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The Journal of Physical Chemistry. B Apr 2021
Topics: Protons
PubMed: 33882678
DOI: 10.1021/acs.jpcb.1c01929 -
Physics in Medicine and Biology Feb 2022Proton beam therapy can potentially offer improved treatment for cancers of the head and neck and in paediatric patients. There has been a sharp uptake of proton beam...
Proton beam therapy can potentially offer improved treatment for cancers of the head and neck and in paediatric patients. There has been a sharp uptake of proton beam therapy in recent years as improved delivery techniques and patient benefits are observed. However, treatments are currently planned using conventional x-ray CT images due to the absence of devices able to perform high quality proton computed tomography (pCT) under realistic clinical conditions. A new plastic-scintillator-based range telescope concept, named ASTRA, is proposed here to measure the proton's energy loss in a pCT system. Simulations conducted using GEANT4 yield an expected energy resolution of 0.7%. If calorimetric information is used the energy resolution could be further improved to about 0.5%. In addition, the ability of ASTRA to track multiple protons simultaneously is presented. Due to its fast components, ASTRA is expected to reach unprecedented data collection rates, similar to 10protons/s. The performance of ASTRA has also been tested by simulating the imaging of phantoms. The results show excellent image contrast and relative stopping power reconstruction.
Topics: Child; Data Collection; Humans; Image Processing, Computer-Assisted; Monte Carlo Method; Phantoms, Imaging; Proton Therapy; Protons; Telescopes; Tomography, X-Ray Computed
PubMed: 35026744
DOI: 10.1088/1361-6560/ac4b39 -
Journal of the American Chemical Society May 2024We present a detailed study of the time-dependent photophysics and photochemistry of a known conformation of the two protonated pentapeptides Leu-enkephalin...
We present a detailed study of the time-dependent photophysics and photochemistry of a known conformation of the two protonated pentapeptides Leu-enkephalin (Tyrosine-Glycine-Glycine-Phenylalanine-Leucine, YGGFL) and its chromophore-swapped analogue FGGYL, carried out under cryo-cooled conditions in the gas phase. Using ultraviolet-infrared (UV-IR) double resonance, we record excited state IR spectra as a function of time delay between UV and IR pulses. We identify unique Tyr OH stretch transitions due to the S state and the vibrationally excited triplet state(s) formed by intersystem crossing, T(v). Photofragment mass spectra are recorded out of the S origin and following UV-IR double resonance. Several competing site-specific fragmentation pathways are discovered involving peptide backbone cleavage, Tyr side chain loss, and N-terminal NH loss mediated by electron transfer. In YGGFL, IR excitation in the S state promotes electron transfer (ET) from the aromatic ring to the N-terminal R-NH group leading to loss of neutral NH. This product channel is missing in FGGYL due to the larger distance for ET from Y(4) to NH. Selective loss of the Tyr side chain occurs out of an excited state process following UV excitation and is further enhanced by IR excitation in S and T(v) states of both YGGFL and FGGYL. Finally, IR excitation in the S or T(v) states fragments the peptide backbone exclusively at amide(4), producing the b cation. We postulate that this selective fragmentation results from intersystem crossing to produce vibrationally excited triplets with enough energy to launch the proton along a proton conduit present in the known starting structure.
Topics: Protons; Photochemical Processes; Spectrophotometry, Infrared; Peptides; Enkephalin, Leucine
PubMed: 38687970
DOI: 10.1021/jacs.4c01576 -
Water Research Feb 2023The surface reactivity of iron (hydr)oxides plays a crucial role in controlling their interfacial reactions, for which various surface complexation models have been...
The surface reactivity of iron (hydr)oxides plays a crucial role in controlling their interfacial reactions, for which various surface complexation models have been developed. The diversity of mineralogical properties of iron (hydr)oxides has resulted in a redundancy of model parameters, which hampers the modeling of iron (hydr)oxides in soils and sediments, where goethite, hematite and ferrihydrite dominate the iron (hydr)oxide mass fraction. To capture their combined surface reactivity, optimized generic protonation parameters of the Charge Distribution-Multisite Complexation (CD-MUSIC) extended-Stern-Gouy-Chapman (eSGC) model were derived by reanalyzing literature datasets and tested with some newly synthesized iron (hydr)oxides. It was observed that the proton and monovalent ion affinity constants of the different iron (hydr)oxides were located in a narrow range. For the singly- and triply-coordinated hydroxyl sites the obtained generic log(affinity constants) were 8.3 and 11.7 for the protonation reaction and -0.5 for the reaction with the monovalent background ions. Their combination with fixed site densities of singly-/triply-coordinated hydroxyl sites of 3.45/2.70, 5.00/2.50, and 5.80/1.40 sites/nm for goethite, hematite, and ferrihydrite, respectively, provided good results. The Stern layer capacitances of the inner and outer Stern layers were set equal and could be acquired by an empirical correlation with the sample specific surface area (SSA). The CD-MUSIC-eSGC model with the generic model parameters enables good quality predictions of the proton reactivity of iron (hydr)oxides in 1:1 electrolyte solutions regardless of the sample heterogeneity. The advantages of the generic CD-MUSIC-eSGC model are twofold: (1) protonation of iron (hydr)oxides can be described without making use of spectroscopic measurements and proton titrations, and (2) the model calculations are greatly simplified.
