-
Biochimica Et Biophysica Acta.... Feb 2022Phenylthiosemicarbazones (PTSCs) are proton-coupled anion transporters with pH-switchable behaviour known to be regulated by an imine protonation equilibrium....
Phenylthiosemicarbazones (PTSCs) are proton-coupled anion transporters with pH-switchable behaviour known to be regulated by an imine protonation equilibrium. Previously, chloride/nitrate exchange by PTSCs was found to be inactive at pH 7.2 due to locking of the thiourea anion binding site by an intramolecular hydrogen bond, and switched ON upon imine protonation at pH 4.5. The rate-determining process of the pH switch, however, was not examined. We here develop a new series of PTSCs and demonstrate their conformational behaviour by X-ray crystallographic analysis and pH-switchable anion transport properties by liposomal assays. We report the surprising finding that the protonated PTSCs are extremely selective for halides over oxyanions in membrane transport. Owing to the high chloride over nitrate selectivity, the pH-dependent chloride/nitrate exchange of PTSCs originates from the rate-limiting nitrate transport process being inhibited at neutral pH.
Topics: Anions; Chlorides; Crystallography, X-Ray; Hydrogen-Ion Concentration; Ion Transport; Kinetics; Nitrates; Protons; Thiosemicarbazones
PubMed: 34861222
DOI: 10.1016/j.bbamem.2021.183828 -
ChemSusChem Jun 2023Electrochemical CO reduction reaction (CO RR) is crucial to addressing environmental crises and producing chemicals. Proton activation and transfer are essential in CO...
Electrochemical CO reduction reaction (CO RR) is crucial to addressing environmental crises and producing chemicals. Proton activation and transfer are essential in CO RR. To date, few research reviews have focused on this process and its effect on catalytic performance. Recent studies have demonstrated ways to improve CO RR by regulating proton transfer dynamics. This Concept highlights the use of regulating proton transfer dynamics to enhance CO RR for the target product and discusses modulation strategies for proton transfer dynamics and operative mechanisms in typical systems, including single-atom catalysts, molecular catalysts, metal heterointerfaces, and organic-ligand modified metal catalysts. Characterization methods for proton transfer dynamics during CO RR are also discussed, providing powerful tools for the hydrogen-involving electrochemical study. This Concept offers new insights into the CO RR mechanism and guides the design of efficient CO RR systems.
Topics: Protons; Carbon Dioxide; Hydrogen; Catalysis
PubMed: 36820747
DOI: 10.1002/cssc.202202251 -
ELife Dec 2021Anion channelrhodopsin from (ACR1) has Asp234 (3.2 Å) and Glu68 (5.3 Å) near the protonated Schiff base. Here, we investigate mutant ACR1s (e.g., E68Q/D234N)...
Anion channelrhodopsin from (ACR1) has Asp234 (3.2 Å) and Glu68 (5.3 Å) near the protonated Schiff base. Here, we investigate mutant ACR1s (e.g., E68Q/D234N) expressed in HEK293 cells. The influence of the acidic residues on the absorption wavelengths was also analyzed using a quantum mechanical/molecular mechanical approach. The calculated protonation pattern indicates that Asp234 is deprotonated and Glu68 is protonated in the original crystal structures. The D234E mutation and the E68Q/D234N mutation shorten and lengthen the measured and calculated absorption wavelengths, respectively, which suggests that Asp234 is deprotonated in the wild-type ACR1. Molecular dynamics simulations show that upon mutation of deprotonated Asp234 to asparagine, deprotonated Glu68 reorients toward the Schiff base and the calculated absorption wavelength remains unchanged. The formation of the proton transfer pathway via Asp234 toward Glu68 and the disconnection of the anion conducting channel are likely a basis of the gating mechanism.
Topics: Anions; Biological Transport; Channelrhodopsins; Cryptophyta; HEK293 Cells; Humans; Mutation; Protons
PubMed: 34930528
DOI: 10.7554/eLife.72264 -
Chemphyschem : a European Journal of... Jan 2023The photodynamics of protonated tryptophan and its mono hydrated complex TrpH -H O has been revisited. A combination of steady-state IR and UV cryogenic ion...
The photodynamics of protonated tryptophan and its mono hydrated complex TrpH -H O has been revisited. A combination of steady-state IR and UV cryogenic ion spectroscopies with picosecond pump-probe photodissociation experiments sheds new lights on the deactivation processes of TrpH and conformer-selected TrpH -H O complex, supported by quantum chemistry calculations at the DFT and coupled-cluster levels for the ground and excited states, respectively. TrpH excited at the band origin exhibits a transient of less than 100 ps, assigned to the lifetime of the excited state proton transfer (ESPT) structure. The two experimentally observed conformers of TrpH -H O have been assigned. A striking result arises from the conformer-selective photodynamics of TrpH -H O, in which a single water molecule inserted in between the ammonium and the indole ring hinders the barrierless ESPT reaction responsible for the ultra-fast deactivation process observed in the other conformer and in bare TrpH .
