Promoted Aggregation of Aß on Lipid Bilayers in an Open Flowing System.

Self-assembly of amyloid-ß (Aß) peptides in nonequilibrium, flowing conditions is associated with pathogenesis of Alzheimer's disease. We examined the role of biologically relevant, nonequilibrium, flowing conditions in the desorption, diffusion, and integration of Aß-lipid assemblies at the membrane surface using a microchannel connected with microsyringes. A 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayer was formed on a glass substrate and incubated in Aß solution under either a quiescent condition (no flow) or flowing condition for 24 h. Although dot-like aggregates (<1 µm) comprising Aß fibrils formed on the DMPC membrane under the quiescent condition, larger plaque-like aggregates formed under the flowing condition, suggesting that nonequilibrium continuous flow governs the cytotoxicity of Aß species. We propose that Aß adsorption on the membrane surface involves spontaneous desorption of Aß-lipid to form self-assembling aggregates, with this accelerated by surface shear forces. These findings suggest that nonequilibrium, flowing conditions influence inter/intra-molecular Aß-fibril formation to trigger formation of amyloid plaques.

Programmable Design of Self-Organized Patterns through a Precipitation Reaction.

Nature uses self-organized spatiotemporal patterns to construct systems with robustness and flexibility. Furthermore, understanding the principles underlying self-organization in nature enables programmable design of artificial patterns driven by chemical energy. The related mechanisms are however not clearly understood because most of these patterns are formed in reaction-diffusion (RD) systems consisting of intricate interaction between diffusion and reaction. Therefore, comprehensive understanding of the pattern formation may provide critical knowledge for developing novel strategies in both natural science and chemical engineering. Liesegang patterns (LPs) are one of the typical programmable patterns. This study demonstrates that appropriate tuning of gel concentration distribution is a key programming factor for controlling LP periodicities. The gel distribution was realized in bi- or multilayered gels constructed by stacking agarose gels of different concentrations. Thus, exceptional LP periodicities were achieved locally in bilayered gels. Furthermore, RD simulations revealed that the nucleation process modulated by the gel distribution determines the LP periodicity in bilayered gels. Finally, based on this concept, desired LP periodicities were successfully realized by programming gel distributions in multilayered gels. Thus, deep insights into the fundamental role of nucleation in designing LPs can lead to the practical applications of LPs and the understanding of self-organization in nature.

Interplay between two radical species in the formation of periodic patterns during a polymerization reaction.

Periodic patterns are ubiquitous in nature and spontaneously form on molecular to cosmic scales by the interplay between reaction and diffusion. Understanding how these patterns form is important to understand the construction rules of nature and apply them in the synthesis of functional artificial materials. This work clarifies how radical (R˙) species affect pattern formation in periodic precipitated and depleted zones during a polymerization process in an agarose gel. When a monomer (Mon) solution was poured on top of the gel doped with an initiator (In) in a test tube, periodic and continuous precipitation occurred near and far away from the solution/gel interface, respectively. In contrast, a system without In exhibited only a continuous band of precipitates beyond a depleted zone without precipitates at a certain distance from the interface. In the depleted region, an inhibitor (Q) added to the solution limited the polymerization triggered by R˙ formed thermally from Mon. With the addition of enough In to overcome the quenching effect of Q, periodic bands appeared near the solution/gel interface. These results suggest the involvement of two independent polymerization processes: (i) polymerization triggered by R˙ formed from In, which is the dominant process up to 100 h and yields periodic structures near the interface. After 100 h, the dominant process is the polymerization triggered by R˙ generated thermally from Mon, which yields a continuous precipitation zone. These two R˙ species compete and generate periodic bands near the interface (<100 h) and a continuous band far away from the interface (>100 h).

Role of Oxidized Lipids in Permeation of H2O2 Through a Lipid Membrane: Molecular Mechanism of an Inhibitor to Promoter Switch.

