Search

We describe attempts to achieve high throughput of 17[beta]-estradiol (E2) analysis, including the development of an immunocleanup membrane using polyclonal antibodies and an enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies. An epoxy-group-containing monomer, glycidyl methacrylate (GMA), was graft-polymerized onto a porous hollow-fiber membrane. Subsequently, anti-estrogen (ES) antibody, as a ligand, was coupled with the epoxy group. The ligand density ranged from 3.1 to 5.8 mg/g of the GMA-grafted porous hollow-fiber membrane. A 1.0 [micro]g/L E2 solution was forced to permeate through pores rimmed by the anti-ES-antibody-immobilized polymer chains, at a constant permeation rate. A breakthrough curve, that is, the change in the E2 concentration of the effluent penetrating the outside of the hollow fiber with a change of the effluent volume, was determined. Bound E2 in amounts ranging from 0.42 to 0.80 [micro]g was quantitatively eluted with 3-5 mL of methanol in the permeation mode. The higher permeation rate of the E2 solution resulted in the higher overall binding rate of E2 to the anti-ES-antibody-immobilized porous hollow-fiber membrane because of the negligible diffusional mass-transfer resistance of E2 to the antibody.

We describe a bovine serum albumin (BSA)-multilayer-adsorbed porous hollow-fiber membrane as a stationary phase that enables chiral separations at a high resolution and high rate. Epoxy-group-containing graft chains were uniformly immobilized on the surface of pores throughout a porous hollow-fiber membrane by radiation-induced graft polymerization. Subsequently, a diethylamino group as an anion-exchange moiety was introduced to the graft chains, which caused the chains to expand toward the interior of the pores due to mutual electrostatic repulsion. The expanding polymer chains provided multilayer binding sites for BSA as a chiral selector. BSA with a degree of multilayer binding of 4 specifically recognized L-tryptophan with a separation factor of 6.6 during permeation by a mobile phase (Tris-HCl buffer) injected with a racemic solution of DL-tryptophan through the BSA-multilayered porous membrane. In addition, the separation factor was constant irrespective of flow rates of the mobile phase because of negligible diffusional mass-transfer resistance of tryptophan to BSA multilayered by the graft chains.

The N and O K-shells were excited for a series of CH3CO(CH2)(sub n)CN (n = 0 - 3) to investigate the molecular size effects on the site specific photofragmentation of a core excited molecule. O and N atoms were separated by successively inserting a CH2 group between the two atoms.

Proton conductors have potential applications such as fuel cells, electrolysis cells, and sensors. These applications require new materials with high proton conductivity and high chemical stability at intermediate temperatures. Herein we report a series of new hexagonal perovskite-related oxides, Ba 5 R 2 Al 2 SnO 13 ( R = Gd, Dy, Ho, Y, Er, Tm, and Yb). Ba 5 Er 2 Al 2 SnO 13 exhibited a high proton conductivity without chemical doping (e.g., 0.01 S cm -1 at 303 °C), which is attributed to its high proton concentration and diffusion coefficient. The high diffusion coefficient of Ba 5 Er 2 Al 2 SnO 13 can be attributed to the fast proton migration in the octahedral layers. The high proton concentration is attributed to full hydration in hydrated Ba 5 Er 2 Al 2 SnO 13 and the large amount of intrinsic oxygen vacancies in the dry sample, as evidenced by both neutron diffraction and thermogravimetric analysis. Ba 5 Er 2 Al 2 SnO 13 was found to exhibit high chemical stability under wet atmospheres of O 2 , air, H 2 , and CO 2 . High proton conductivity and high chemical stability indicate that Ba 5 Er 2 Al 2 SnO 13 is a superior proton conductor. Ba 5 R 2 Al 2 SnO 13 ( R = Gd, Dy, Ho, Y, Tm, and Yb) exhibited high electrical conductivity in wet N 2 , suggesting that these materials also exhibit high proton conductivity. These findings will open new avenues for proton conductors. The high proton conductivity via full hydration and fast proton migration in octahedral layers in highly oxygen-deficient hexagonal perovskite-related materials would be an effective strategy for developing next-generation proton conductors.

Exiguobacterium sibiricum rhodopsin (ESR) functions as a light-driven proton pump utilizing Lys96 for proton uptake and maintaining its activity over a wide pH range. Using a combination of methodologies including the linear Poisson-Boltzmann equation and a quantum mechanical/molecular mechanical approach with a polarizable continuum model, we explore the microscopic mechanisms underlying its pumping activity. Lys96, the primary proton uptake site, remains deprotonated owing to the loss of solvation in the ESR protein environment. Asp85, serving as a proton acceptor group for Lys96, does not form a low-barrier H-bond with His57. Instead, deprotonated Asp85 forms a salt-bridge with protonated His57, and the proton is predominantly located at the His57 moiety. Glu214, the only acidic residue at the end of the H-bond network exhibits a p K a value of ∼6, slightly elevated due to solvation loss. It seems likely that the H-bond network [Asp85···His57···H 2 O···Glu214] serves as a proton-conducting pathway toward the protein bulk surface.

