Molecular Recognition Function Research Articles

The Integral Role of Conjugate Acids in Brønsted Base‐Catalyzed Regiodivergent Synthesis

Catalyst‐controlled diversity‐oriented synthesis (CatDOS) is an important research area for expanding molecular complexities and achieving high atomic economics. Plenty of regiodivergent syntheses have been achieved through metal catalysis, covalent and non‐covalent organocatalysis by controlling the molecular recognition function of the catalysts. However, the development of regiodivergent CatDOS through Brønsted base in organocatalysis was relatively less than others. Numerous studies about Brønsted base organocatalysis have demonstrated the powerful molecular recognition abilities of their cationic conjugate acids (CA) mainly in controlling the stereoselectivity instead of the regioselectivity. This concept review aims to conceptualize a new perspective to consider the potential role of the cationic CA of Brønsted bases for regiodivergent CatDOS. Recent representative examples are selected to demonstrate the potential of cationic CA on site‐selectivity control in single‐bond and multiple‐bond formation reactions. The summarized results show that even CA of common tertiary amines, protic ammonium ions, could affect the regioselectivity in the early‐ or late‐stage step during multiple‐bond formation after initial deprotonation. The results also hinted that the properties and ion‐pairing interactions of CA could be more important than the basicity of bases in controlling regioselectivity. Perspectives and hypotheses for explanation of the mechanism of regioselectivity are also included in this review.

DNA-functionalized metal or metal-containing nanoparticles for biological applications.

The conjugation of DNA molecules with metal or metal-containing nanoparticles (M/MC NPs) has resulted in a number of new hybrid materials, enabling a diverse range of novel biological applications in nanomaterial assembly, biosensor development, and drug/gene delivery. In such materials, the molecular recognition, gene therapeutic, and structure-directing functions of DNA molecules are coupled with M/MC NPs. In turn, the M/MC NPs have optical, catalytic, pore structure, or photodynamic/photothermal properties, which are beneficial for sensing, theranostic, and drug loading applications. This review focuses on the different DNA functionalization protocols available for M/MC NPs, including gold NPs, upconversion NPs, metal-organic frameworks, metal oxide NPs and quantum dots. The biological applications of DNA-functionalized M/MC NPs in the treatment or diagnosis of cancers are discussed in detail.

Preparation of iron porphyrin/calix[8]arene/graphene ternary composites based on molecular recognition function and their dopamine electrochemical sensing properties

<p indent="0mm">In this paper, tetrabiphenylporphyrin iron (FeTBPP) with electrocatalytic activity and <italic>p</italic>-<italic>tert</italic>-butyl calix[8]arene (C[8]A) with specific molecular recognition functions were self-assembled onto highly conductive graphene oxide (GO) by interfacial self-assembled method to obtain FeTBPP/C[8]A/GO composite film. The structural characterization for the composite film showed that the FeTBPP grew on the conjugated plane of GO by π-π interaction, while C[8]A molecules combined with GO by the hydrogen bond. These ensure good dispersion of the two kinds of molecules on the GO template. Compared with the single component films of the two kinds of molecules, the composite films have significantly improved surface morphology and higher conductivity. The electrochemical test showed that the response current is linear with dopamine (DA) concentration, with a wide detection range of 0.1–1000 μM, high sensitivity of 17.6 μA/mmol and LOD of 25.6 nM. More importantly, depending on the anchoring and dispersing effects of GO on FeTBPP and C[8]A, the detection of DA by composite electrode has high stability, reproducibility and selectivity. The sensor was applied to human urine and serum samples, and the highly sensitive detection of DA was successfully realized.

Contribution of molecular chiral mesoporous silica nanoparticles in delivering drugs with chiral recognition ability

Among massive study of mesoporous silica nanoparticles, molecular chiral mesoporous silica nanoparticles (MC-MSN) enjoy great interests recently as it may exert special functions in chiral environment. To elucidate its potential abilities as drug carriers, the present work focused on its prominent advantage of chiral recognition in adsorbing and delivering drug molecules, which mainly covered molecular recognition of racemic drugs and chiral delivery of achiral drug by triggering chiral responses in biological environment. The result turned out that the loading capacity of L-alanine was 1.56-fold higher than that of DL-alanine, reminding that MC-MSN had effective molecular recognition function due to its chirality. Furthermore, the peak area ratio of levorotary ofloxacin/dextral ofloxacin from loaded ofloxacin was obviously higher than ofloxacin, confirming that MC-MSN can molecularly recognize levorotary drug. After loading poorly water-soluble drug indometacin (IMC) into MC-MSN, the carrier delivered IMC with improved anti-inflammation effect based on its chiral recognition effect.

