and semiempirical Hamiltonian. Furthermore, the inter- and intramolecular charge variations on DNA and RNA duplex 72-mers are investigated to gain insight into the influence of conformation, base stacking, and solvent polari...

Syntheses of steroid-based molecularly imprinted polymers and their molecular recognition study with spectrometric detection

Recognition of five steroid compounds, β-estradiol, ethynylestradiol, estradiolbenzoate, testosterone and methyltestosterone were studied using a synthesized molecularly imprinted polymer (MIP). When β-estradiol was used as the template molecule, the polymer was synthesized with methacrylic acid (MAA) as the functional monomer and ethylene glycol dimethacrylate (EGDMA) as the cross linking agent through non-covalent interactions. It is found that the kind of porogen solvent and the polymerization conditions greatly affected the binding ability of a MIP to a certain molecule. Releasing of the template was performed by continuous extraction with methanol containing 10% acetic acid in a Soxhlet extractor. Our results indicated that such carefully synthesized MIP showed specific affinity toward β-estradiol in the adsorption process.

Molecular Recognition Studies on Supramolecular Systems 34. Synthesis of Aromatic Diamino-bridged Bis(β-cyclodextrin)s and their Inclusion Complexation with Dye Molecules

A series of 6,6'-bis( g -cyclodextrin)s with rigid aromatic diamino tethers, i.e. p -phenylenediamino-bridged-bis(6-amino-6-deoxy- g -cyclodextrin) ( 3 ), 4,4'-bianilino-bridged-bis(6-amino-6-deoxy- g -cyclodextrin) ( 4 ) and 3,3'-bianilino-bridged-bis(6-amino-6-deoxy- g -cyclodextrin) ( 5 ), have been synthesized by the reaction of mono[6- O -( p -toluenesulfonyl)]-( g -cyclodextrin) with corresponding materials. The inclusion complexation behavior of native g -cyclodextrin ( 1 ), mono-(6-anilino-6-deoxy)- g -cyclodextrin ( 2 ), and novel bis( g -cyclodextrin) 3 - 5 with some representative dyes, i.e. ammonium 8-anilino-1-naphthalenesulfonate (ANS), Brilliant Green, Methyl Orange, Acridine Red and Rhodamine B, was investigated at 25C in aqueous phosphate buffer solution (pH 7.20) by means of fluorescence, ultraviolet, circular dichroism spectrometry as well as fluorescence lifetime measurement. The spectrophotometric titrations gave the complex stability constants ( K S ) and Gibbs free energy changes ( j G 0 ) for the stoichiometric 1:1 inclusion complexation of hosts examined with dye molecules. As compared with 1 or 2 , bridged bis( g -cyclodextrin)s displayed significantly enhanced binding abilities towards these dyes. Typically, dimer 3 showed the highest binding ability upon inclusion complexation with acridine red affording 17 times higher K S for 3 than for 1 . The molecular binding abilities and selectivities of dyes by bridged bis( g -cyclodextrin)s have been discussed from the viewpoint of induced-fit interaction and multipoint recognition mechanism.

Chiral discrimination in cyclodextrin complexes of amino acid derivatives: beta-cyclodextrin/N-acetyl-L-phenylalanine and N-acetyl-D-phenylalanine complexes.

In a systematic study of molecular recognition of amino acid derivatives in solid-state beta-cyclodextrin (beta-CD) complexes, we have determined crystal structures for complexes of beta-cyclodextrin/N-acetyl-L-phenylalanine at 298 and 20 K and for N-acetyl-D-phenylalanine at 298 K. The crystal structures for the N-acetyl-L-phenylalanine complex present disordered inclusion complexes for which the distribution of guest molecules at room temperature is not resolvable; however, they can be located with considerable confidence at low temperature. In contrast, the complex with N-acetyl-D-phenylalanine is well ordered at room temperature. The latter complex presents an example of a complex in this series in which a water molecule is included deeply in the hydrophobic torus of the extended dimer host. In an effort to understand the mechanisms of molecular recognition giving rise to the dramatic differences in crystallographic order in these crystal structures, we have examined the intermolecular interactions in detail and have examined insertion of the enantiomer of the D-complex into the chiral beta-CD complex crystal lattice.