The Mn 4 CaO 5 cluster, featuring four ligand water molecules (W1 to W4), serves as the water-splitting site in photosystem II (PSII). X-ray free electron laser (XFEL) structures exhibit an additional oxygen site (O6) adjacent to the O5 site in the fourth lowest oxidation state, S 3 , forming Mn 4 CaO 6 . Here, we investigate the mechanism of the second water ligand molecule at the dangling Mn (W2) as a potential incorporating species, using a quantum mechanical/molecular mechanical (QM/MM) approach. Previous QM/MM calculations demonstrated that W1 releases two protons through a low-barrier H-bond toward D1-Asp61 and subsequently releases an electron during the S 2 to S 3 transition, resulting in O •- at W1 and protonated D1-Asp61. During the process of Mn 4 CaO 6 formation, O •- , rather than H 2 O or OH - , best reproduced the O5···O6 distance. Although the catalytic cluster with O •- at O6 is more stable than that with O •- at W1 in S 3 , it does not occur spontaneously due to the significantly uphill deprotonation process. Assuming O •- at W2 incorporates into the O6 site, an exergonic conversion from Mn1(III)Mn2(IV)Mn3(IV)Mn4(IV) (equivalent to the open-cubane S 2 valence state) to Mn1(IV)Mn2(IV)Mn3(IV)Mn4(III) (equivalent to the closed-cubane S 2 valence state) occurs. These findings provide energetic insights into the deprotonation and structural conversion events required for the Mn 4 CaO 6 formation.

Quinone analogue molecules, functioning as herbicides, bind to the secondary quinone site, Q B , in type-II photosynthetic reaction centers, including those from purple bacteria (PbRC). Here, we investigated the impact of herbicide binding on electron transfer branches, using herbicide-bound PbRC crystal structures and employing the linear Poisson-Boltzmann equation. In contrast to urea and phenolic herbicides [Fufezan, C. Biochemistry 2005, 44, 12780-12789], binding of atrazine and triazine did not cause significant changes in the redox-potential ( E m ) values of the primary quinone (Q A ) in these crystal structures. However, a slight E m difference at the bacteriopheophytin in the electron transfer inactive branch (H M ) was observed between the S (-)- and R (+)-triazine-bound PbRC structures. This discrepancy is linked to variations in the protonation pattern of the tightly coupled Glu-L212 and Glu-H177 pairs, crucial components of the proton uptake pathway in native PbRC. These findings suggest the existence of a Q B -mediated link between the electron transfer inactive H M and the proton uptake pathway in PbRCs.

Solid-state reaction (SSR) is a widely adopted method for functional inorganic material syntheses. Unlike intricate systems emerging from chemically unstable precursor usage, the SSR can proceed from stable precursor couples using simple apparatuses. However, this reaction is associated with high temperatures that overcome solid-state diffusion. Moreover, solid-state syntheses of technologically crucial carbides lead to greenhouse gas emissions. Therefore, exploring an extrinsic component to suppress these challenges is vital to confronting global energy and environmental issues. This study reports that the presence of an ordinary element, vanadium (V), changes the routes of the SSR of niobium carbide (NbC), producing NbC efficiently and cleanly. 1000 °C is far below the temperature required to obtain NbC from a precursor couple of Nb 2 O 5 and C, i.e., approximately 1500 °C is required. However, a carbon substitute, vanadium carbide, completely consumed Nb 2 O 5 before reaching 1000 °C and consummated NbC crystallization for 10 h. Furthermore, NbC crystallites were observed using X-ray diffraction from 770 °C, and their formation was primarily accompanied by VNbO 4 , rather than being routed through NbO 2 produced for the Nb 2 O 5 -C combination. The obtained NbC contained V as a dopant in the 15-50% range (NbC:V), and the relative abundance was correlated with the preparation temperature. Mass analyses revealed that the formation of NbC/V is barely associated with greenhouse gas emissions because of the sizable thermodynamic driving force for primarily forming vanadium oxide byproducts. Device performance using NbC/V was also assessed for a standard electrochemical hydrogen evolution reaction., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Blue light using flavin (BLUF) domain proteins are photoreceptors in various organisms. The PixD BLUF domain can adopt two conformations, W91 out and W91 in , with Trp91 either proximal or distal to flavin (FMN). Using a quantum mechanical/molecular mechanical/polarizable continuum model approach, the energetics of charge-separated and biradical states in the two conformations were investigated. In the W91 out conformation, the charge-separated state (FMN •- ) is more stable than the photoexcited state (FMN*), whereas it is less stable due to an electrostatic repulsive interaction with the Ser28 side chain in the W91 in conformation. This leads to a lower activation energy for the charge separation in the W91 out conformation, resulting in a faster charge separation compared to that in the W91 in conformation. In the W91 out conformation, the radical state (FMNH • ) is more stable than FMN •- and forms from FMN •- , leading to reorientation of the Gln50 side chain adjacent to FMN and formation of a hydrogen bond between Gln50 and FMN. Subsequently, a signaling state forms through charge recombination. In contrast, in the W91 in conformation, FMN •- cannot proceed further, returning to the dark-adapted state, as FMNH • is less stable. Thus, formation of the signaling state exclusively occurs in the W91 out conformation.

Contrary to partially substituted systems, WO 3 molecular sieves that exclusively comprise a d 0 transition metal ion and do not possess template ions in the cavity are a new class of materials for photocatalysis owing to their framework structure. Because WO 3 thermodynamically lacks proton-reduction capability, exploring diverse synthetic approaches of other materials is desirable for facilitating utilization as H 2 evolution and water splitting systems. Herein, we report an efficient approach for the protonation of Ag 2 Ta 4 O 11 to afford H 2 Ta 4 O 11 for application as a H 2 molecular sieve. Hydrogen reduction of Ag 2 Ta 4 O 11 at 300 °C and post-treatment using HNO 3 afforded H 2 Ta 4 O 11 . Characterizations of H 2 Ta 4 O 11 , coupled with density functional theory (DFT) calculations, reveal that the intrinsic structure of Ag 2 Ta 4 O 11 is maintained. Moreover, H + is generated from H 2 oxidation and forms OH, and the orientation of OH is parallel to that of the ab plane. Desorption and adsorption of H 2 within H 2 Ta 4 O 11 were achieved by heating H 2 Ta 4 O 11 to above 90 °C. This is attributed to positive thermal expansion, as confirmed by high-temperature X-ray diffraction. H 2 Ta 4 O 11 is an active heterogeneous photocatalyst for the half-reactions of water splitting. Moreover, deuteration experiments of H 2 Ta 4 O 11 in D 2 O suggest its capability as a H 2 -D 2 conversion catalyst. Furthermore, H 2 Ta 4 O 11 functions as an active synthetic precursor for new tantalate materials, the direct synthesis of which is challenging.

