Electron Flow Characterization of Charge Transfer for Carbonic Acid to Strong Base Proton Transfer in Aqueous Solution.

Protonation of the strong base methylamine CH3NH2 by carbonic acid H2CO3 in aqueous solution, HOCOOH···NH2CH3 → HOCOO-···+HNH2CH3, has been previously studied ( J. Phys. Chem. B 2016, 109, 2271-2280; J. Phys. Chem. B 2016, 109, 2281-2290) via Car-Parinnello molecular dynamics. This proton transfer (PT) reaction within a hydrogen (H)-bonded complex was found to be barrierless and very rapid, with key reaction coordinates comprising the proton coordinate, the H-bond separation RON, and a solvent coordinate, reflecting the water solvent rearrangement involved in the neutral to ion pair conversion. In the present work, the reaction's charge flow aspects are analyzed in detail, especially a description via Mulliken charge transfer for PT (MCTPT). A natural bond orbital analysis and some extensions of them are employed for the complex's electronic structure during the reaction trajectories. Results demonstrate that consistent with the MCTPT picture, the charge transfer (CT) occurs from a methylamine base nonbonding orbital to a carbonic acid antibonding orbital. A complementary MCTPT reaction product perspective of CT from the antibonding orbital of the HN+ moiety to the nonbonding orbital of the oxygen in the H-bond complex is also presented. σOH and σHN+ bond order expressions show this CT to occur within the H-bond OHN triad, an aspect key for simultaneous bond-breaking and -forming in the PT reaction.

Trapped-ion toolkit for studies of quantum harmonic oscillators under extreme conditions.

Many phenomena described in relativistic quantum field theory are inaccessible to direct observations, but analogue processes studied under well-defined laboratory conditions can present an alternative perspective. Recently, we demonstrated an analogy of particle creation using an intrinsically robust motional mode of two trapped atomic ions. Here, we substantially extend our classical control techniques by implementing machine-learning strategies in our platform and, consequently, increase the accessible parameter regime. As a proof of methodology, we present experimental results of multiple quenches and parametric modulation of an unprotected motional mode of a single ion, demonstrating the increased level of real-time control. In combination with previous results, we enable future experiments that may yield entanglement generation using a process in analogy to Hawking radiation. This article is part of a discussion meeting issue 'The next generation of analogue gravity experiments'.

Valve-in-Valve for Degenerated Transcatheter Aortic Valve Replacement Versus Valve-in-Valve for Degenerated Surgical Aortic Bioprostheses: A 3-Center Comparison of Hemodynamic and 1-Year Outcome.

Background As transcatheter aortic valve replacement (TAVR) is expected to progress into younger patient populations, valve-in-TAVR (ViTAVR) may become a frequent consideration. Data on ViTAVR, however, are limited. This study investigated the outcome of ViTAVR in comparison to valve in surgical aortic valve replacement (ViSAVR), because ViSAVR is an established procedure for higher-risk patients requiring repeated aortic valve intervention. Methods and Results Clinical and procedural data of patients who underwent ViTAVR at 3 sites in the United States and Germany were retrospectively compared with data of patients who underwent ViSAVR at Cedars-Sinai Medical Center, according to Valve Academic Research Consortium-2 criteria. A total of 99 consecutive patients, 52.5% women, with a median Society of Thoracic Surgeons score of 7.2 were identified. Seventy-four patients (74.7%) underwent ViSAVR, and 25 patients (25.3%) underwent ViTAVR. Balloon-expandable devices were used in 72.7%. ViSAVR patients presented with smaller index devices (21.0 versus 26.0 mm median true internal diameter; P<0.001). Significantly better postprocedural hemodynamics (median prosthesis mean gradient, 12.5 [interquartile range, 8.8-16.2] versus 16.0 [interquartile range, 13.0-20.5] mm Hg; P=0.045) were observed for ViTAVR compared with the ViSAVR. Device success, however, was not different (79.2% and 66.2% for ViTAVR and ViSAVR, respectively; P=0.35), as were rates of permanent pacemaker implantation (16.7% versus 5.4%; P=0.1). One-year-mortality was 9.4% and 13.4% for ViTAVR and ViSAVR, respectively (log-rank P=0.38). Conclusions Compared with ViSAVR, ViTAVR provides acceptable outcomes, with slightly better hemodynamics, similar device success rates, and similar 1-year mortality.