Cold photo-carving of halogen-bonded co-crystals of a dye and a volatile co-former using visible light.

The formation of co-crystals by the assembly of molecules with complementary molecular recognition functionalities is a popular strategy to design or improve a range of solid-state properties, including those relevant for pharmaceuticals, photo- or thermoresponsive materials and organic electronics. Here, we report halogen-bonded co-crystals of a fluorinated azobenzene derivative with a volatile component-either dioxane or pyrazine-that can be cut, carved or engraved with low-power visible light. This cold photo-carving process is enabled by the co-crystallization of a light-absorbing azo dye with a volatile component, which gives rise to materials that can be selectively disassembled with micrometre precision using low-power, non-burning laser irradiation or a commercial confocal microscope. The ability to shape co-crystals in three dimensions using laser powers of 0.5-20 mW-substantially lower than those used for metals, ceramics or polymers-is rationalized by photo-carving that targets the disruption of weak supramolecular interactions, rather than the covalent bonds or ionic structures targeted by conventional laser beam or focused ion beam machining processes.

Aptamer Conjugated Indium Phosphide Quantum Dots with a Zinc Sulphide Shell as Photoluminescent Labels for Acinetobacter baumannii.

Acinetobacter baumannii is a remarkable microorganism known for its diversity of habitat and its multi-drug resistance, resulting in hard-to-treat infections. Thus, a sensitive method for the identification and detection of Acinetobacter baumannii is vital. However, current methods used for the detection of pathogens have not improved in the past decades and suffer from long process times and low detection limits. A cheap, quick, and easy detection mechanism is needed. In this work, we successfully prepared indium phosphide quantum dots with a zinc sulphide shell, conjugated to a targeting aptamer ligand, to specifically label Acinetobacter baumannii. The system retained both the photophysical properties of the quantum dots and the folded structure and molecular recognition function of the aptamer, therefore successfully targeting Acinetobacter baumannii. Confocal microscopy and transmission electron microscopy showed the fluorescent quantum dots surrounding the Acinetobacter baumannii cells confirming the specificity of the aptamer conjugated to indium phosphide quantum dots with a zinc sulphide shell. Controls were undertaken with a different bacteria species, showing no binding of the aptamer conjugated quantum dots. Our strategy offers a novel method to detect bacteria and engineer a scalable platform for fluorescence detection, therefore improving current methods and allowing for better treatment.

Comparison and recent progress of molecular imprinting technology and dummy template molecular imprinting technology.

Molecular imprinting technology for the preparation of polymers with specific molecular recognition function had become one of the current research hotspots. It has been widely applied in chromatographic separation, antibody and receptor mimetics, solid-phase extraction, bio-sensors, and other fields in the last decades. In this study, molecular imprinting technology was summarized from the points of templates and dummy templates, and four typical target analytes were selected to compare the differences between templates and dummy templates. The current status and prospects of molecular imprinting technology were also proposed.

Interfacing DNA and Polydopamine Nanoparticles and Its Applications

AbstractPolydopamine (PDA) is polymerized from dopamine under oxidative and basic conditions. PDA is a biocompatible material with great versatility for coating various surfaces and it can also form nanoparticles. DNA oligonucleotides are highly stable, and they can recognize a diverse range of molecules from complementary nucleic acids, proteins to small molecules and metal ions. To enhance the molecular recognition function of PDA, it is interfaced with DNA and the conjugates have achieved a wide range of applications in biomedical and analytical science. In this review, the chemistry of some catecholamines, including dopamine and PDA, is first briefly introduced and variables in the PDA synthesis are highlighted. Strategies to promote DNA adsorption on PDA are then discussed including the use of low pH and polyvalent metal ions. In addition, covalent attachment of DNA to PDA can be achieved by using amino or thiol‐modified DNA, forming highly stable conjugates. The specific applications of PDA–DNA conjugate are also delineated, including DNA extraction, biosensing, intracellular delivery, and DNA origami. Finally, some problems in the field are discussed, along with a few future research opportunities.

