Weak Complexes Research Articles

Complexity and weak integration promote the diversity of reef fish oral jaws

Major trade-offs often manifest as axes of diversity in organismal functional systems. Overarching trade-offs may result in high trait integration and restrict the trajectory of diversification to be along a single axis. Here, we explore the diversification of the feeding mechanism in coral reef fishes to establish the role of trade-offs and complexity in a spectacular ecological radiation. We show that the primary axis of variation in the measured musculo-skeletal traits is aligned with a trade-off between mobility and force transmission, spanning species that capture prey with suction and those that bite attached prey. We found weak or no covariation between about half the traits, reflecting deviations from the trade-off axis. The dramatic trophic range found among reef fishes occurs along the primary trade-off axis, with numerous departures that use a mosaic of trait combinations to adapt the feeding mechanism to diverse challenges. We suggest that morphological evolution both along and independent of a major axis of variation is a widespread mechanism of diversification in complex systems where a global trade-off shapes major patterns of diversity. Significant additional diversity emerges as systems use weak integration and complexity to assemble functional units with many trait combinations that meet varying ecological demands.

A study of the Ganea conjecture for topological complexity by using weak topological complexity

Abstract In this paper, we provide sufficient conditions for a space X to satisfy the Ganea conjecture for topological complexity. To achieve this, we employ two auxiliary invariants: weak topological complexity in the sense of Berstein–Hilton, along with a certain stable version of it. Several examples are discussed.

Biocompatible and hydrophilic copper-complexed polyvinyl alcohol coating for antifogging surfaces

Visibility is decreased when fog accumulates on the clear surface of optical devices. It is quite desirable to design the surface with antifogging properties. The current study used a dip coating process to prepare copper-incorporated polyvinyl alcohol (PVA) hydrophilic coating on the hydroxylated glass substrate. The formation of the PVA-Cu complex by the hydroxyl group was determined by FTIR and XPS methods. The surface morphology, adhesion test, wettability behavior, and cytotoxicity were investigated by SEM, cross-cut tape, contact angle measurement, and MTT experiment. By varying the CuCl2 concentration (0.0125–0.0625 M), the durability and adhesion of the coating were improved, as evidenced by its minimal mass loss and water uptake. The optimum coating condition showed a thickness of about 24.0 ± 0.7 μm and a good optical transmittance of over 90 %. Below 0.0375 M, the coating stability and water resistance could not be achieved due to the weak complexation of Cu with the PVA coating. In contrast, the PVA-Cu3 coating (0.0375 M, Cu2+ ions) was identified as an optimized condition for improved antifogging performance due to the effective complexation of Cu with the PVA matrix while maintaining the hydrophilicity and wettability behavior. Furthermore, no cytotoxicity was observed by L929 cell lines in response to the prepared coating. The current study results revealed that the adhesive, hydrophilic PVA-Cux coating with a contact angle of less than 62° might demonstrate strong antifogging properties and find its usage for endoscopic applications.

Comparative QSAR and q-RASAR modeling for aquatic toxicity of organic chemicals to three trout species: O. Clarkii, S. Namaycush, and S. Fontinalis

Oncorhynchus clarkii, Salvelinus fontinalis, and Salvelinus namaycush are vital trout species in North America, crucial for maintaining ecological balance, economic stability, and human health. These species thrive in cold, unpolluted waters and are highly vulnerable to contaminants. Given the rapid proliferation of industrial organic chemicals, traditional in vivo toxicity testing methods are inadequate to ensure timely and comprehensive risk assessments. Therefore, we employed in silico tools, namely Quantitative Structure-Activity Relationship (QSAR) and Quantitative Read-Across Structure-Activity Relationship (q-RASAR), to efficiently predict the aquatic toxicity of chemicals. Utilizing acute median lethal concentration (LC50) data from the US EPA’s ToxValDB, we developed the first-ever species-specific QSAR and q-RASAR models. The q-RASAR models outperformed traditional QSAR models by achieving higher internal and external statistical quality for each species. Key toxicity-determining descriptors included electrotopological state indices, autocorrelation descriptors, and similarity-based RASAR descriptors. For O. clarkii, the presence of chlorine atoms and rotatable bonds significantly influenced toxicity. S. fontinalis toxicity was strongly affected by polarizability, and van der Waals volumes, while S. namaycush showed sensitivity to weak hydrogen bond acceptors and topological complexity. The models predicted the toxicity of 1172 external compounds, identifying the most and least toxic chemicals for each species. This study not only offers the first comprehensive q-RASAR models for predicting trout species-specific toxicity but also provides novel insights into species-specific toxicological modes of action. The results contribute significantly to chemical screening and prioritization in aquatic risk assessments, effectively filling critical data gaps and advancing predictive modeling techniques.