High-mobility group box 1 (HMGB1) is a multifunctional protein. Upon injury or infection, HMGB1 is passively released from necrotic and activated dendritic cells and macrophages, where it functions as a cytokine, acting as a ligand for RAGE, a major receptor of innate immunity stimulating inflammation responses including the pathogenesis of cerebral ischemia/reperfusion (I/R) injury. Blocking the HMGB1/RAGE axis offers a therapeutic approach to treating these inflammatory conditions. Here, we describe a synthetic antibody ( SA ), a copolymer nanoparticle (NP) that binds HMGB1. A lightly cross-linked N -isopropylacrylamide (NIPAm) hydrogel copolymer with nanomolar affinity for HMGB1 was selected from a small library containing trisulfated 3,4,6S-GlcNAc and hydrophobic N - tert -butylacrylamide (TBAm) monomers. Competition binding experiments with heparin established that the dominant interaction between SA and HMGB1 occurs at the heparin-binding domain. In vitro studies established that anti-HMGB1- SA inhibits HMGB1-dependent ICAM-1 expression and ERK phosphorylation of HUVECs, confirming that SA binding to HMGB1 inhibits the proteins' interaction with the RAGE receptor. Using temporary middle cerebral artery occlusion (t-MCAO) model rats, anti-HMGB1- SA was found to accumulate in the ischemic brain by crossing the blood-brain barrier. Significantly, administration of anti-HMGB1- SA to t-MCAO rats dramatically reduced brain damage caused by cerebral ischemia/reperfusion. These results establish that a statistical copolymer, selected from a small library of candidates synthesized using an "informed" selection of functional monomers, can yield a functional synthetic antibody. The knowledge gained from these experiments can facilitate the discovery, design, and development of a new category of drug.

Stereoselective synthesis of bicyclic cyclopentanones was achieved by sequential Tf 2 O-catalyzed decarboxylation and intramolecular [3 + 2] cycloaddition reactions of cyclic enol carbonates bearing an alkene unit. Four stereogenic centers in the obtained cyclopentanone were stereoselectively constructed. This method could be applied to the synthesis of various fused bicyclic products in moderate-to-good yields.

The high-resolution structure of heliorhodopsin crystallized at low pH reveals the presence of a planar triangle molecule, acetate, in the inner water cavity. Here, we investigate how the acetate molecule is stabilized at the counterion Glu107 moiety, using molecular dynamics (MD) simulations and a quantum mechanical/molecular mechanical (QM/MM) approach. QM/MM calculations indicate that the density is best described as acetate among triangle acids, including nitric acid and bicarbonate. The calculated protonation state indicates that protonated acetate donates an H-bond to deprotonated Glu107 in the low-pH crystal structure. The observed red-shift of ∼30 nm in the absorption wavelength with p K a ≈ 4 is likely due to the His23/His80 protonation, rather than the Glu107 protonation. MD simulations also show that acetate can exist at the Glu107 moiety only when it is protonated. When ionized, acetate is released from the Glu107 moiety via Asn101 at the channel bottleneck and Arg91 on the intracellular protein surface. These observations could explain how acetate binds at low pH and releases at high pH.

Water is considered integral for the stabilization and function of proteins, which has recently attracted significant attention. However, the microscopic aspects of water ranging up to the second hydration shell, including strongly and weakly bound water at the sub-nanometer scale, are not yet well understood. Here, we combined terahertz spectroscopy, thermal measurements, and infrared spectroscopy to clarify how the strongly and weakly bound hydration water changes upon protein denaturation. With denaturation, that is, the exposure of hydrophobic groups in water and entanglement of hydrophilic groups, the number of strongly bound hydration water decreased, while the number of weakly bound hydration water increased. Even though the constraint of water due to hydrophobic hydration is weak, it extends to the second hydration shell as it is caused by the strengthening of hydrogen bonds between water molecules, which is likely the key microscopic mechanism for the destabilization of the native state due to hydration.

The Lewis acid-catalyzed decarboxylative coupling of cyclic enol carbonates, prepared by the fixation of carbon dioxide onto propargyl alcohols, with silyl enol ethers including ketene silyl acetals, was developed to afford 1,4-dicarbonyl compounds in good-to-high yields. As the plausible reaction mechanism, it was proposed that the decarboxylative formation of an oxyallyl cation intermediate or its equivalent and the sequential nucleophilic addition of silyl enol ethers proceeded to afford 1,4-dicarbonyl products. In addition, the synthetic utility of the obtained-1,4-dicarbonyl compounds was also demonstrated by applying them to the construction of multisubstituted heterocycles.

Free radical-mediated lipid peroxidation (LPO) induces the formation of numerous lipid radicals, which contribute to the development of several oxidative diseases. To understand the mechanism of LPO in biological systems and the significance of these radicals, identifying the structures of individual lipid radicals is imperative. In this study, we developed an analytical method based on liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) and a profluorescent nitroxide probe, N -(1-oxyl-2,2,6-trimethyl-6-pentylpiperidin-4-yl)-3-(5,5-difluoro-1,3-dimethyl-3 H ,5 H -5l4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-7-yl)propanamide (BDP-Pen), for the detailed structural analysis of lipid radicals. The MS/MS spectra of BDP-Pen-lipid radical adducts showed product ions and thus allow the prediction of the lipid radical structures and individual detection of isomeric adducts. Using the developed technology, we separately detected the isomers of arachidonic acid (AA)-derived radicals generated in AA-treated HT1080 cells. This analytical system is a powerful tool for elucidating the mechanism of LPO in biological systems.