Floquet-Engineered Vibrational Dynamics in a Two-Dimensional Array of Trapped Ions.

We demonstrate Floquet engineering in a basic yet scalable 2D architecture of individually trapped and controlled ions. Local parametric modulations of detuned trapping potentials steer the strength of long-range interion couplings and the related Peierls phase of the motional state. In our proof of principle, we initialize large coherent states and tune modulation parameters to control trajectories, directions, and interferences of the phonon flow. Our findings open a new pathway for future Floquet-based trapped-ion quantum simulators targeting correlated topological phenomena and dynamical gauge fields.

Phonon Pair Creation by Inflating Quantum Fluctuations in an Ion Trap.

Quantum theory predicts intriguing dynamics during drastic changes of external conditions. We switch the trapping field of two ions sufficiently fast to tear apart quantum fluctuations, i.e., create pairs of phonons and, thereby, squeeze the ions' motional state. This process can be interpreted as an experimental analog to cosmological particle creation and is accompanied by the formation of spatial entanglement. Hence, our platform allows one to study the causal connections of squeezing, pair creation, and entanglement and might permit one to cross-fertilize between concepts in cosmology and applications of quantum information processing.

Interference in a Prototype of a Two-Dimensional Ion Trap Array Quantum Simulator.

Trapped ions are a promising platform for envisioned quantum simulators, with outstanding results in one-dimensional ion crystals. However, theory requires not only interactions at long range, but also higher dimensionality. We operate a basic triangular array of three individually trapped ions based on scalable microfabrication technology. We demonstrate coherent coupling, tunable in real time and enabling interference in 2D, an essential building block for a reconfigurable quantum simulator. Mitigating motional heating will permit accessing the quantum regime and 2D experimental quantum simulations.

Intact carbonic acid is a viable protonating agent for biological bases.

Carbonic acid H2CO3 (CA) is a key constituent of the universal CA/bicarbonate/CO2 buffer maintaining the pH of both blood and the oceans. Here we demonstrate the ability of intact CA to quantitatively protonate bases with biologically-relevant pKas and argue that CA has a previously unappreciated function as a major source of protons in blood plasma. We determine with high precision the temperature dependence of pKa(CA), pKa(T) = -373.604 + 16,500/T + 56.478 ln T. At physiological-like conditions pKa(CA) = 3.45 (I = 0.15 M, 37 °C), making CA stronger than lactic acid. We further demonstrate experimentally that CA decomposition to H2O and CO2 does not impair its ability to act as an ordinary carboxylic acid and to efficiently protonate physiological-like bases. The consequences of this conclusion are far reaching for human physiology and marine biology. While CA is somewhat less reactive than (H+)aq, it is more than 1 order of magnitude more abundant than (H+)aq in the blood plasma and in the oceans. In particular, CA is about 70× more abundant than (H+)aq in the blood plasma, where we argue that its overall protonation efficiency is 10 to 20× greater than that of (H+)aq, often considered to be the major protonating agent there. CA should thus function as a major source for fast in vivo acid-base reactivity in the blood plasma, possibly penetrating intact into membranes and significantly helping to compensate for (H+)aq's kinetic deficiency in sustaining the large proton fluxes that are vital for metabolic processes and rapid enzymatic reactions.

Hybrid setup for stable magnetic fields enabling robust quantum control.