Ion Association and Hydration of Some Heavy-Metal Nitrate Salts in Aqueous Solution.

Aqueous solutions of four heavy-metal nitrate salts (AgNO3, TlNO3, Cd(NO3)2 and Pb(NO3)2) have been studied at 25 °C using broadband dielectric relaxation spectroscopy (DRS) at frequencies 0.27 ≤ ν/GHz ≤ 115 over the approximate concentration range 0.2 ≲ c/mol L-1 ≲ 2.0 (0.08 ≲ c/mol L-1 ≲ 0.4 for the less-soluble TlNO3). The spectra for AgNO3, TlNO3, and Pb(NO3)2 were best described by assuming the presence of three relaxation processes. These consisted of one solute-related Debye mode centered at ∼2 GHz and two higher-frequency solvent-related modes: one an intense Cole-Cole mode centered at ∼18 GHz and the other a small-amplitude Debye mode at ∼500 GHz. These modes can be assigned, respectively, to the rotational diffusion of contact ion pairs (CIPs), the cooperative relaxation of solvent water molecules, and its preceding fast H-bond flip. For Cd(NO3)2 solutions an additional solute-related Debye mode of small-amplitude, centered at ∼0.5 GHz, was required to adequately fit the spectra. This mode was consistent with the presence of small amounts of solvent-shared ion pairs. Detailed analysis of the solvent modes indicated that all the cations are strongly solvated with, at infinite dilution, effective total hydration numbers (Zt0 values) of irrotationally bound water molecules of ∼5 for both Ag+ and Tl+, ∼10 for Pb2+, and ∼20 for Cd2+. These results clearly indicate the presence of a partial second hydration shell for Pb2+(aq) and an almost complete second shell for Cd2+(aq). However, the hydration numbers decline considerably with increasing solute concentration due to ion-ion interactions. Association constants for the formation of contact ion pairs indicated weak complexation that varies in the order: Tl+ < Ag+ < Pb2+ < Cd2+, consistent with the charge/radius ratios of the cations and their Gibbs energies of hydration. Where comparisons were possible the present constants mostly agreed well with the rather uncertain literature values.

Site‐selective Photoredox‐Catalyzed Late‐stage Benzylic Hydrogen Isotope Exchange

A highly regioselective visible light photoredox‐catalyzed hydrogen isotope exchange (HIE) of benzylic positions in both simple and complex molecules is reported. The process follows a dual catalytic approach using an acridinium photocatalyst in combination with a thiol‐based hydrogen atom transfer catalyst, while the use of D2O as an isotope source ensures operational simplicity and cost‐effectiveness. High reactivity has been achieved for electron‐rich benzylic positions. Moreover, targeted radical formation enables unprecedented selective HIE on intramolecular competing benzylic and alpha to heteroatom positions with moderate to excellent deuterium incorporation. The utility of the reaction was demonstrated on the late‐stage HIE of several natural compounds and drug derivatives. Experimental studies and density functional theory (DFT) calculations suggested a single electron transfer (SET) mechanism followed by deprotonation to generate the benzylic radical, and revealed the importance of halogenated solvents or additives. Upon a weak complexation of the halogenated species to the substrate, an oxidation potential lowering effect is induced, as well as a stabilization of the radical‐cation species through spin delocalization.

Site-selective Photoredox-Catalyzed Late-stage Benzylic Hydrogen Isotope Exchange.

A highly regioselective visible light photoredox-catalyzed hydrogen isotope exchange (HIE) of benzylic positions in both simple and complex molecules is reported. The process follows a dual catalytic approach using an acridinium photocatalyst in combination with a thiol-based hydrogen atom transfer catalyst, while the use of D2O as an isotope source ensures operational simplicity and cost-effectiveness. High reactivity has been achieved for electron-rich benzylic positions. Moreover, targeted radical formation enables unprecedented selective HIE on intramolecular competing benzylic and alpha to heteroatom positions with moderate to excellent deuterium incorporation. The utility of the reaction was demonstrated on the late-stage HIE of several natural compounds and drug derivatives. Experimental studies and density functional theory (DFT) calculations suggested a single electron transfer (SET) mechanism followed by deprotonation to generate the benzylic radical, and revealed the importance of halogenated solvents or additives. Upon a weak complexation of the halogenated species to the substrate, an oxidation potential lowering effect is induced, as well as a stabilization of the radical-cation species through spin delocalization.