Diatoms can use light in the blue-green region because they have chlorophyll c (Chl c ) in light-harvesting antenna proteins, fucoxanthin and chlorophyll a / c -binding protein (FCP). Chl c has a protonatable acrylate group (-CH═CH-COOH/COO - ) conjugated to the porphyrin ring. As the absorption wavelength of Chl c changes upon the protonation of the acrylate group, Chl c is a candidate component that is responsible for photoprotection in diatoms, which switches the FCP function between light-harvesting and energy-dissipation modes depending on the light intensity. Here, we investigate the mechanism by which the absorption wavelength of Chl c changes owing to the change in the protonation state of the acrylate group, using a quantum mechanical/molecular mechanical approach. The calculated absorption wavelength of the Soret band of protonated Chl c is ∼25 nm longer than that of deprotonated Chl c , which is due to the delocalization of the lowest (LUMO) and second lowest (LUMO+1) unoccupied molecular orbitals toward the acrylate group. These results suggest that in FCP, the decrease in pH on the lumenal side under high-light conditions leads to protonation of Chl c and thereby a red shift in the absorption wavelength.

The electron transfer from the oxygen-evolving Mn 4 CaO 5 cluster to the electron acceptor D1-Tyr161 (TyrZ) is a prerequisite for water oxidation and O 2 evolution. Here, we analyzed the electronic coupling in the rate-limiting electron-transfer transitions using a combined quantum mechanical/molecular mechanical/polarizable continuum model approach. In the S 0 to S 1 transition, the electronic coupling between the electron-donor Mn3(III) and TyrZ is small (2 meV). In contrast, the electronic coupling between the dangling Mn4(III) and TyrZ is significantly large (172 meV), which suggests that the electron transfer proceeds from Mn3(III) to TyrZ via Mn4(III). In the S 1 to S 2 transition, the electronic coupling between Mn4(III) and TyrZ is also larger (124 meV) than that between Mn1(III) and TyrZ (1 meV), which favors the formation of the open-cubane S 2 conformation with Mn4(IV) over the formation of the closed-cubane S 2 conformation with Mn1(IV). In the S 0 to S 1 and S 1 to S 2 transitions, the Mn4 d -orbital and the TyrZ π-orbital are hybridized via D1-Asp170, which suggests that D1-Asp170 commonly provides a dominant electron-transfer route.

A double ring expansion strategy for constructing fused 3-benzazepines is described. The oxidative ring expansion of spiroamine compounds with N -chlorosuccinimide and subsequent ring expansion of the resulting ketiminium ion intermediates with trimethylsilyldiazomethane afforded fused 3-benzazepines in a one-pot operation. Importantly, the Dolby-Weinreb enamine, which is a key synthetic intermediate for harringtonine alkaloids, cephalotaxines, can be accessed from commercial materials in only two steps using our developed method.

N-C axially chiral 3-(2-trideuteriomethyl-4,6-dimethylphenyl)-2-ethylquinazolin-4-ones and 3-(2-trideuteriomethyl-4,6-dimethylphenyl)-2-(1-phenylpropan-2-yl)quinazolin-4-ones were prepared in high enantio- and diastereomeric purities (98% ee). These quinazolinone derivatives are isotopic atropisomers based on ortho -CH 3 /CD 3 discrimination and were revealed to possess a slight optical rotation and high rotational stability.

The intelligent transport of materials at interfaces is essential for a wide range of processes, including chemical microreactions, bioanalysis, and microfabrication. Both passive and active methods have been used to transport droplets, among which light-based techniques have attracted much attention because they are noncontact, safe, reversible, and controllable. However, conventional light-driven systems also involve challenges related to low transport ability and instability. Because of these shortcomings, technologies that can transport and manipulate droplets and microsolids on the same surface have yet to be realized. The present work demonstrates a light-driven system referred to as a liquid conveyor that enables the transport of both water droplets and microsolids. After the incorporation of an azobenzene-based molecular motor capable of undergoing photoisomerization into the surface liquid layer of this system, an isomerization gradient was induced by exposure to ultraviolet light emitting diodes that induced flow in this layer. Various parameters were optimized, including the concentration of the molecular motor compound, the light intensity, the viscosity of the liquid layer, and the droplet volume. This process eventually achieved the horizontal transport of droplets in any direction at varied rates. As a consequence of the limited heat buildup, the lack of droplet deformation, and extremely small contact angle hysteresis in this system, microsolids on droplets were also transported. This liquid conveyor is a promising platform for high-throughput omni-liquid/solid manipulation in the fields of biotechnology, chemistry, and mechanical engineering.

In photosystem II (PSII) and photosynthetic reaction centers from purple bacteria (PbRC), the electron released from the electronically excited chlorophyll is transferred to the terminal electron acceptor quinone, Q B . Q B accepts two electrons and two protons before leaving the protein. We investigated the molecular mechanism of quinone exchange in PSII, conducting molecular dynamics (MD) simulations and quantum mechanical/molecular mechanical (QM/MM) calculations. MD simulations suggest that the release of Q B leads to the transformation of the short helix (D1-Phe260 to D1-Ser264), which is adjacent to the stromal helix de (D1-Asn247 to D1-Ile259), into a loop and to the formation of a water-intake channel. Water molecules enter the Q B binding pocket via the channel and form an H-bond network. QM/MM calculations indicate that the H-bond network serves as a proton-transfer pathway for the reprotonation of D1-His215, the proton donor during Q B H - /Q B H 2 conversion. Together with the absence of the corresponding short helix but the presence of Glu-L212 in PbRC, it seems likely that the two type-II reaction centers undergo quinone exchange via different mechanisms.