Topics: Iron; Oxides; Protons; Music; Adsorption; Ferric Compounds; Minerals
PubMed: 36628867
DOI: 10.1016/j.watres.2022.119534 -
Physical Chemistry Chemical Physics :... Sep 2019Rational modification of biomolecules especially DNA base pairs for the theoretical design of molecular magnets has attracted extensive interest. In this work, we report...
Rational modification of biomolecules especially DNA base pairs for the theoretical design of molecular magnets has attracted extensive interest. In this work, we report a modification strategy for adenine/thymine-based magnets through introducing a N,N-dioxidized pyrazine ring to either adenine or thymine to form ring-expanded bases (noA/noT) based on their experimentally synthesized derivatives. Further functionalization is conducted by double protonation and pairing with a normal complementary base (nohA-T/nohT-A), respectively. The diversity of protonation sites in noA generates totally six nohA-Ts, together with nohT-A forming seven two-step modified topic base pairs. DFT calculations are performed to characterize the magnetic properties and the diradical character, which indicate three diamagnetic (DM) nohA-Ts and three antiferromagnetic (AFM) nohA-Ts with extremely large magnetic coupling constants J ranging from -1279.7 to -2807.4 cm-1, while a relatively mild AFM nohT-A with a J of -194.6 cm-1. The electron separation effect induced by attraction of positive charges originating from protonation is proposed to explain the diradicalization, which is different from the traditional radical-coupler-radical coupling mode. In addition, atomic natural charges and spin densities, and H-bond and molecular orbital analyses are further discussed for verification and deep understanding of the observed unique phenomena. It should be noted that our designed seven topic base pairs have excellent characters including a good synthetic basis, a large scope of the |J| values, and the AFM-DM magnetic conversion or AFM strength modulation controlled by protonation/deprotonation, prototropic tautomerization, base pairing/dissociation, single proton transfer, and even the applied electric field. All these indicate the promising applications in the field of magnetic information storage or switch control. This work highlights the magnetic modification schemes and possible modulation methods of double positive charge doped DNA base pairs by utilizing their potential spin coupling modes.
Topics: Base Pairing; DNA; Magnetics; Protons; Pyrazines; Thymine
PubMed: 31482894
DOI: 10.1039/c9cp03234g -
Applied Radiation and Isotopes :... Oct 2022The theoretical model codes ALICE/ASH and TALYS-1.95(G) were used to make theoretical predictions of the production cross-sections of I, I, I, I, I, I, and I... (Review)
Review
The theoretical model codes ALICE/ASH and TALYS-1.95(G) were used to make theoretical predictions of the production cross-sections of I, I, I, I, I, I, and I radionuclides produced in the interaction of proton-projectile with Te-target at energies ≈ 5-100 MeV. The results were compared with the measured values in the literature and with TENDL-2019 evaluated data. The Pearson's correlation coefficient indicates a strong and positive correlation between the predicted and the previously measured production cross-sections for medically important I, I, I, and I radionuclides. Further, the results show that the TALYS-1.95(G) code predicts more successful outcomes than the ALICE/ASH code for I, I, I, and I radionuclides production, which have widespread medical applications, particularly for diagnostic and therapeutic purposes.
Topics: Protons
PubMed: 35803178
DOI: 10.1016/j.apradiso.2022.110351 -
Chemistry (Weinheim An Der Bergstrasse,... Mar 2022We have used combined quantum mechanical and molecular mechanical (QM/MM) calculations to study the reaction mechanism of nitrogenase, assuming that none of the sulfide...
We have used combined quantum mechanical and molecular mechanical (QM/MM) calculations to study the reaction mechanism of nitrogenase, assuming that none of the sulfide ligands dissociates. To avoid the problem that there is no consensus regarding the structure and protonation of the E state, we start from a state where N is bound to the cluster and is protonated to N H , after dissociation of H . We show that the reaction follows an alternating mechanism with HNNH (possibly protonated to HNNH ) and H NNH as intermediates and the two NH products dissociate at the E and E levels. For all intermediates, coordination to Fe6 is preferred, but for the E and E intermediates, binding to Fe2 is competitive. For the E , E and E intermediates we find that the substrate may abstract a proton from the hydroxy group of the homocitrate ligand of the FeMo cluster, thereby forming HNNH , H NNH and NH intermediates. This may explain why homocitrate is a mandatory component of nitrogenase. All steps in the suggested reaction mechanism are thermodynamically favourable compared to protonation of the nearby His-195 group and in all cases, protonation of the NE2 atom of the latter group is preferred.