Density functional modeling of ternary Am(III) hydroxo complexes with Ca or Mg counterions. Do Mg stabilized species exist?

We carried out density functional computations to investigate experimentally suggested ternary Ca–Am(III)–OH and possible Mg–Am(III)–OH complexes in water. We confirmed the experimental stoichiometry for the Ca complexes and their relative stability. For the Mg complexes, we find comparable or weaker complexation. This finding is in agreement with experimental observations. We demonstrate that explicit solvation of counterions is important when comparing Ca and Mg species. For the Ca complexes this has a minimal effect on their relative stability. Contrariwise, Mg complexes exhibit a lower stability and are highly sensitive to explicit short-range solvation effects. Explicit Mg2+ solvation significantly altered both absolute and relative formation energies compared to a simpler model. These findings highlight the crucial role of incorporating explicit short-range solvation effects in accurate computational modeling when small and highly charged ions are treated.

Hybrid deconvolution method based on mode composition beamforming for separating sound sources with different motion modes

The presence of sound sources that rotate can cause interference with stationary acoustic imaging, especially if the intensity of the rotating sound source is strong. Vice versa, stationary sound sources can also interfere with rotational acoustic imaging. Current algorithms for separating and locating rotating and stationary sound sources have problems such as weak separation capabilities, complex calculations, and limited array layouts. To address these challenges more effectively, a frequency-domain hybrid deconvolution method based on modal composition beamforming is proposed to separate and localize rotating and stationary sound sources. This algorithm operates within the frequency domain and is not restricted by array layout or the tonal single-frequency nature of sound sources. First, the point spread function and cross-point spread function matrices of the array are derived based on the modal transfer function. Then, a system of linear equations is constructed to separate rotating and stationary sound sources. Finally, the sound source separation and localization problems are solved through Gaussian Seidel and sparse-constrained deconvolution, respectively. Compared with the virtual rotating array method combined with matrix completion, simulation and experimental results demonstrate that this method can accurately locate and separate rotating and stationary sound sources, even when there is a substantial difference in intensity between rotating and stationary sound sources.

Porphyrin complex-based reversible fluorescent film sensor for differentiating and detecting sarin mimics vapor

This study presents a TAPP-based fluorescent sensor for diethylchlorophosphate (DCP), a surrogate for sarin, addressing the critical challenge of detecting nerve agents. The sensor can form a reversible weak bond interaction with the PO group in sarin by using the reversible weak bond complexation mechanism in the porphyrin cavity, which is the key to realize the reversible function of the sensor. In this study, we constructed a fluorescence probe that combines the advantages of physical process and chemical reaction process sensing, which not only ensures selectivity, but also realizes continuous and reversible real-time detection of DCP. The sensor demonstrates excellent photochemical stability and sensitivity, with an actual detection limit of 10 ppt and a theoretical detection limit of 1 ppt. In addition, it can differentiate challenging interferents like HCl through response kinetics, offering a practical, cost-effective, and environmentally sustainable solution for nerve agent detection in high-risk environments.

PICKLE and HISTONE DEACETYLASE6 coordinately regulate genes and transposable elements in Arabidopsis.

Chromatin dynamics play essential roles in transcriptional regulation. The chromodomain helicase DNA-binding domain 3 chromatin remodeler PICKLE (PKL) and HISTONE DEACETYLASE6 (HDA6) are required for transcriptional gene silencing, but their coordinated function in gene repression requires further study. Through a genetic suppressor screen, we found that a point mutation at PKL could partially restore the developmental defects of a weak Polycomb repressive complex 1 (PRC1) mutant (ring1a-2 ring1b-3), in which RING1A expression is suppressed by a T-DNA insertion at the promoter. Compared to ring1a-2 ring1b-3, the expression of RING1A is increased, nucleosome occupancy is reduced, and the histone 3 lysine 9 acetylation (H3K9ac) level is increased at the RING1A locus in the pkl ring1a-2 ring1b-3 triple mutant. HDA6 interacts with PKL and represses RING1A expression similarly to PKL genetically and molecularly in the ring1a-2 ring1b-3 background. Furthermore, we show that PKL and HDA6 suppress the expression of a set of genes and transposable elements (TEs) by increasing nucleosome density and reducing H3K9ac. Genome-wide analysis indicated they possibly coordinately maintain DNA methylation as well. Our findings suggest that PKL and HDA6 function together to reduce H3K9ac and increase nucleosome occupancy, thereby facilitating gene/TE regulation in Arabidopsis (Arabidopsis thaliana).