Identifying the p K a values of aspartic acid (Asp) and glutamic acid (Glu) in active sites is essential for understanding enzyme reaction mechanisms. In this study, we investigated the correlation between the C═O stretching vibrational frequency (ν C═O ) of protonated carboxylic acids and the p K a values using density functional theory calculations. In unsaturated carboxylic acids (e.g., benzoic acid analogues), ν C═O decreases as the p K a increases (the negative correlation), whereas in saturated carboxylic acids (e.g., acetic acid analogues, Asp, and Glu), ν C═O increases as the p K a increases (the positive correlation) as long as the structure of the H-bond network around the acid is identical. The negative/positive correlation between ν C═O and p K a can be rationalized by the presence or absence of the C═C double bond. The p K a shift was estimated from the ν C═O shift of Asp and Glu in proteins on the basis of the negative correlation derived from benzoic acids. The previous estimations should be revisited by using the positive correlation derived in this study, as demonstrated by quantum mechanical/molecular mechanical calculations of ν C═O and electrostatic calculations of p K a on a key Asp85 in the proton-transfer pathway of bacteriorhodopsin.

A silver-catalyzed carbon dioxide fixation reaction into 2-alkynylindole derivatives was developed to afford tricyclic indoles. Carbon dioxide was selectively fixed on the N atom of the indole, and only 6-endo-dig cyclization proceeded under mild reaction conditions. Carboxylation on C3 of the indole was not observed. This method was applicable for a variety of 2-alkynylindoles, and the corresponding products were obtained in high yields without the production of side products.

In photosystem II (PSII), the second-lowest oxidation state (S 1 ) of the oxygen-evolving Mn 4 CaO 5 cluster is the most stable, as the radical form of the redox-active D2-Tyr160 is considered to be a candidate that accepts an electron from the lowest oxidation state (S 0 ) in the dark. Using quantum mechanical/molecular mechanical calculations, we investigated the redox potential ( E m ) of TyrD and its H-bond partner, D2-His189. The potential energy profile indicates that the release of a proton from the TyrD...D2-His189 pair leads to the formation of a low-barrier H-bond. The E m depends on the H + position along the low-barrier H-bond, e.g., 680 mV when the H + is at the D2-His189 moiety and 800 mV when the H + is at the TyrD moiety, which can explain why TyrD mediates both the S 0 to S 1 oxidation and the S 2 to S 1 reduction., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Most low-potential Fe 4 S 4 clusters exist in the conserved binding sequence CxxCxxC (C n C n +3 C n +6 ). Fe(II) and Fe(III) at the first (C n ) and third (C n +6 ) cysteine ligand sites form a mixed-valence Fe 2.5+ ···Fe 2.5+ pair in the reduced Fe(II) 3 Fe(III) cluster. Here, we investigate the mechanism of how the conserved protein environment induces mixed-valence pair formation in the Fe 4 S 4 clusters, F X , F A , and F B in photosystem I, using a quantum mechanical/molecular mechanical approach. Exchange coupling between Fe sites is predominantly determined by the shape of the Fe 4 S 4 cluster, which is stabilized by the preorganized protein electrostatic environment. The backbone NH and CO groups in the conserved CxxCxxC and adjacent helix regions orient along the Fe C n ···Fe C( n +6) axis, generating an electric field and stabilizing the Fe C n (II)Fe C( n +6) (III) state in F A and F B . The overlap of the d orbitals via -S- (superexchange) is observed for the single Fe C n (II)···Fe C( n +6) (III) pair, leading to the formation of the mixed-valence Fe 2.5+ ···Fe 2.5+ pair. In contrast, several superexchange Fe(II)···Fe(III) pairs are observed in F X due to the highly symmetric pair of the CDGPGRGGTC sequences. This is likely the origin of F X serving as an electron acceptor in the two electron transfer branches.

In photosystem II (PSII), Cl - is a prerequisite for the second flash-induced oxidation of the Mn 4 CaO 5 cluster (the S 2 to S 3 transition). We report proton transfer from the substrate water molecule via D1-Asp61 and electron transfer via redox-active D1-Tyr161 (TyrZ) to the chlorophyll pair in Cl - -depleted PSII using a quantum mechanical/molecular mechanical approach. The low-barrier H-bond formation between the substrate water molecule and D1-Asp61 remained unaffected upon the depletion of Cl - . However, the binding site, D2-Lys317, formed a salt bridge with D1-Asp61, leading to the inhibition of the subsequent proton transfer. Remarkably, the redox potential ( E m ) of S 2 /S 3 increased significantly, making electron transfer from S 2 to TyrZ energetically uphill, as observed in Ca 2+ -depleted PSII. The uphill electron transfer pathway was induced by the significant increase in E m (S 2 /S 3 ) caused by the loss of charge compensation for D2-Lys317 upon the depletion of Cl - , whereas it was induced by the significant decrease in E m (TyrZ) caused by the rearrangement of the water molecules at the Ca 2+ binding moiety upon the depletion of Ca 2+ .