Well controlled and highly stable magnetic fields are desired for a wide range of applications in physical research, including quantum metrology, sensing, information processing, and simulation. Here we introduce a low-cost hybrid assembly of rare-earth magnets and magnetic field coils to generate a field strength of [Formula: see text]10.9 mT with a calculated spatial variation of less than 10-6 within a diameter of spherical volume of 150 µm. We characterise its tuneability and stability performance using a single Mg+ atom confined in a radio-frequency surface-electrode trap under ultra-high vacuum conditions. The strength of the field can be tuned with a relative precision of ≤2 × 10-5 and we find a passive temporal stability of our setup of better than 1.0 × 10-4 over the course of one hour. Slow drifts on time scales of a few minutes are actively stabilised by adjusting electric currents in the magnetic field coils. In this way, we observe coherence times of electronic superposition states of greater than six seconds using a first-order field insensitive (clock) transition. In a first application, we demonstrate sensing of magnetic fields with amplitudes of ≥0.2 µT oscillating at [Formula: see text]2π × 60 MHz. Our approach can be implemented in compact and robust applications with strict power and load requirements.

Reaction Mechanism for Direct Proton Transfer from Carbonic Acid to a Strong Base in Aqueous Solution I: Acid and Base Coordinate and Charge Dynamics.

Protonation by carbonic acid H2CO3 of the strong base methylamine CH3NH2 in a neutral contact pair in aqueous solution is followed via Car-Parrinello molecular dynamics simulations. Proton transfer (PT) occurs to form an aqueous solvent-stabilized contact ion pair within 100 fs, a fast time scale associated with the compression of the acid-base hydrogen-bond (H-bond), a key reaction coordinate. This rapid barrierless PT is consistent with the carbonic acid-protonated base pKa difference that considerably favors the PT, and supports the view of intact carbonic acid as potentially important proton donor in assorted biological and environmental contexts. The charge redistribution within the H-bonded complex during PT supports a Mulliken picture of charge transfer from the nitrogen base to carbonic acid without altering the transferring hydrogen's charge from approximately midway between that of a hydrogen atom and that of a proton.

Reaction Mechanism for Direct Proton Transfer from Carbonic Acid to a Strong Base in Aqueous Solution II: Solvent Coordinate-Dependent Reaction Path.

The protonation of methylamine base CH3NH2 by carbonic acid H2CO3 within a hydrogen (H)-bonded complex in aqueous solution was studied via Car-Parrinello dynamics in the preceding paper (Daschakraborty, S.; Kiefer, P. M.; Miller, Y.; Motro, Y.; Pines, D.; Pines, E.; Hynes, J. T. J. Phys. Chem. B 2016, DOI: 10.1021/acs.jpcb.5b12742). Here some important further details of the reaction path are presented, with specific emphasis on the water solvent's role. The overall reaction is barrierless and very rapid, on an ∼100 fs time scale, with the proton transfer (PT) event itself being very sudden (<10 fs). This transfer is preceded by the acid-base H-bond's compression, while the water solvent changes little until the actual PT occurrence; this results from the very strong driving force for the reaction, as indicated by the very favorable acid-protonated base ΔpKa difference. Further solvent rearrangement follows immediately the sudden PT's production of an incipient contact ion pair, stabilizing it by establishment of equilibrium solvation. The solvent water's short time scale ∼120 fs response to the incipient ion pair formation is primarily associated with librational modes and H-bond compression of water molecules around the carboxylate anion and the protonated base. This is consistent with this stabilization involving significant increase in H-bonding of hydration shell waters to the negatively charged carboxylate group oxygens' (especially the former H2CO3 donor oxygen) and the nitrogen of the positively charged protonated base's NH3(+).

How Acidic Is Carbonic Acid?

Carbonic, lactic, and pyruvic acids have been generated in aqueous solution by the transient protonation of their corresponding conjugate bases by a tailor-made photoacid, the 6-hydroxy-1-sulfonate pyrene sodium salt molecule. A particular goal is to establish the pK(a) of carbonic acid H2CO3. The on-contact proton transfer (PT) reaction rate from the optically excited photoacid to the carboxylic bases was derived, with unprecedented precision, from time-correlated single-photon-counting measurements of the fluorescence lifetime of the photoacid in the presence of the proton acceptors. The time-dependent diffusion-assisted PT rate was analyzed using the Szabo-Collins-Kimball equation with a radiation boundary condition. The on-contact PT rates were found to follow the acidity order of the carboxylic acids: the stronger was the acid, the slower was the PT reaction to its conjugate base. The pK(a) of carbonic acid was found to be 3.49 ± 0.05 using both the Marcus and Kiefer-Hynes free energy correlations. This establishes H2CO3 as being 0.37 pK(a) units stronger and about 1 pK(a) unit weaker, respectively, than the physiologically important lactic and pyruvic acids. The considerable acid strength of intact carbonic acid indicates that it is an important protonation agent under physiological conditions.