Topics: Protons; Tryptophan; Water
PubMed: 36177693
DOI: 10.1002/cphc.202200561 -
Chemistry, An Asian Journal Oct 2023Red fluorescent proteins (RFPs) represent an increasingly popular class of genetically encodable bioprobes and biomarkers that can advance next-generation breakthroughs... (Review)
Review
Red fluorescent proteins (RFPs) represent an increasingly popular class of genetically encodable bioprobes and biomarkers that can advance next-generation breakthroughs across the imaging and life sciences. Since the rational design of RFPs with improved functions or enhanced versatility requires a mechanistic understanding of their working mechanisms, while fluorescence is intrinsically an ultrafast event, a suitable toolset involving steady-state and time-resolved spectroscopic techniques has become powerful in delineating key structural features and dynamic steps which govern irreversible photoconverting or reversible photoswitching RFPs, and large Stokes shift (LSS)RFPs. The pertinent cis-trans isomerization and protonation state change of RFP chromophores in their local environments, involving key residues in protein matrices, lead to rich and complicated spectral features across multiple timescales. In particular, ultrafast excited-state proton transfer in various LSSRFPs showcases the resolving power of wavelength-tunable femtosecond stimulated Raman spectroscopy (FSRS) in mapping a photocycle with crucial knowledge about the red-emitting species. Moreover, recent progress in noncanonical RFPs with a site-specifically modified chromophore provides an appealing route for efficient engineering of redder and brighter RFPs, highly desirable for bioimaging. Such an effective feedback loop involving physical chemists, protein engineers, and biomedical microscopists will enable future successes to expand fundamental knowledge and improve human health.
Topics: Humans; Luminescent Proteins; Spectrum Analysis, Raman; Protons
PubMed: 37682793
DOI: 10.1002/asia.202300668 -
Inorganic Chemistry Sep 2023Nitrogenase is a fascinating enzyme in biology that reduces dinitrogen from air to ammonia through stepwise reduction and protonation. Despite it being studied in detail...
Nitrogenase is a fascinating enzyme in biology that reduces dinitrogen from air to ammonia through stepwise reduction and protonation. Despite it being studied in detail by experimental and computational groups, there are still many unknown factors in the catalytic cycle of nitrogenase, especially related to the addition of protons and electrons and their order. A recent biomimetic study characterized a potential dinitrogen-bridged diiron cluster as a synthetic model of nitrogenase. Using strong acid and reductants, the dinitrogen was converted into ammonia molecules, but details of the mechanism remains unknown. In particular, it was unclear from the experimental studies whether the proton and electron transfer steps are sequential or alternating. Moreover, the work failed to establish what the function of the diiron core is and whether it split into mononuclear iron fragments during the reaction. To understand the structure and reactivity of the biomimetic dinitrogen-bridged diiron complex [(PFeH)(μ-N)] with triphenylphosphine ligands, we performed a density functional theory study. Our computational methods were validated against experimental crystal structure coordinates, Mössbauer parameters, and vibrational frequencies and show excellent agreement. Subsequently, we investigated the alternating and consecutive addition of electrons and protons to the system. The calculations identify a number of possible reaction channels, namely, same-site protonation, alternating protonation, and complex dissociation into mononuclear iron centers. The calculations show that the overall mechanism is not a pure sequential set of electron and proton transfers but a mixture of alternating and consecutive steps. In particular, the first reaction steps will start with double proton transfer followed by an electron transfer, while thereafter, there is another proton transfer and a second electron transfer to give a complex whereby ammonia can split off with a low energetic barrier. The second channel starts with alternating protonation of the two nitrogen atoms, whereafter the initial double proton transfer, electrons and protons are added sequentially to form a hydrazine-bound complex. The latter split off ammonia spontaneously after further protonation. The various reaction channels are analyzed with valence bond and orbital diagrams. We anticipate the nitrogenase enzyme to operate with mixed alternating and consecutive protonation and electron transfer steps.
Topics: Ammonia; Protons; Iron; Nitrogen; Nitrogenase
PubMed: 37650683
DOI: 10.1021/acs.inorgchem.3c02089 -
Advances in Protein Chemistry and... 2022Membrane transporters that use proton binding and proton transfer for function couple local protonation change with changes in protein conformation and water dynamics....
Membrane transporters that use proton binding and proton transfer for function couple local protonation change with changes in protein conformation and water dynamics. Changes of protein conformation might be required to allow transient formation of hydrogen-bond networks that bridge proton donor and acceptor pairs separated by long distances. Inter-helical hydrogen-bond networks adjust rapidly to protonation change, and ensure rapid response of the protein structure and dynamics. Membrane transporters with known three-dimensional structures and proton-binding groups inform on general principles of protonation-coupled protein conformational dynamics. Inter-helical hydrogen bond motifs between proton-binding carboxylate groups and a polar sidechain are observed in unrelated membrane transporters, suggesting common principles of coupling protonation change with protein conformational dynamics.