The reaction between H 3 + and CO is important in understanding the H 3 + destruction mechanism in the interstellar medium. In this work, thermal rate coefficients for the H 3 + + CO and D 3 + + CO reactions are calculated using ring-polymer molecular dynamics (RPMD) on a high-level machine-learning potential energy surface. The RPMD results agree well with the classical molecular dynamics results, where nuclear quantum effects are completely ignored, whereas the agreement between the RPMD results and the previous quasi-classical trajectory is good only at low temperatures. The calculated [HCO + ]/[HOC + ] product branching ratios decrease as the temperature increases, and the product branching is exclusively determined by the initial collisional orientation, which governs the formation of an ion-dipole complex, H 3 + ···CO or H 3 + ···OC, that dissociates into H 2 + HCO + or H 2 + HOC + , respectively, via a direct mechanism. However, the contribution of the indirect mechanism via the rearrangement between H 3 + ···CO and H 3 + ···OC increases as the temperature increases, although its absolute fraction is small.

The mechanisms governing the long-range electron tunneling from the primary (Q A ) to secondary (Q B ) quinones in photosystem II are clarified by analyzing superexchange pathways through a nonheme Fe complex, using a quantum mechanics/molecular mechanics/polarizable continuum model approach. The electron tunneling rate is evaluated using the Marcus-Levich-Jortner theory considering electronic coupling, energy difference, and Franck-Condon factor. The superexchange Q A → Q B electron tunneling is enhanced by hybridized σ/σ* orbitals of histidines (D2-His214 and D1-His215) via penetration of the wave function into hydrogen bonds with both Q A and Q B . Despite a large energy gap to the intermediate states, the contributions of the histidine σ/σ* orbitals to the superexchange coupling are larger than those of π/π* orbitals. Fe 2+ is not an essential component for the Q A → Q B electron tunneling because hybridized histidine molecular orbitals can be coupled with both Q A and Q B simultaneously in the absence of Fe d orbitals.

Photo-induced crawling motion of a crystal of 3,3'-dimethylazobenzene (DMAB) on gold surfaces having different surface properties and various patterns was studied. DMAB crystals crawl continuously when exposed to UV and visible lights simultaneously from different directions. On a gold surface functionalized by a thiol having a hydroxyl group at the terminal (16-hydroxy-1-hexadecanethiol (HOC 16 SH)), the crystals crawled with a relatively high velocity (ca. 4 μm min -1 ), and they changed the crystal shape while keeping a distinct crystal face. On a gold surface functionalized by a thiol having an alkyl chain terminal (1-hexadecanethiol (C 16 SH)), the crawling was observed with a slower velocity (ca. 1.5 μm min -1 ). However, the shape of the crystals became a droplet-like shape soon after the irradiation started, and the shape persisted during the motion. Light intensity dependence of the crawling velocity of the droplet-like crystal on this surface showed that UV light has stronger dependence for the motion than the visible light. On a substrate with a stripe pattern of alternating C 16 SH-modified gold and hexadecyltrimethylsilane (HDTMS)-modified glass, crystals crawled only on the surface of the C 16 SH-modified gold, which may be due to the wettability hysteresis at the surface. On a substrate with a stripe pattern of HOC 16 SH-modified gold and HDTMS-modified glass, crystals were attracted to the gold side. On a gold substrate with a periodic pattern of different height (ca. 50 nm) but having a uniform treatment with C 16 SH, crystals crawled up and down the steps without significant disturbance at the boundary of the step. Therefore, wettability of the surface has a greater impact on controlling the motion of the crystal than the surface structure. The present results not only unveil the crawling behavior on various surfaces but also offer a guide to controlling the motion toward applications for novel carriage vehicles to transport molecules/objects on a surface.

Elucidating how the intermolecular interactions of a covalently bonded fluorine atom are similar to and different from those of the other halogen atoms will be helpful for a better unified understanding of them. In the present study, the case of hydrogen fluoride is theoretically studied from this viewpoint by using the techniques of electron density analysis, molecular dynamics of liquid, and others. It is shown that the extra-point model, which locates an additional charge site on the line extended from (not within ) the covalent bond and has been adopted for halogen-bonding systems as a key to the generation of proper stability and directionality, works well also in this case. A significantly bent hydrogen-bond configuration, which is characteristic of the intermolecular interactions of hydrogen fluoride, is reasonably well reproduced, meaning that it is a manifestation of the latent halogen-bonding ability, which is hidden by the strongly electronegative nature.

Racemic and optically active 3-(2-deuteriophenyl)-2-(1-phenylpropan-2-yl)quinazoline-4-thiones were prepared. The nuclear magnetic resonance spectra clearly show that they exist as a 1:1 mixture of diastereomers due to the isotopic atropisomerism based on ortho -H/D discrimination (N-C axial chirality) and a chiral carbon.

Perfume solubilization is an important process in the production of commercial products such as beverages, foods, and cosmetics. In the present study, small-angle neutron scattering (SANS) experiments were performed to investigate the solubilization behavior of perfumes in cetyltrimethylammonium bromide (CTAB) micelles. The solubilization of linalool (LL) and l -menthol (MT), which are relatively hydrophilic perfumes, did not change the size of the CTAB micelles although the perfumes were incorporated in the micelles, as indicated by a decrease in scattering length density. On the other hand, the solubilization of d -limonene (LN), a hydrophobic perfume, led to the swelling of CTAB micelles. An internal contrast variation SANS study was performed by the deuteration of CTAB molecules to directly observe the perfumes in the micelles. The radius of d -CTAB micelles solubilizing LL or MT corresponds to that of h -CTAB, which indicates that these perfumes are accommodated in the palisade layers of the micelles and are homogeneously distributed in the micelles. On the other hand, LN formed small droplets, as indicated by the SANS profile, which implies the solubilization of LN molecules in the core of the CTAB micelles. We found that the relatively hydrophilic perfumes (LL and MT) show less impact on the sizes of the cationic micelles in comparison to nonionic micelles. Thus, the internal contrast variation method of SANS allowed the direct observation of the solubilization sites of perfumes with different hydrophilicity-hydrophobicity balances. This method is a powerful tool to determine the solubilization states that affect the solubilization capacity, volatilization, or release speed of perfumes.