Effect of Solvent Dielectric Constant and Acidity on the OH Vibration Frequency in Hydrogen-Bonded Complexes of Fluorinated Ethanols.

Infrared spectroscopy measurements were used to characterize the OH stretching vibrations in a series of similarly structured fluoroethanols, RCH2OH (R = CH3, CH2F, CHF2, CF3), a series which exhibits a systematic increase in the molecule acidity with increasing number of F atoms. This study, which expands our earlier efforts, was carried out in non-hydrogen-bonding solvents comprising molecules with and without a permanent dipole moment, with the former solvents being classified as polar solvents and the latter designated as nonpolar. The hydrogen bond interaction in donor-acceptor complexes formed in solution between the fluorinated ethanol H-donors and the H-acceptor base DMSO was investigated in relation to the solvent dielectric and to the differences ΔPA of the gas phase proton affinities (PAs) of the conjugate base of the fluorinated alcohols and DMSO. We have observed that νOH decreases as the acidity of the alcohol increases (ΔPA decreases) and that νOH varies inversely with ε, exhibiting different slopes for nonpolar and polar solvents. These 1/ε slopes tend to vary linearly with ΔPA, increasing with increasing acidity. These experimental findings, including the ΔPA trends, are described with our recently published two-state Valence Bond-based theory for acid-base H-bonded complexes. Lastly, the correlation of the alcohol's conjugate base PAs with Taft σ* values of the fluorinated ethyl groups CH(n)F(3-n)CH2- provides a connection of the inductive effects for these groups with the acidity parameter ΔPA associated with the H-bonded complexes.

Solvent-induced O-H vibration red-shifts of oxygen-acids in hydrogen-bonded O-H···base complexes.

Infrared spectroscopy has been used to characterize the solvent effect on the OH stretching vibrations νOH of phenol, 1-naphthol, 2-naphthol, 1-hydroxypyrene, and ethanol. We distinguish the dielectric (nonspecific) effect of the solvent on ΔνOH, the observed red-shifts in νOH, from the much larger red-shift caused by direct hydrogen (H)-bonding interactions with the solvents. To isolate the solvent dielectric constant ε effect on νOH, the OH oscillator was also studied when it is already H-bonded with an invariant oxygen base, dimethyl sulfoxide. We find that ΔνOH depends importantly on ΔPA, the difference between the proton affinities of the conjugate base of the proton donor and the proton acceptor. For a given H-bonded complex, νOH tends to vary inversely with ε, exhibiting different slopes for polar and nonpolar solvents, i.e., solvents comprising molecules with and without a permanent dipole moment, respectively. We use a two-state valence-bond-based theory to analyze our experimental data. This demonstrates that the OH oscillator acquires a more ionic-like character in the vibrational excited state, i.e., charge transfer; this results in a stronger H-bond in a more anharmonic potential for the OH vibration. The theory distinguishes between nonpolar and polar solvents and successfully accounts for the observed 1/ε and ΔPA variations.

Solvent-induced red-shifts for the proton stretch vibrational frequency in a hydrogen-bonded complex. 1. A valence bond-based theoretical approach.