H2O2 permeation through a cell membrane significantly affects living organisms, and permeation is controlled by the physico-chemical nature of lipids and other membrane components. We investigated the molecular relationship between H2O2 permeation and lipid membrane structure using three oxidized lipids. POVPC and PazePC act as intra- and inter-molecular permeation promoters, respectively; however, their underlying mechanisms were different. The former changed the partition equilibrium, while the latter changed the permeation pathway. PoxnoPC inhibited permeation under our experimental conditions via an intra-molecular configuration change. Thus, both intra- and inter-molecular processes were found to control the role of oxidized lipids as inhibitors and promoters towards H2O2 permeation with different mechanisms depending on structure and composition. Here, we identified two independent H2O2 permeation routes: (i) permeation through lipid membrane with increased partition coefficient by intra-molecular configurational change and (ii) diffusion through pores (water channels) formed by inter-molecular configurational change of oxidized lipids. We provide new insight into how biological cells control permeation of molecules through intra- and inter-molecular configurational changes in the lipid membrane. Thus, by employing a rational design for both oxidized lipids and other components, the permeation behaviour of H2O2 and other ions and molecules through a lipid membrane could be controlled.

Role of Electrolyte in Liesegang Pattern Formation.

Pattern formation based on the Liesegang phenomenon is considered one of the useful models for gaining a mechanistic understanding of spontaneous spatiotemporal pattern formations in nature. However, for more than a century, the Liesegang phenomenon in chemical systems has been investigated by using electrolytes as both the reaction substrate and aggregation promoter, which has obfuscated the role of the electrolyte. Here, we distinguish the electrolyte (Na2SO4) from the reaction substrates (Ag+ ion and citrate), where Na2SO4 does not participate in the reaction step and acts as an aggregation promoter. The addition of Na2SO4 in Ag+-citrate-type Liesegang rings gave well-resolvable clear bands with a larger spacing coefficient. The observed changes were discussed by using the classical DLVO (Derjaguin-Landau-Verwey-Overbeek) theory, where the role of the electrolyte is to shield the electrostatic repulsive interaction among the reaction products. Furthermore, the numerical simulation of the reaction-diffusion equation with different aggregation thresholds reproduced the salt-dependent change in the spacing coefficient. We expect that an understanding of the exact role of the electrolyte as the aggregation promoter reported here will offer novel insight into how nature spontaneously forms beautiful spatiotemporal patterns.

Liesegang Mechanism with a Gradual Phase Transition.

We report a novel and generalized chemical model for the Liesegang mechanism that involves gradual phase transitions of macromolecules, unlike previous models that involved definite and discontinuous phase transitions. As a model system, an agarose gel medium doped with an initiator was contacted with a solution containing monomer 2-methoxyethyl acrylate (MEA), in which monomers diffused into the gel medium and initiated a polymerization reaction. As there is a monomer concentration gradient along the diffusion direction, the degree of polymerization and the corresponding degree of insolubility showed a similar spatial gradient in the reaction medium because molecular solubility gradually changes from soluble to insoluble with an increase in the degree of polymerization. Under this condition with such a spatial gradient in the degree of polymerization, multiple bands satisfying the spacing law were formed by repetitive precipitation and depletion of insoluble poly(2-methoxyethyl acrylate) (PMEA). In contrast to the Liesegang mechanism for salt formation reactions with definite transition points, such as the solubility product and nucleation threshold, our model involves a gradual transition with a nonzero transition width. The width of the transition point would be the governing parameter for the appearance and characteristics of periodic pattern formation. This model with a nonzero transition width is largely generalized and applicable to various processes involving any solubility transition and thus can be used as a generalized Liesegang model that can be applied to any system with both definite and gradual transitions.

One-Directional Fluidic Flow Induced by Chemical Wave Propagation in a Microchannel.

A one-directional flow induced by chemical wave propagation was investigated to understand the origin of its dynamic flow. A cylindrical injection port was connected with a straight propagation channel; the chemical wave was initiated at the injection port. Chemical waves propagated with a constant velocity irrespective of the channel width, indicating that the dynamics of the chemical waves were governed by a geometry-independent interplay between the chemical reaction and diffusion. In contrast, the velocity of the one-directional flow was dependent on the channel width. Furthermore, enlargement of the injection port volume increased the flow velocity and volume flux. These results imply that the one-directional flow in the microchannel is due to a hydrodynamic effect induced in the injection port. Spectroscopic analysis of a pH indicator revealed the simultaneous behavior between the pH increase near the injection port and the one-directional flow. Hence, we can conclude that the one-directional flow in the microchannel with chemical wave propagation was caused by a proton consumption reaction in the injection port, probably through liquid volume expansion by the reaction products and the reaction heat. It is a characteristic feature of the present system that the hydrodynamic flow started from the chemical wave initiation point and not the propagation wavefront, as observed for previous systems.