Rolling Bearing Fault Diagnosis Based on MResNet-LSTM

In response to the challenges of weak fault characteristics and complex and variable working conditions of roll-ing bearings in strong noise environments, a diagnostic methodology is proposed. This method integrates a multi-scale residual neural network (MResNet) and a long short-term memory (LSTM) neural network to achieve fault diagnosis of bearings under both constant and variable rotational speed working conditions. First, complete an ensemble empirical mode decomposition with adaptive noise (CEEMDAN) that is applied for vibration signal denoising. Secondly, a dropout layer is introduced between multi-scale residual blocks to prevent net-work overfitting, and the powerful time series information capture ability of LSTM is combined to improve di-agnostic accuracy. Finally, experimental verification is conducted using constant and variable speed bearing data sets. The results show that the proposed approach maintains strong diagnostic capabilities when the rotat-ing speed conditions change, and the signal is heavily polluted by noise.

Unexpected weakened formation of disinfection byproducts and enhanced production of halates by cupric oxide during chlorination of peptide-bound aspartic acid

Under the condition that the residual chlorine is guaranteed, the biofilm still thrives in drinking water distribution systems through secreting a large number of extracellular polymeric substances (EPS), in which protein components are the primary precursor of disinfection byproducts (DBPs), mostly in the form of combined amino acids. The aim of this study is to investigate the action of CuO on the formation of halates (XO3−, ClO3− and BrO3−) and DBPs (trihalomethanes, THMs; haloacetonitriles, HANs) with aspartic acid tetrapeptide (TAsp) as protein surrogate. The presence of CuO promoted the self-decay rather than TAsp-induced decay of oxidants, resulting in an increase in XO3− yield and a decrease in DBPs yield. It was CuO-induced weaker production of cyanoacetic acid and 3-oxopropanoic acid that induced the decreased yields of HANs and THMs, respectively. The FTIR and Raman spectra indicate a weak complexation between CuO and TAsp. Given this, the CuO-HOX/OX− complexes were inferred to be reactive to HOX/OX− but less reactive to TAsp. The study helps to better understand the formation of XO3− and DBPs during the chlorination of EPS, and propose precise control strategies when biofilm boosts in water pipes.

Polyaromatic Hydrocarbon Inclusion Complexes with 2-Hydroxylpropyl-β/γ-Cyclodextrin: Molecular Dynamic Simulation and Spectroscopic Studies.

In aqueous and solid media, 2-HP-β/γ-CD inclusion complexes with poly aromatic hydrocarbon (PAH) Phenanthrene (PHN), Anthracene (ANT), Benz(a)pyrene (BaP), and Fluoranthene (FLT) were investigated for the first time. The inclusion complexes were characterized and investigated using fluorescence and 1HNMR spectroscopy. The most prevalent complexes consisting of both guests and hosts were those with a 1:1 guest-to-host ratio. The stability constants for the complexes of PHN with 2-HP-β-CD and 2-HP-γ-CD were 85 ± 12 M-1 and 49 ± 29 M-1, respectively. Moreover, the stability constants were found to be 502 ± 46 M-1 and 289 ± 44 M-1 for the complexes of ANT with both hosts. The stability constants for the complexes of BaP with 2-HP-β-CD and 2-HP-γ-CD were (1.5 ± 0.02) × 103 M-1 and (9.41 ± 0.03) × 103 M-1, respectively. The stability constant for the complexes of FLT with 2-HP-β-CD was (1.06 ± 0.06) × 103 M-1. However, FLT was observed to form a weak complex with 2-HP-γ-CD. Molecular dynamic (MD) simulations were used to investigate the mechanism and mode of inclusion processes, and to monitor the atomic-level stability of these complexes. The analysis of MD trajectories demonstrated that all guests formed stable inclusion complexes with both hosts throughout the duration of the simulation time, confirming the experimental findings. However, the flexible Hydroxypropyl arms prevented the PAHs from being encapsulated within the cavity; however, a stable exclusion complex was observed. The main forces that influenced the complexation included van der Waals interactions, hydrophobic forces, and C-H⋯π interaction, which contribute to the stability of these complexes.