A theory is presented for the proton stretch vibrational frequency νAH for hydrogen (H-) bonded complexes of the acid dissociation type, that is, AH···B ⇔ A(-)···HB(+)(but without complete proton transfer), in both polar and nonpolar solvents, with special attention given to the variation of νAH with the solvent's dielectric constant ε. The theory involves a valence bond (VB) model for the complex's electronic structure, quantization of the complex's proton and H-bond motions, and a solvent coordinate accounting for nonequilibrium solvation. A general prediction is that νAH decreases with increasing ε largely due to increased solvent stabilization of the ionic VB structure A(-)···HB(+) relative to the neutral VB structure AH···B. Theoretical νAH versus 1/ε slope expressions are derived; these differ for polar and nonpolar solvents and allow analysis of the solvent dependence of νAH. The theory predicts that both polar and nonpolar slopes are determined by (i) a structure factor reflecting the complex's size/geometry, (ii) the complex's dipole moment in the ground vibrational state, and (iii) the dipole moment change in the transition, which especially reflects charge transfer and the solution phase proton potential shapes. The experimental proton frequency solvent dependence for several OH···O H-bonded complexes is successfully accounted for and analyzed with the theory.

The reaction catalyzed by tetrachlorohydroquinone dehalogenase does not involve nucleophilic aromatic substitution.

Tetrachlorohydroquinone dehalogenase catalyzes the reductive dehalogenation of tetrachlorohydroquinone and trichlorohydroquinone during the biodegradation of the xenobiotic compound pentachlorophenol by Sphingobium chlorophenolicum. The mechanism of this transformation is of interest because it is unusual and difficult, and because aerobic microorganisms rarely catalyze reductive dehalogenation reactions. Tetrachlorohydroquinone dehalogenase is a member of the glutathione S-transferase superfamily. Many enzymes in this superfamily are capable of catalyzing nucleophilic aromatic substitution reactions. On the basis of this precedent, we have considered a mechanism for tetrachlorohydroquinone dehalogenase that involves a nucleophilic aromatic substitution reaction, either via an S(N)Ar mechanism or an S(RN)1-like mechanism, in the initial part of the reaction. Mechanistic studies were carried out with the wild type enzyme and with the C13S mutant enzyme, which catalyzes only the initial steps in the reaction. Three findings eliminate the possibility of a nucleophilic aromatic substitution reaction. First, the product of such a reaction, 2,3,5-trichloro-6-S-glutathionylhydroquinone, is not a kinetically competent intermediate. Second, the enzyme can carry out the reaction when the substrate is deprotonated at the active site. Nucleophilic aromatic substitution should not be possible when the substrate is negatively charged. Third, substantial normal solvent kinetic isotope effects on k(cat) and k(cat)/K(M,TriCHQ) are observed. Nonenzymatic and enzymatic nucleophilic S(N)Ar reactions typically show inverse solvent kinetic isotope effects.

Characterization of the initial steps in the reductive dehalogenation catalyzed by tetrachlorohydroquinone dehalogenase.

Tetrachlorohydroquinone dehalogenase catalyzes the reductive dehalogenation of tetrachlorohydroquinone and trichlorohydroquinone during the degradation of pentachlorophenol by Sphingbium chlorophenolicum. Remarkably, the same active site catalyzes the glutathione-dependent isomerization of a double bond in maleylacetone (an analogue of maleylacetoacetate and maleylpyruvate) [Anandarajah, K. et al. (2000) Biochemistry 39, 5303-5311]. The mechanism of the initial steps in the reaction has been probed using the C13S mutant enzyme, which catalyzes the reaction only to the point at which Cys13 is required. The reaction proceeds by a rapid equilibrium random sequential kinetic mechanism. Substrate analogues that lack a second hydroxyl group cannot be turned over to products, although they can bind to the active site. The rate of the reaction is strongly influenced by the number of electron-withdrawing substituents on the substrate. These findings are consistent with a mechanism that begins with ketonization of the deprotonated substrate to form 2,3,5,6-tetrachloro-4-hydroxycyclohexa-2,4-dienone, followed by 1,4-elimination of HCl to from trichlorobenzoquinone. Subsequently, trichlorobenzoquinone is attacked by glutathione to form a glutathione conjugate that, in the absence of Cys13, decomposes to a mixture of products, either at the active site or after release into solution. Possible similarities between this mechanism and the mechanism for isomerization of maleylacetoacetate and maleylpyruvate are discussed.