Electron energy-loss spectroscopy (EELS) is becoming an important tool in the characterization of polymeric materials. The sensitivity of EELS to changes in the chemical structure of polymeric materials dictates its applicability. In particular, it is important for compositional analysis to have reference spectra of pure components. Here, we report the spectra of the carbon K-edge of six polymers (polyethylene, polypropylene, polybutylene terephthalate, and polylactic acid) including copolymers (styrene acrylonitrile and acrylonitrile butadiene styrene), to be used as reference spectra for future EELS studies of polymers. We have successfully decomposed the carbon K-edge of each of the polymers and assigned the observed peaks to bonding transitions. The spectra have been acquired in standard experimental conditions, and electron beam damage has been taken into account during establishment of spectral-structural relationships. We found that the more commonly available low-energy resolution spectrometers are adequate to chemically fingerprint linear saturated hydrocarbons such as PE, PP, and PLA. We have thus moved a step closer toward creating an atlas of polymer EELS spectra, which can be subsequently used for chemical bond mapping of polymeric materials with nanoscale spatial resolution., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Lipids exhibit functional bioactivities based on their polar and acyl chain properties; humans obtain lipids from dietary plant product intake. Therefore, the identification of different molecular species facilitates the evaluation of biological functions and nutrition levels and new phenotype-modulating lipid structures. As a rapid screening strategy, we performed untargeted lipidomics for 155 agricultural products in 58 species from 23 plant families, wherein product-specific lipid diversities were shown using computational mass spectrometry. We characterized 716 lipid species, for which the profiles revealed the National Center for Biotechnology Information-established organismal classification and unique plant tissue metabotypes. Moreover, we annotated unreported subclasses in plant lipidology; e.g., triacylglycerol estolide (TG-EST) was detected in rice seeds ( Oryza sativa ) and several plant species. TG-EST is known as the precursor molecule producing the fatty acid ester of hydroxy fatty acid, which lowers ambient glycemia and improves glucose tolerance. Hence, our method can identify agricultural plant products containing valuable lipid ingredients.

In photosystem I, two electron-transfer pathways via quinones (A 1A and A 1B ) are merged at the iron-sulfur Fe 4 S 4 cluster F X into a single pathway toward the other two Fe 4 S 4 clusters F A and F B . Using a quantum mechanical/molecular mechanical approach, we identify the redox-active Fe sites in the clusters. In F A and F B , the Fe site, which does not belong to the CxxCxxCxxxCP motif, serves as an electron acceptor/donor. F X has two independent electron acceptor Fe sites for A- and B-branch electron transfers, depending on the Asp-B575 protonation state, which causes the A 1A -to-F X electron transfer to be uphill and the A 1B -to-F X electron transfer to be downhill. The two asymmetric electron-transfer pathways from A 1 to F X and the separation of the electron acceptor and donor Fe sites are likely associated with the specific role of F X in merging the two electron transfer pathways into the single pathway.

The biosynthetic pathway of asparaptine, a naturally occurring inhibitor of angiotensin-converting enzyme (ACE) in vitro , is largely unknown in Asparagus officinalis . To determine which metabolites are involved in the pathway, we performed tandem mass spectrum similarity-based metabolome network analysis using 13 C-labeled and non-labeled valine-fed asparagus calluses. We revealed that S -(2-carboxy- n -propyl)-cysteine as an intermediate and two new metabolites as asparaptine analogues, lysine- and histidine-type conjugates, are involved in the pathway. Asparaptine was therefore renamed asparaptine A (arginine type), and the two analogues were named asparaptines B (lysine type) and C (histidine type). Oral feeding of asparaptine A to a hypertensive mouse breed showed that this metabolite lowers both the blood pressure and heart rate within 2 h and the effect of asparaptine A wears off after 2 days. These results suggest that asparaptine A may not only have effects as an ACE inhibitor but also have β-antagonistic effects.

We report the existence of two distinct oxygen-radical-containing Mn 4 CaO 5/6 conformations with short O···O bonds in the crystal structures of the oxygen-evolving enzyme photosystem II (PSII), obtained using an X-ray free electron laser (XFEL). A short O···O distance of <2.3 Å between the O4 site of the Mn 4 CaO 5 complex and the adjacent water molecule (W539) in the proton-conducting O4-water chain was observed in the second flash-induced (2F) XFEL structure (2F-XFEL), which may correspond to S 3 . By use of a quantum mechanical/molecular mechanical approach, the OH • formation at W539 and the short O4···O W539 distance (<2.3 Å) were reproduced in S 2 and S 3 with reduced Mn1(III), which lacks the additional sixth water molecule O6. As the O •- formation at O6 and the short O5···O6 distance (1.9 Å) have been reported in another 2F-XFEL structure with reduced Mn4(III), two distinct oxygen-radical conformations exist in the 2F-XFEL crystals.

Photosystem I has two active electron-transfer pathways. However, electron transfer occurs primarily along one of the two branches (A-branch) irrespective of the similar protein environments. Here, we report the origin of the A-branch electron transfer, considering the electronic coupling of the pigments and the electrostatic interaction with the protein environments. In the chlorophyll pair [P A P B ], the electronic coupling between P A and P B is large (85 meV) for the highest occupied molecular orbital, forming the electronically coupled dimer [P A P B ] and serving as an initial electron donor. In contrast, the coupling for the lowest unoccupied molecular orbital is small (15 meV), leading to charge transfer from P B to P A upon the [P A P B ] excitation. The electronic coupling between [P A P B ] and the accessory chlorophyll in the A-branch is significantly larger than that in the B-branch. These results indicate that the asymmetry of the electron-transfer activity originates from P A as a chlorophyll epimer.