Global AI governance: barriers and pathways forward

Abstract Recent advances in artificial intelligence (AI), combined with a proliferation in use, have led to a newfound emphasis on strengthening the global governance of AI. In this article, we assess the prospects for stronger global AI governance and consider potential pathways forward. We map the nascent landscape of international regimes focused on AI governance and conclude that a governance deficit remains due to the inadequacy of existing initiatives, gaps in the landscape and difficulties reaching agreement over more appropriate mechanisms. First-order cooperation problems stemming from interstate competition and second-order cooperation problems from dysfunctional international institutions problematize overcoming current deficiencies in global AI governance. In light of these cooperation problems, we evaluate two pathways for strengthening global AI governance: (a) developing new centralized international AI institution(s); and (b) strengthening coordination between, and capacities of, existing institutions. We argue that strengthening the existing weak ‘regime complex’ of international institutions is the more politically legitimate and viable path forward. Improving coordination between, and capacities of, existing international institutions governing AI would support inclusive and mutually reinforcing policy change that can mitigate a range of risks associated with these technologies. As first steps for strengthening the weak AI regime complex, we recommend that the OECD is foregrounded as a centre of expert AI knowledge so that it can facilitate peer pressure among states and harmonization of policies. We also encourage scrutiny of different nodes in the regime complex to ensure that they are fulfilling appropriate functions based on their democratic mandates.

Siderite with chelator as high-efficiency Fenton reagent to degrade naphthalene via ferrous liberation and carbon dioxide radical anion-mediated iron redox cycle

Siderite (FeCO3) has been verified to be an effective iron material in Fenton-like process, but large dose of FeCO3 and oxidants limits its application. Here, chelators were successfully used to enhance the degradation of naphthalene (NAP). When 1.0 mM of hydrogen peroxide (H2O2) and 1.0 g L−1 of FeCO3 were applied, in the presence of 0.2 mM oxalic acid (OA), 0.1 mM nitrilotriacetic acid (NTA), or 0.1 mM DL-tartaric acid (DL-TA), 99.3 %, 100 %, or 96.7 % of NAP was degraded within 24 h, respectively. The different roles of chelators were confirmed. For OA and DL-TA, due to weak complexation with iron ions, acid effect and generation of carbon dioxide radical anion (CO2−) contributed to high concentration of Fe2+, while for NTA, chelation and CO2− were two major factors. In addition, the excellent potential application of H2O2/FeCO3/chelator was determined because of (1) lower environmental risk of chemicals; (2) strong tolerance to water matrixes; (3) the excellent stability of FeCO3 confirmed by surface characterizations and cyclic experiment, as NAP was completely degraded after the 6th cycle. At last, H2O2/FeCO3/chelator had superiority over other reduced iron minerals due to lower running cost in lab study, better reusability, and environmental friendliness. Therefore, it is expected that H2O2/FeCO3/chelator technique can provide an effective alternative to Fenton-like process in remediation of NAP contaminated sites.

An Aptamer-Based Hydrogel Sensing Platform Enabling Low Micromolar Detection of Small Molecules Using Low Sample Volumes.

Poor fluorescence recovery at low analyte dosages and slow ligand binding kinetics are critical challenges currently limiting the use of aptamer-functionalized hydrogels for sensing small molecules. In this paper, we report an adenosine-responsive hydrogel sensor that integrates FRET-signaling aptamer switches into in situ-gelling thin-film hydrogels. The hydrogel sensor is able to entrap a high proportion of the sensing probes (>70% following vigorous washing), delay nucleolytic degradation, stabilize weak aptamer complexes to improve hybridization affinity and suppress fluorescence background, and provide high sensitivity in biological fluids (i.e., undiluted human serum). Furthermore, the developed hydrogel sensors were able to achieve low limits of detection (5.3 μM in buffer and 8.8 μM in serum) within 4 min of exposure to the sample, with signal generation requiring only 20 μL/well of analyte sample. The physical nature of the aptamer encapsulation allows this approach to accommodate virtually any small-molecule aptamer, avoiding the need for covalent anchoring and the complex modification of nucleic acid sequences typically required for effective aptamer-based molecular recognition.