Propagation Behaviors of an Acid Wavefront Through a Microchannel Junction.

Waves in reaction-diffusion systems yield a wealth of dynamic self-assembling phenomena in nature. Recent studies have been devoted to utilizing these active waves in conjunction with microscale technology. To provide a compass for controlling reaction-diffusion waves in microspaces, we have investigated the propagation behavior of one specific variety of the reaction-diffusion wave: an acid wave that utilizes an autocatalytic proton-production reaction. Furthermore, the acid wave that we have investigated occurs in a microchannel with a junction connecting circular and straight regions. The obtained results were compared with a neutralization wave that involves only a neutralization reaction. The acid wave was ignited by the addition of the appropriate amount of H2SO4 into the circular region that was filled with a substrate solution, where proton-consuming and proton-producing reactions followed a rapid neutralization reaction. At this stage, the wave penetrated and propagated into the channel region. Comparison between the acid and the neutralization waves clarified that the acid wave required a minimum threshold of H2SO4 concentration in order to be ignited and that the propagation of the acid wave was temporarily delayed because of the presence of intermediate chemical reaction steps. Furthermore, the propagation dynamics was found to be tuned through the configuration of the microchannel. The importance of microchannel configuration, especially for systems with a junction connecting different shapes, is discussed in terms of Fick's law and in terms of the proton flux from the circular to the straight regions.

Liesegang patterns engineered by a chemical reaction assisted by complex formation.

Liesegang rings based on a chemical reaction, not a conventional precipitation reaction, have been developed by appropriate design of the nucleation dynamics in a system involving complex formation in a matrix. The periodic and concentric rings consisted of well-dispersed Ag nanoparticles with diameters of a few nanometers. The approach modeled here could be applied to form novel micropatterns out of inorganic salts, metal nanoparticles, organic nanocrystals, or polymeric fibers, and it could also offer a scaffold for novel models of a wide variety of reaction-diffusion phenomena in nature.

Preferential behavior on donating atoms of an ambidentate ligand 2-methylisothiazol-3(2H)-one in its metal complexes.

Five metal complexes of 2-methylisothiazol-3(2H)-one (MIO), [Co(III)(NH3)5(MIO)](3+), [Ru(II)(NH3)5(MIO)](2+), [Ru(III)(NH3)5(MIO)](3+), [Pt(II)Cl3(MIO)](-), and trans-[U(VI)O2(NO3)2(MIO)2], were synthesized, and their structures were determined by single-crystal X-ray crystallography. MIO is an ambidentate ligand and coordinates to metal centers through its oxygen atom in the cobalt(III), ruthenium(III), and uranium(VI) complexes and through its sulfur atom in the ruthenium(II) and platinum(III) complexes. This result suggests that MIO shows preferential behavior on its donating atoms. We also studied the electron-donor abilities of the oxygen and sulfur atoms of MIO. Various physical measurements on the conjugate acid of MIO and the MIO complexes allowed us to determine an acid dissociation constant (pKa) and donor number (DN) for the oxygen atom of MIO and Lever's electrochemical parameter (EL) and a relative covalency parameter (kL) for the sulfur atom.

Microchannel-induced change of chemical wave propagation dynamics: importance of ratio between the inlet and the channel sizes.

The ability to control chemical wave propagation dynamics could stimulate the science and technology of artificial and biological spatiotemporal oscillating phenomena. In contrast to the conventional chemical approaches to control the wave front dynamics, here we report a physical approach to tune the propagation dynamics under the same chemical conditions. By using well-designed microchannels with different channel widths and depths, the propagation velocity was successfully controlled based on two independent effects: (i) a transition in the proton diffusion mode and (ii) the formation of a slanted wave front. Numerical analysis yielded a simple relationship between the propagation velocity and the microchannel configuration, which offers a simple and general way of controlling chemical wave propagation.

Synthesis and some properties of binuclear ruthenocenes bridged by oligoynes: formation of bis(cyclopentadienylidene)cumulene diruthenium complexes in the two-electron oxidation.