An analytical method to control the surface density and stability of DNA-gold nanoparticles for an optimized biosensor

DNA functionalized gold nanoparticles (DNA-AuNPs) have shown great potential for biosensing as they combine the excellent optical properties of gold nanoparticles and the molecular recognition function of DNA. Since the DNA density determines the assay performance and the stability of the conjugate, a precise control of the surface density of DNA-AuNP is crucial for an optimized biosensor. Here we report a simple assay for quantifying multiple unlabeled DNAs on AuNPs. The assay relies on potassium cyanide (KCN) to first dissolve the AuNPs, which then releases surface bound DNA for quantification through a double-stranded DNA dye. Using this analytical quantification method, we investigated several strategies to control the surface density of DNA-AuNPs. Besides the precise control of DNA density, the stability of DNA-AuNPs after conjugation is also important in developing a biosensor with optimal performance. Without proper storing conditions, DNA-AuNPs are unstable and aggregate over time. To overcome this problem, we developed a long-term storage solution to ensure the stability and quality of DNA-AuNPs after conjugation which would benefit any DNA-AuNP-based biosensor.

Folding perspectives of an intrinsically disordered transactivation domain and its single mutation breaking the folding propensity

Transcriptional regulation is a critical facet of cellular development controlled by numerous transcription factors, among which are E-proteins (E2A, HEB, and E2-2) that play important roles in lymphopoiesis. For example, primary hematopoietic cells immortalisation is promoted by interaction of the conserved PCET motif consisting of the Leu-X-X-Leu-Leu (LXXLL) and Leu-Asp-Phe-Ser (LDFS) sequences of the transactivation domains (AD1) of E-proteins with the KIX domain of CBP/p300 transcriptional co-activators. Earlier, it was shown that the LXXLL motif is essential for the PCET-KIX interaction driven by the PCET helical transition. In this study, we analyzed the dehydration-driven gain of helicity in the conserved region (residues 11–28) of the AD1 domain of E-protein. Particularly, we showed that AD1 structure was dramatically affected by alcohols, but was insensitive to changes in pH or the presence of osmolytes sarcosine and taurine, or high polyethylene glycol (PEG) concentrations and DOPC Liposomes. These structure-forming effects of solvents were almost completely absent in the case of L21P AD1 mutant characterized by weakened interaction with KIX. This indicates that KIX interaction-induced AD1 ordering is driven by PCET motif dehydration. The L21P mutation-caused loss of molecular recognition function of AD1 is due to the mutation-induced disruption of the AD1 helical propensity.

Molecular Imprinting with Functional DNA.

Molecular imprinting refers to templated polymerization with rationally designed monomers, and this is a general method to prepare stable and cost-effective ligands. This attractive concept however suffers from low affinity, low specificity, and limited signaling mechanisms for binding. Acrydite-modified DNA oligonucleotides can be readily copolymerized into acrylic polymers. With molecular recognition and catalytic functions, such functional DNAs are recently shown to enhance the performance of molecularly imprinted polymers (MIPs) in a few ways. First, DNA aptamers are used as macromonomers to enhance binding affinity and specificity of MIPs. Second, DNA can help produce optical signals to follow binding events. Third, imprinting can also improve the performance of catalytic DNA by enhancing its activity and specificity toward the template substrate. Finally, MIP is shown to help aptamer selection. Bulk imprinting, nanoparticle imprinting, and surface imprinting are all demonstrated with DNA. Since both DNA and synthetic polymers are cost effective and stable, their hybrid materials still possess such properties while enhancing the function of each component. This review covers recent developments on the abovementioned aspects of DNA-containing MIPs, a field just emerged in the last five years, and future research directions are discussed toward the end.

Biophysical Characterization Platform Informs Protein Scaffold Evolvability.

Evolving specific molecular recognition function of proteins requires strategic navigation of a complex mutational landscape. Protein scaffolds aid evolution via a conserved platform on which a modular paratope can be evolved to alter binding specificity. Although numerous protein scaffolds have been discovered, the underlying properties that permit binding evolution remain unknown. We present an algorithm to predict a protein scaffold’s ability to evolve novel binding function based upon computationally calculated biophysical parameters. The ability of 17 small proteins to evolve binding functionality across seven discovery campaigns was determined via magnetic activated cell sorting of 1010 yeast-displayed protein variants. Twenty topological and biophysical properties were calculated for 787 small protein scaffolds and reduced into independent components. Regularization deduced which extracted features best predicted binding functionality, providing a 4/6 true positive rate, a 9/11 negative predictive value, and a 4/6 positive predictive value. Model analysis suggests a large, disconnected paratope will permit evolved binding function. Previous protein engineering endeavors have suggested that starting with a highly developable (high producibility, stability, solubility) protein will offer greater mutational tolerance. Our results support this connection between developability and evolvability by demonstrating a relationship between protein production in the soluble fraction of Escherichia coli and the ability to evolve binding function upon mutation. We further explain the necessity for initial developability by observing a decrease in proteolytic stability of protein mutants that possess binding functionality over nonfunctional mutants. Future iterations of protein scaffold discovery and evolution will benefit from a combination of computational prediction and knowledge of initial developability properties.