Topics: Hydrogen Bonding; Membrane Transport Proteins; Molecular Dynamics Simulation; Protein Conformation; Protons; Water
PubMed: 35034719
DOI: 10.1016/bs.apcsb.2021.09.002 -
Chemistry (Weinheim An Der Bergstrasse,... Oct 2021The kinetic isotope effect (KIE) is key to understanding reaction mechanisms in many areas of chemistry and chemical biology, including organometallic chemistry. This... (Review)
Review
The kinetic isotope effect (KIE) is key to understanding reaction mechanisms in many areas of chemistry and chemical biology, including organometallic chemistry. This ratio of rate constants, k /k , typically falls between 1-7. However, KIEs up to 105 have been reported, and can even be so large that reactivity with deuterium is unobserved. We collect here examples of large KIEs across organometallic chemistry, in catalytic and stoichiometric reactions, along with their mechanistic interpretations. Large KIEs occur in proton transfer reactions such as protonation of organometallic complexes and clusters, protonolysis of metal-carbon bonds, and dihydrogen reactivity. C-H activation reactions with large KIEs occur with late and early transition metals, photogenerated intermediates, and abstraction by metal-oxo complexes. We categorize the mechanistic interpretations of large KIEs into the following three types: (a) proton tunneling, (b) compound effects from multiple steps, and (c) semi-classical effects on a single step. This comprehensive collection of large KIEs in organometallics provides context for future mechanistic interpretation.
Topics: Carbon; Catalysis; Isotopes; Kinetics; Protons
PubMed: 34347912
DOI: 10.1002/chem.202102189 -
The Journal of Physical Chemistry. B Apr 2022Proteins are polyelectrolytes with acidic and basic amino acids Asp, Glu, Arg, Lys, and His, making up ≈25% of the residues. The protonation state of residues,...
Proteins are polyelectrolytes with acidic and basic amino acids Asp, Glu, Arg, Lys, and His, making up ≈25% of the residues. The protonation state of residues, cofactors, and ligands defines a "protonation microstate". In an ensemble of proteins some residues will be ionized and others neutral, leading to a mixture of protonation microstates rather than in a single one as is often assumed. The microstate distribution changes with pH. The protein environment also modifies residue proton affinity so microstate distributions change in different reaction intermediates or as ligands are bound. Particular protonation microstates may be required for function, while others exist simply because there are many states with similar energy. Here, the protonation microstates generated in Monte Carlo sampling in MCCE are characterized in HEW lysozyme as a function of pH and bacterial photosynthetic reaction centers (RCs) in different reaction intermediates. The lowest energy and highest probability microstates are compared. The Δ, Δ, and Δ between the four protonation states of Glu35 and Asp52 in lysozyme are shown to be calculated with reasonable precision. At pH 7 the lysozyme charge ranges from 6 to 10, with 24 accepted protonation microstates, while RCs have ≈50,000. A weighted Pearson correlation analysis shows coupling between residue protonation states in RCs and how they change when the quinone in the Q site is reduced. Protonation microstates can be used to define input MD parameters and provide insight into the motion of protons coupled to reactions.
Topics: Electron Transport; Hydrogen-Ion Concentration; Ligands; Monte Carlo Method; Muramidase; Photosynthetic Reaction Center Complex Proteins; Protons; Rhodobacter sphaeroides
PubMed: 35344367
DOI: 10.1021/acs.jpcb.2c00139 -
Journal of the American Chemical Society Mar 2022Proton transfer is ubiquitous in many fundamental chemical and biological processes, and the ability to modulate and control the proton transfer rate would have a major...
Proton transfer is ubiquitous in many fundamental chemical and biological processes, and the ability to modulate and control the proton transfer rate would have a major impact on numerous quantum technological advances. One possibility to modulate the reaction rate of proton transfer processes is given by exploiting the strong light-matter coupling of chemical systems inside optical or nanoplasmonic cavities. In this work, we investigate the proton transfer reactions in the prototype malonaldehyde and -3-amino-propenal (aminopropenal) molecules using different quantum electrodynamics methods, in particular, quantum electrodynamics coupled cluster theory and quantum electrodynamical density functional theory. Depending on the cavity mode polarization direction, we show that the optical cavity can increase the reaction energy barrier by 10-20% or decrease the reaction barrier by ∼5%. By using first-principles methods, this work establishes strong light-matter coupling as a viable and practical route to alter and catalyze proton transfer reactions.
Topics: Catalysis; Protons; Quantum Theory
PubMed: 35271261
DOI: 10.1021/jacs.1c13201