The monoynes [Rc*C[triple bond]CRc*] and [Rc'C[triple bond]CRc'] were obtained in improved yields using [Mo(CO)6]/2-FC6H5OH as a catalyst in the alkyne metathesis of [Rc*C[triple bond]CMe] and [Rc'C[triple bond]CMe], respectively (Rc = ruthenocenyl, Rc* = 1'',2'',3'',4'',5''-pentamethylruthenocenyl, and Rc' = 2',3',4',5'-tetramethylruthenocenyl groups). The diynes [Rc*(C[triple bond]C)2Rc*] and [Rc'(C[triple bond]C)2Rc'] were synthesized by the oxidative coupling of the corresponding terminal ethynes in good yields. The triyne [Rc*(C[triple bond]C)3Rc*] and the tetrayne [Rc*(C[triple bond]C)4Rc*] were prepared by the hetero- and homocoupling of [Rc*C[triple bond]CC[triple bond]CH], which was obtained from the reaction of [Rc*C[triple bond]CCHO] with Li[N2CSiMe3], respectively. Although the oxidation waves did not always exhibit a clear two-electron oxidation process, the oxidation potentials shifted to a lower potential with an increase in the number of methyl substituents on the ruthenocenyl ring, and shifted to a higher potential with the increase in the number of C[triple bond]C units; this result is in contrast to that found in the [Rc(CH=CH)(n)Rc] series. The chemical oxidation of [Rc'C[triple bond]CRc'] yielded a stable two-electron-oxidized species, the structure of which was confirmed by X-ray crystallography to be [Ru2(mu2-eta(6):eta(6)-C5Me4C=CC5Me4)(eta-C5H5)2](BF4)2. Changing the substituents (Rc, Rc*, and Rc') had no effect on the chemical oxidation, but in the case of the Rc' series the Me substituent increased the stability of the two-electron-oxidized species in solution. The diyne [Rc*(C[triple bond]C)2Rc*] and the triyne [Rc*(C[triple bond]C)3Rc*] also gave a similar but unstable two-electron-oxidized species. In acetone or acetonitrile, the two-electron-oxidized species of [Rc*C[triple bond]CRc*] and [Rc*(C[triple bond]C)2Rc*] gradually formed the corresponding bis(fulvene)-type complexes. This implies that the two-electron-oxidized species of [Rc*(C[triple bond]C)(n)Rc*] are destabilized with the increasing n.

A new redox-active coordination polymer with cobalticinium dicarboxylate.

A new two-dimensional coordination polymer with cobalticinium 1,1'-dicarboxylate (ccdc) incorporated in the framework has been prepared, the ccdc functioning as unique monoanionic dicarboxylate ligands. The compound shows a high redox activity based on the ccdc units.

Synthesis and redox behavior of ruthenocene-terminated oligoenes: characteristic and stable two-electron redox system and lower potential shift of the two-electron oxidation wave with elongating conjugation.

Ruthenocene-terminated butadienes and hexatrienes were prepared by the Wittig reaction of 3-ruthenocenyl-2-propenals with ruthenocenylmethylphosphonium salts and the Mukaiyama coupling of the propenals, respectively. Cyclic voltammetry of these complexes indicated that they were involved in a stable two-electron redox process. The oxidation potentials for ruthenocene-terminated oligoenes shifted progressively to lower potential with the increasing CH==CH units as follows: Rc--Rc (0.32 V)>RcCH==CHRc (+0.09 V)>Rc(CH==CH)(2)Rc (-0.06 V)>Rc(CH==CH)(3)Rc (-0.07 V), (Rc=ruthenocene). The tendency is in remarkable contrast to that in the successive one-electron redox process. These complexes were chemically oxidized to give stable crystalline solids, whose structures were confirmed by NMR spectroscopy and X-ray analysis to be oligoene analogues of a bis(fulvene) complex, for example, [(eta(5)-C(5)Me(5))Ru[mu(2)-eta(6):eta(6)-C(5)H(4)CH(CH==CH)(n)CHC(5)H(4)]Ru(eta(5)-C(5)Me(5))](2+) (n=1 or 2). The DFT calculation of the two-electron-oxidized species reproduced well the fulvene-complex structure for the ruthenocene moieties. Since both the neutral and oxidized species are stable and chemically reversible, this redox system may be serviceable as a two-electron version of the ferrocene one-electron redox system.