Molecular-Level Understanding of Selectively Photocatalytic Degradation of Ammonia via Copper Ferrite/N-Doped Graphene Catalyst under Visible Near-Infrared Irradiation

Developing photocatalysts with molecular recognition function is very interesting and desired for specific applications in the environmental field. Copper ferrite/N-doped graphene (CuFe2O4/NG) hybrid catalyst was synthesized and characterized by surface photovoltage spectroscopy, X-ray powder diffraction, transmission electron microscopy, Raman spectroscopy, UV–Vis near-infrared diffuse reflectance spectroscopy and X-ray photoelectron spectroscopy. The CuFe2O4/NG catalyst can recognize ammonia from rhodamine B (RhB) in ammonia-RhB mixed solution and selectively degrade ammonia under visible near-infrared irradiation. The degradation ratio for ammonia reached 92.6% at 6 h while the degradation ratio for RhB was only 39.3% in a mixed solution containing 100.0 mg/L NH3-N and 50 mg/L RhB. Raman spectra and X-ray photoelectron spectra indicated ammonia adsorbed on CuFe2O4 while RhB was adsorbed on NG. The products of oxidized ammonia were detected by gas chromatography, and results showed that N2 was formed during photocatalytic oxidization. Mechanism studies showed that photo-generated electrons flow to N-doped graphene following the Z-scheme configuration to reduce O2 dissolved in solution, while photo-generated holes oxidize directly ammonia to nitrogen gas.

Polyvalent Spherical Nucleic Acids for Universal Display of Functional DNA with Ultrahigh Stability

AbstractFor nanomaterials that are difficult to functionalize by covalent attachment of DNA, we herein communicate a general method taking advantage of the high avidity of polyvalent binding and the 3D structure of densely functionalized spherical nucleic acids (SNAs). Using DNA‐functionalized gold nanoparticles, simple mixing leads to the formation of highly stable conjugates on 11 different materials including metals, metal oxides, metal–organic frameworks, transition‐metal dichalcogenides, nanocarbons, and polymers. The adsorption affinity of SNAs can be over thousand‐fold higher than that of free DNA of the same sequence, and practically irreversible conjugates are formed withstanding various denaturing agents. The surface attachment and molecular recognition functions of DNA are spatially separated, showing a key advantage of SNAs. The functionalized materials possess the properties of both the substrate and the SNA, allowing specific DNA hybridization in buffer and in serum.

Polyvalent Spherical Nucleic Acids for Universal Display of Functional DNA with Ultrahigh Stability.

For nanomaterials that are difficult to functionalize by covalent attachment of DNA, we herein communicate a general method taking advantage of the high avidity of polyvalent binding and the 3D structure of densely functionalized spherical nucleic acids (SNAs). Using DNA-functionalized gold nanoparticles, simple mixing leads to the formation of highly stable conjugates on 11 different materials including metals, metal oxides, metal-organic frameworks, transition-metal dichalcogenides, nanocarbons, and polymers. The adsorption affinity of SNAs can be over thousand-fold higher than that of free DNA of the same sequence, and practically irreversible conjugates are formed withstanding various denaturing agents. The surface attachment and molecular recognition functions of DNA are spatially separated, showing a key advantage of SNAs. The functionalized materials possess the properties of both the substrate and the SNA, allowing specific DNA hybridization in buffer and in serum.

Peptide aptamer-assisted immobilization of green fluorescent protein for creating biomolecule-complexed carbon nanotube device

Carbon nanotubes are a novel material for next-generation applications. In this study, we generated carbon nanotube and green fluorescent protein (GFP) conjugates using affinity binding peptides. The carbon nanotube-binding motif was introduced into the N-terminus of the GFP through molecular biology methods. Multiple GFPs were successfully aligned on a single-walled carbon nanotube via the molecular recognition function of the peptide aptamer, which was confirmed through transmission electron microscopy and optical analysis. Fluorescence spectral analysis results also suggested that the carbon nanotube–GFP complex was autonomously formed with orientation and without causing protein denaturation during immobilization. This simple process has a widespread potential for fabricating carbon nanotube–biomolecule hybrid devices.