Recent Progress on Cathode Materials for Rechargeable Zinc Ion Batteries

Due to their low cost, high capacity, mild assembly and testing conditions, as well as environmentally friendly characteristics, rechargeable zinc ion batteries (RZIBs) have attracted more and more attention. RZIBs have a broad development prospect and may partly replace the traditional batteries in the near future. Tremendous efforts have been devoted to developing various of high‐efficient cathode materials for improving comprehensive performances of RZIBs. However, many problems such as poor electron/ion conductivity, weak structural stability and complex energy storage mechanisms still exist in current cathode materials which hinder the practical application of RZIBs. This paper presents a timely review on recent progresses and challenges in cathode materials for rechargeable zinc ion batteries (RZIBs). Various types of reported cathode materials for RZIBs are summarized, their electrochemical performances were compared and their probable working mechanisms are investigated with the association of computational chemistry. Moreover, the existing problems and expected development directions of these materials were further discussed.

Sequential Infiltration Synthesis of Silicon Dioxide in Polymers with Ester Groups-Insight from In Situ Infrared Spectroscopy.

New strategies to synthesize nanometer-scale silicon dioxide (SiO2) patterns have drawn much attention in applications such as microelectronic and optoelectronic devices, membranes, and sensors, as we are approaching device dimensions shrinking below 10 nm. In this regard, sequential infiltration synthesis (SIS), a two-step gas-phase molecular assembly process that enables localized inorganic material growth in the targeted reactive domains of polymers, is an attractive process. In this work, we performed in situ Fourier transform infrared spectroscopy (FTIR) measurements during SiO2 SIS to investigate the reaction mechanism of trimethylaluminum (TMA) and tri(tert-pentoxy) silanol (TPS) precursors with polymers having ester functional groups (poly(methyl methacrylate) (PMMA), poly(ethyl methacrylate) (PEMA), polycaprolactone (PCL), and poly(t-butyl methacrylate) (PBMA)), for the purpose of growing patterned nanomaterials. The FTIR results show that for PMMA and PEMA, a lower percentage of functional groups participated in the reactions and formed weak and unstable complexes. In contrast, almost all functional groups in PCL and PBMA participated in the reactions and showed stable and irreversible interactions with TMA. We discovered that the amount of SiO2 formed is not directly correlated with the number of interacting functional groups. These insights into the SiO2 SIS mechanism will enable nanopatterning of SiO2 for low-dimensional applications.

Structural and mechanistic basis of the central energy-converting methyltransferase complex of methanogenesis

Methanogenic archaea inhabiting anaerobic environments play a crucial role in the global biogeochemical material cycle. The most universal electrogenic reaction of their methane-producing energy metabolism is catalyzed by N 5-methyl-tetrahydromethanopterin: coenzyme M methyltransferase (MtrABCDEFGH), which couples the vectorial Na+ transport with a methyl transfer between the one-carbon carriers tetrahydromethanopterin and coenzyme M via a vitamin B12 derivative (cobamide) as prosthetic group. We present the 2.08 Å cryo-EM structure of Mtr(ABCDEFG)3 composed of the central Mtr(ABFG)3 stalk symmetrically flanked by three membrane-spanning MtrCDE globes. Tetraether glycolipids visible in the map fill gaps inside the multisubunit complex. Putative coenzyme M and Na+ were identified inside or in a side-pocket of a cytoplasmic cavity formed within MtrCDE. Its bottom marks the gate of the transmembrane pore occluded in the cryo-EM map. By integrating Alphafold2 information, functionally competent MtrA-MtrH and MtrA-MtrCDE subcomplexes could be modeled and thus the methyl-tetrahydromethanopterin demethylation and coenzyme M methylation half-reactions structurally described. Methyl-transfer-driven Na+ transport is proposed to be based on a strong and weak complex between MtrCDE and MtrA carrying vitamin B12, the latter being placed at the entrance of the cytoplasmic MtrCDE cavity. Hypothetically, strongly attached methyl-cob(III)amide (His-on) carrying MtrA induces an inward-facing conformation, Na+ flux into the membrane protein center and finally coenzyme M methylation while the generated loosely attached (or detached) MtrA carrying cob(I)amide (His-off) induces an outward-facing conformation and an extracellular Na+ outflux. Methyl-cob(III)amide (His-on) is regenerated in the distant active site of the methyl-tetrahydromethanopterin binding MtrH implicating a large-scale shuttling movement of the vitamin B12-carrying domain.