Topics: Ligands; Molybdoferredoxin; Nitrogenase; Protons; Sulfides
PubMed: 35006641
DOI: 10.1002/chem.202103933 -
Journal of Chemical Theory and... Dec 2022Constant pH molecular dynamics (MD) simulations sample protonation states on the fly according to the conformational environment and user specified pH conditions;...
Constant pH molecular dynamics (MD) simulations sample protonation states on the fly according to the conformational environment and user specified pH conditions; however, the current accuracy is limited due to the use of implicit-solvent models or a hybrid solvent scheme. Here, we report the first GPU-accelerated implementation, parametrization, and validation of the all-atom continuous constant pH MD (CpHMD) method with particle-mesh Ewald (PME) electrostatics in the Amber22 engine. The titration parameters for Asp, Glu, His, Cys, and Lys were derived for the CHARMM c22 and Amber ff14sb and ff19sb force fields. We then evaluated the PME-CpHMD method using the asynchronous pH replica-exchange titration simulations with the c22 force field for six benchmark proteins, including BBL, hen egg white lysozyme (HEWL), staphylococcal nuclease (SNase), thioredoxin, ribonuclease A (RNaseA), and human muscle creatine kinase (HMCK). The root-mean-square deviation from the experimental p's of Asp, Glu, His, and Cys is 0.76 pH units, and the Pearson's correlation coefficient for the p shifts with respect to model values is 0.80. We demonstrated that a finite-size correction or much enlarged simulation box size can remove a systematic error of the calculated p's and improve agreement with experiment. Importantly, the simulations captured the relevant biology in several challenging cases, e.g., the titration order of the catalytic dyad Glu35/Asp52 in HEWL and the coupled residues Asp19/Asp21 in SNase, the large p upshift of the deeply buried catalytic Asp26 in thioredoxin, and the large p downshift of the deeply buried catalytic Cys283 in HMCK. We anticipate that PME-CpHMD will offer proper pH control to improve the accuracies of MD simulations and enable mechanistic studies of proton-coupled dynamical processes that are ubiquitous in biology but remain poorly understood due to the lack of experimental tools and limitation of current MD simulations.
Topics: Humans; Hydrogen-Ion Concentration; Molecular Dynamics Simulation; Protons; Static Electricity; Software; Proteins
PubMed: 36377980
DOI: 10.1021/acs.jctc.2c00586 -
International Journal of Molecular... Nov 2022Excited-State Intramolecular Photon Transfer (ESIPT) is known for the geometry-related phenolic and imine groups. The Schiff bases formed upon condensation of salicyl...
Excited-State Intramolecular Photon Transfer (ESIPT) is known for the geometry-related phenolic and imine groups. The Schiff bases formed upon condensation of salicyl aldehyde and glycine led to the formation of ESIPT models. A series of alkali metal salicyliden glycinates were analyzed by X-ray diffraction of their monocrystals and spectroscopy measurements. The X-ray analysis revealed varied hydration levels between the salts. They adapted trans geometry on the imine groups and mostly anticlinal conformation with the neighboring atoms, which is different from the other structurally-related compounds in literature. Fluorescence of these compounds was found for the crystalline forms only. Protonation of the imine nitrogen atom and further proton distribution was consistent with the ESIPT theory, which also explained the observed fluorescence with the highest Stokes shift of 10,181 cm and 10.1% of fluorescence quantum yield for the sodium salt.
Topics: Schiff Bases; Protons; Molecular Conformation; Photons; Chemical Phenomena; Imines
PubMed: 36499284
DOI: 10.3390/ijms232314955 -
Current Opinion in Structural Biology Oct 2020Proton transfer reactions are ubiquitous in biology, as they are involved in the functioning of numerous proteins. Studies of model proteins have revealed mechanisms by... (Review)
Review
Proton transfer reactions are ubiquitous in biology, as they are involved in the functioning of numerous proteins. Studies of model proteins have revealed mechanisms by which proteins use hydrogen-bond networks for proton transfers, and couple proton transfers with protein and water dynamics. In this review we focus on graph-based analyses of dynamic hydrogen-bond networks at membrane interfaces, protein H-bond networks for allosteric conformational coupling and pH sensitivity, and challenges in extrapolating from knowledge acquired from studies of model membrane proteins to computational studies of macro-molecular protein complexes that are part of cell signaling networks directly relevant to the development of new therapeutics.
Topics: Hydrogen Bonding; Membrane Proteins; Protons; Signal Transduction; Water
PubMed: 32683247
DOI: 10.1016/j.sbi.2020.06.006