A Study of Disorder-to-Order Transition by Characterizing the Binding Partners using a Statistical Potential

It is crucial to understand the biophysical properties of intrinsically disordered proteins (IDPs) and protein regions (IDRs) as they participate in numerous biological functions by exhibiting a multitude of structural conformations and dynamics. While the molecular recognition functions of IDPs/IDRs include pathways to carry out signaling and regulation, the structural heterogeneity of IDPs are highly linked to the amyloid aggregation that is involved in critical human diseases such as Parkinson's disease, Alzheimer's disease, type II diabetes and others. The functional advantages of IDPs/IDRs are primarily facilitated by their disorder-to-order transitions, specifically in short regions, through low affinity binding with a variety of partners. We found that about 21% of the proteins in DisProt have structural models in PDB, either in full or in part. We developed and deployed a novel statistical potential, termed Position Specific Estimated Energy (PSEE), to study the mechanism of free energy change required for disorder-to-order transition, mediated by negative enthalpy change of the system and increased entropy of the surrounding water. PSEE computes the potential of each residue from protein sequence alone using the pairwise thermodynamic interactions and the solvent accessibility of the residues in local neighborhood. In this study of characterizing the partner-binding sites within IDPs/IDRs and their transitions from disorder-to-order, we emphasize on determining the level of energy of the partners that induce the respective binding and, PSEE was effective in segregating the disordered and ordered residues by computing the energy gap in between. Further, we identified the binding region's likelihood of being disordered in its unbound state using a Disorder Predictor (DisPredict) developed by us. DisPredict is a SVM model with optimized radial basis function kernel and optimized threshold that employs a set of distinguishing attributes for disorder and order characterization including the novel PSEE. DisPredict, PSEE and our novel mechanism of partner-based identification of binding regions together, can assist in the experiments for drug discovery exploiting binding sites within IDPs/IDRs.

Multivalent foldamer-based affinity assay for selective recognition of Aβ oligomers

Mimicking the molecular recognition functionality of antibodies is a great challenge. Foldamers are attractive candidates because of their relatively small size and designable interaction surface. This paper describes a sandwich type enzyme-linked immunoassay with a tetravalent β-peptide foldamer helix array as capture element and enzyme labeled tracer antibodies. The assay was found to be selective to β-amyloid oligomeric species with surface features transiently present in ongoing aggregation. In optimized conditions, with special emphasis on the foldamer immobilization, a detection limit of 5 pM was achieved with a linear range of 10–500 pM. These results suggest that protein mimetic foldamers can be useful tools in biosensors and affinity assays.

Molecular imprinting functionalized silica xerogel for selective recognition of levorotatory ofloxacin

In the present work, molecular imprinting silica xerogel (MISX) with selective recognition function aiming to regulate drug therapy was synthesized using biomimetic method with poly(ethyleneimine)s (PEIs) as the polymer template and levorotatory ofloxacin (LOFL) as recognition template. Ultraviolet spectroscopy wavelength scanning was used to test the removal process of LOFL, and characteristics of selective loading ofloxacin (OFL) into MISX were investigated using Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Molecular recognition functionality of MISX was intensively studied, including OFL loading and release. The results suggested that MISX possessed ability to recognize and selectively adsorb LOFL into MISX in OFL aqueous solution. Amorphous phase of adsorbed molecules contributed to molecular recognition because amorphous state increased the stability of LOFL that were selectively adsorbed into MISX, which induced stronger hydrogen bonding formed between LOFL and MISX so as to improve LOFL recognition ability. In vitro release revealed that OFL-MISX tablet initially released LOFL and later gradually OFL into dissolution medium. Thus conversion of drug release with different pharmacological activity had special value in delivering systems.