The batch adsorption behavior of a humanized monoclonal antibody (hIgG2 mAb) with thermoresponsive polymer (TRP)-modified Sepharose Fast Flow sorbents with different compositions of grafted copolymers is described. At high protein loadings, the adsorption with negatively charged copolymer-modified sorbents exhibited S-shaped isotherms in most cases, indicative of unrestricted multilayer adsorption. The adsorption capacity of the negatively charged copolymer-modified sorbents increased with an increase in the applied environmental temperature due to increased protein-sorbent surface hydrophobic and electrostatic interactions. The affinity of the hIgG2 mAb for a positively charged copolymer-grafted sorbent was much lower than that found for the negatively charged copolymer-grafted sorbents at both 20 and 50 °C due to electrostatic repulsive effects. This study has documented that the molecular functionalities of the grafted copolymer can significantly affect the adsorption behavior of this humanized mAb at both 20 and 50 °C with the isothermal dependencies revealing subtle effects due to copolymer composition.

Tuning the rheological properties of surfactant solutions by charge screening is a convenient formulation tool in cosmetic, household, oil recovery, drag-reduction, and thickening applications. Surfactants self-assemble in water, and upon charge screening and core shielding, they grow into long wormlike micelles (WLMs). These are valuable model systems for soft matter physics, and the most explored formulation is hexadecyl-trimethylammonium bromide (CTAB) and sodium salicylate (NaSal). Replacing NaSal with aromatic salts of altered hydrophobicity results in different penetration of the additive in the CTAB micellar core. This altered penetration depth will determine the anisotropic micellar growth that tailors the viscoelastic response. Sodium 4-methylsalicylate (mNaSal) is a higher hydrophobicity alternative to NaSal, requiring less additive to induce strong changes in the viscoelastic properties. Herein, we provide a comparative study of the mNaSal/CTAB system with the reference NaSal/CTAB over a range of temperatures and salt concentrations. The findings from the well-known NaSal/CTAB pair are transferred to the mNaSal/CTAB system, revealing the origins of the WLM solution's viscoelastic properties by discerning contributions from charge screening and micellar core shielding upon small differences in hydrophobicity.

Although the transition between a bilayer and an interdigitated membrane of a surfactant and lipid has been widely known for long, its mechanism remains unclear. This study reveals the transition mechanism of a cationic surfactant, dioctadecyldimethylammonium chloride (DODAC), through experiments and theoretical calculations. Experimentally, the transition from the interdigitated to bilayer structure in the gel phase of DODAC is found to be induced by adding hydrophobic molecules such as n -alkane and its derivatives. Further addition induces a different transition to another bilayer phase. Our theory, considering the competition of the electrostatic interaction between cationic headgroups and the hydrophobic interaction emerging at the alkyl-chain ends exposed to water, reproduces these two phase transitions. In addition, changes in alkyl-chain packing in the membranes at these transitions are reproduced. The underlying mechanism is that the interdigitated membrane is formed at a small additive content due to electrostatic repulsion. As the energetic disadvantage with respect to the hydrophobic interaction becomes dominant as the content increases, the transition to the bilayer occurs at a specific content. The bilayer-bilayer transition at a higher content is induced by the change in the balance of these interactions. Based on a similar concept, we suggest the mechanism of the additive-induced bilayer-interdigitated transition of phospholipids, i.e., neutrally charged (zwitterionic) surfactants.

The O···O distance for a typical H-bond is ∼2.8 Å, whereas the radiation-damage-free structures of photosystem II (PSII), obtained using the X-ray free electron laser (XFEL), shows remarkably short O···O distances of ∼2 Å in the oxygen-evolving Mn 4 CaO 5/6 complex. Herein, we report the protonation/oxidation states of the short O···O atoms in the XFEL structures using a quantum mechanical/molecular mechanical approach. The O5···O6 distance of 1.9 Å is reproduced only when O6 is an unprotonated O radical (O •- ) with Mn(IV) 3 Mn(III), i.e., the S 3 state. The potential energy profile shows a barrier-less energy minimum region when O5···O6 = 1.90-2.05 Å (O •- ↓) or 2.05-2.20 Å (O •- ↑). Formation of such a short O5···O6 distance is not possible when O6 is OH - with Mn(IV) 4 . In the case in which the O5···O6 distance is 1.9 Å, it seems likely that the O radical species exists in the oxygen-evolving complex of the XFEL-S 3 crystals.

Photoelectron spectroscopy of a molecular anion is very useful for investigating the transition state and intermediate regions on the reactive potential energy surfaces of a neutral system. In this work, we theoretically analyzed the previously measured photoelectron spectrum of the formylmethylene anion, HCCHO - . We simulated the photoelectron spectra for both the singlet and triplet states using the semiclassical method with quantum nuclear densities and Franck-Condon factor calculations with harmonic vibrational analysis. We also performed real-time quantum dynamics calculations to elucidate the importance of the Wolff rearrangement process, which leads to the stable product ketene from the carbene intermediate on the neutral singlet potential energy surface.

The synthesis of polycyclic indene derivatives via silver-catalyzed carbon dioxide fixation on 2-alkynylindene derivatives was achieved by nucleophilic addition of the indenyl anion to carbon dioxide involving carbon-carbon bond formation and subsequent intramolecular cyclization to the alkyne part activated by a silver catalyst. This cascade process could be applied to various substrates to obtain the corresponding products in high yields. The endo / exo selectivity of the cyclization could be controlled by the steric or electronic effect of the substituents on the substrates, and 6- endo -selective cyclization was realized to afford α-pyrone-fused indenes.