Electrochemical Molecular Recognition System Utilizing Current Amplification of Metal Complexes Assembled on Gold Nanoparticles

Introduction Because gold nanoparticles (GNP) have a characteristic color and the color changes by their aggregation, the optical molecular recognitions are widely investigated by using a color change. However, we reported that the electrochemical sugar recognition system using tris(acetylacetonato)ruthenium complex and boronic acid assembled on the GNP showed a glucose-selectivity and higher sensitivity in 10-6 M order than optical recognition.1) It is considered that one of the reasons of high sensitivity may be the amplification of the reduction current of tris(acetylacetonato)ruthenium complex by assembly on the GNP. This electrochemical molecular recognition system has a great advantage that the molecular recognition site can exchange to others according to the target molecules. Furthermore, the metal complex can also change to the others according to avoid the disturbance from coexistent redox active species. That is, the redox potential can select by changing the redox active complex. Purpose For the purpose of the verification of the current amplification and the utility of this electrochemical molecular recognition system using the GNP, in this work, ferrocene (Fc), tris(acetylacetonato)ruthenium ([Ru(acac)3]), bis(acetylacetonato)ruthenium ([Ru(acac)(BP)2], BP = pyridine boronic acid), and bipylidine ruthenium ([Ru(py)(bpy)(trpy)]) were assembled on the GNP as electroactive site. Boronic acid (BA) for recognition of sugar, dipicolilamine (DPY) for recognition of phosphate derivatives (ADP, ATP, etc.), succinimide (SCI) for recognition of dopamine (DA), and crown ether (CE) for recognition of cesium ion were assembled on the GNP. Thus, the six kinds of GNP complexes (GNP/[Ru(acac)(BP)2]/BA, GNP/Fc/BA, GNP/[Ru(py)(bpy)(trpy)]/BA, GNP/[Ru(acac)3]/DPY, GNP/[Ru(acac)3]/CE), and GNP/[Ru(acac)3]/SCI) prepared and investigated molecular recognition functions. Osteryoung square wave voltammetry (OSWV) or differential pulse voltammetry (DPV) were used for the electrochemical measurements. Results 1. Current Amplification: In order to confirm the current amplification, the concentration dependence of the reduction current of the [Ru(acac)3] and of GNP/[Ru(acac)3] were measured and their slopes were compared. The slope for GNP/[Ru(acac)3] was ca. 29 times larger than that for [Ru(acac)3]. For oxidation current of ferrocene, the slope for GNP/Fc was ca. 7 times larger than that for Fc. In the silver nanoparticle system, further current amplification was observed, so it is considered that the kind of nanoparticle seem to affect the current amplification. The mechanism of the current amplification is not yet clear, but the electron tunneling due to the electron conductivity of the GNP may be considered as main factor of the current amplification mechanism.2. Molecular Recognition: In the electrochemical measurement, the current values decreased by adding the target molecules. In the case of sugar recognition by BA, GNP/[Ru(acac)3]/BA showed highest sensitivity among three types of GNP complexes (GNP/[Ru(acac)3]/BA, GNP/Fc/BA, and GNP/[Ru(py)(bpy)(trpy)]/BA). Sensitivity of [Ru(py)(bpy)(trpy)] was slightly less than two metal complexes. Each complex showed different selectivity for three kinds of sugars. For GNP/[Ru(acac)(BP)2]/BAsystem (recognition site (BP) is on the Ru complex), sensitivity is higher than that of GNP/[Ru(acac)3]/BA, although the selectivity did not show for three kinds of sugar. GNP/[Ru(acac)3]/(DPY+Zn2+) could be recognized phosphate derivatives such as AMP, ADP, and ATP with high sensitivity (10-6 M order) in the presence of Zn2+. Furthermore, slight ATP selectivity was obtained. GNP/[Ru(acac)3]/CE showed an excellent sensitivity for cesium ion (10-9 M order). In this case, it was consider that the aggregation caused by CE ring sandwiching for cesium ion increased the sensitivity, because the CE (18-crown-6) ring size was smaller than cesium ion diameter. In this case, two types of GNP (type A and type B) complexes were prepared. In type A, CE probe has longer alkyl chain than [Ru(acac)3] probe, and in type B CE probe has same length as [Ru(acac)3] probe. Type A may aggregate more than type B, because there is no steric obstruction by [Ru(acac)3]. As a result, the detection limit of the type A is 0.4 nM and 10 times as sensitive as type B. For the recognition of dopamine, the aggregation of GNP is brought about by the complexation of dopamine in the presence of Fe3+. As a result, high sensitivity was attained (LOD = 3 nmol dm-3).By using this electrochemical molecular recognition system, target molecules could be recognized with high sensitivity of mM – nM. The sensitivity and selectivity was depending on the kind of electroactive metal complex. Thus, it was verified the utility of this electrochemical molecular recognition system using metal complexes assembled on gold nanoparticles. 1) A.Endo, M. Kimura, T. Hashimoto, and T. Hayashita, Anal. Methods, 2014, 6(22), 8874-8877. Figure 1