Direct Probe of Vibrational Fingerprint and Combination Band Coupling.

Vibrational fingerprints and combination bands are a direct measure of couplings that control molecular properties. However, most combination bands possess small transition dipoles. Here we use multiple, ultrafast coherent infrared pulses to resolve vibrational coupling between CHCN fingerprint modes at 918 and 1039 cm and combination bands in the 2750-6100 cm region via doubly vibrationally enhanced (DOVE) coherent multidimensional spectroscopy (CMDS).

Characterization of the Oxazolone and Macrocyclic Motifs in the b ( = 2-5) Product Ions from Collision-Induced Dissociation of Protonated Oligoglycine Peptides with Isomer-Selective, Cryogenic Vibrational Spectroscopy.

Collision-induced dissociation (CID) of small, protonated peptides leads to the formation of b-type fragment ions that can occur with several structural motifs driven by different covalent intramolecular bonding arrangements. Here, we characterize the so-called "oxazolone" and "macrocycle" ion structures that occur upon CID of oligoglycine peptides (G) ions ( = 2-6). This is determined by acquiring the vibrational band patterns of the cryogenically cooled, D-tagged ions obtained using isomer-selective, two-color IR-IR photobleaching and analyzing them with predicted (DFT) harmonic spectra for the candidate structures.

A general expression for vibrational Hamiltonians expressed in oblique coordinates.

We examine the properties of oblique coordinates. The coordinates, introduced by Zúñiga et al. [J.

Investigating Intramolecular H Atom Transfer Dynamics in β-Diketones with Ultrafast Infrared Spectroscopies and Theoretical Modeling.

The vibrational signatures and ultrafast dynamics of the intramolecular H-bond in a series of β-diketones are investigated with 2D IR spectroscopy and computational modeling. The chosen β-diketones exhibit a range of H atom donor-acceptor distances and asymmetry along the H atom transfer coordinate that tunes the intramolecular H-bond strength. The species with the strongest H-bonds are calculated to have very soft H atom potentials, resulting in highly red-shifted OH stretch fundamental frequencies and dislocation of the H atom upon vibrational excitation.

TNF and type I IFN induction of the IRG1-itaconate pathway restricts replication within mouse macrophages.

The intracellular Gram-negative bacterium replicates within macrophages and causes a zoonotic disease known as Q fever. In murine macrophages, the cytokine tumor necrosis factor (TNF) is critical for restriction of intracellular replication. Here, we show that TNF collaborates with type I interferon (IFN) signaling for maximal control of .

High-Resolution Photoelectron Spectroscopy of Vibrationally Excited Vinoxide Anions.

High-resolution photoelectron spectra of vibrationally pre-excited vinoxide anions (CHCHO) are reported using the recently developed IR-cryo-SEVI technique. This method is combined with a newly developed implementation of vibrational perturbation theory that can readily identify relevant anharmonic couplings among nearly degenerate vibrational states. IR-cryo-SEVI spectra are obtained by resonant infrared excitation of vinoxide anions via the fundamental C-O (ν, 1566 cm) or isolated C-H (ν, 2540 cm) stretching vibrations prior to photodetachment.

A wave function correction-based approach to the identification of resonances for vibrational perturbation theory.

An approach for identifying resonances in vibrational perturbation theory calculations is introduced. This approach makes use of the corrections to the wave functions that are obtained from non-degenerate perturbation theory calculations to identify spaces of states that must be treated with degenerate perturbation theory. Pairs of states are considered to be in resonance if the magnitude of expansion coefficients in the corrections to the wave functions in the non-degenerate perturbation theory calculation is greater than a specified threshold, χ.

Exploring Expansions of the Potential and Dipole Surfaces Used for Vibrational Perturbation Theory.

A scheme for evaluating expansions of the potential and dipole moment surfaces for vibrational perturbation theory is described. The approach is based on numerical differentiation of the Hessian in the coordinates of interest. It is shown that performing these calculations in internal coordinates generates expansions that are transferable among isotopologues of the molecule of interest.

Fast Near Potential Energy Surfaces Using Machine Learning.

A machine-learning based approach for evaluating potential energies for quantum mechanical studies of properties of the ground and excited vibrational states of small molecules is developed. This approach uses the molecular-orbital-based machine learning (MOB-ML) method to generate electronic energies with the accuracy of CCSD(T) calculations at the same cost as a Hartree-Fock calculation. To further reduce the computational cost of the potential energy evaluations without sacrificing the CCSD(T) level accuracy, GPU-accelerated Neural Network Potential Energy Surfaces (NN-PES) are trained to geometries and energies that are collected from small-scale Diffusion Monte Carlo (DMC) simulations, which are run using energies evaluated using the MOB-ML model.

Electronic and mechanical anharmonicities in the vibrational spectra of the H-bonded, cryogenically cooled X · HOCl (X=Cl, Br, I) complexes: Characterization of the strong anionic H-bond to an acidic OH group.

We report vibrational spectra of the H-tagged, cryogenically cooled X · HOCl (X = Cl, Br, and I) ion-molecule complexes and analyze the resulting band patterns with electronic structure calculations and an anharmonic theoretical treatment of nuclear motions on extended potential energy surfaces. The complexes are formed by "ligand exchange" reactions of X · (HO) clusters with HOCl molecules at low pressure (∼10 mbar) in a radio frequency ion guide. The spectra generally feature many bands in addition to the fundamentals expected at the double harmonic level.

Preparation and Characterization of the Halogen-Bonding Motif in the Isolated Cl·IOH Complex with Cryogenic Ion Vibrational Spectroscopy.

In the presence of a halide ion, hypohalous acids can adopt two binding motifs upon formation of the ion-molecule complexes [XHOY] (X, Y = Cl, Br, I): a hydrogen (HB) bond to the acid OH group and a halogen (XB) bond between the anion and the acid halogen. Here we isolate the X-bonded Cl·IOH ion-molecule complex by collisions of I·(HO) clusters with HOCl vapor and measure its vibrational spectrum by IR photodissociation of the H-tagged complex. Anharmonic analysis of its vibrational band pattern reveals that formation of the XB complex results in dramatic lowering of the HOI bending fundamental frequency and elongation of the O-I bond (by 168 cm and 0.

A flexible approach to vibrational perturbation theory using sparse matrix methods.

A sparse linear algebra based implementation of Rayleigh-Schrödinger vibrational perturbation theory is presented. This implementation allows for flexibility in the coordinates used to expand the vibrational Hamiltonian as well as the order to which the perturbation theory is performed. It also provides a powerful tool for investigating the origin of spectral intensity and transition frequencies.

Infrared spectroscopic signature of a hydroperoxyalkyl radical (•QOOH).

Infrared (IR) action spectroscopy is utilized to characterize a prototypical carbon-centered hydroperoxyalkyl radical (•QOOH) transiently formed in the oxidation of volatile organic compounds. The •QOOH radical formed in isobutane oxidation, 2-hydroperoxy-2-methylprop-1-yl, •CH(CH)COOH, is generated in the laboratory by H-atom abstraction from tert-butyl hydroperoxide (TBHP). IR spectral features of jet-cooled and stabilized •QOOH radicals are observed from 2950 to 7050 cm at energies that lie below and above the transition state barrier leading to OH radical and cyclic ether products.

Coupling of torsion and OH-stretching in tert-butyl hydroperoxide. I. The cold and warm first OH-stretching overtone spectrum.

The infrared (IR) spectrum of tert-butyl hydroperoxide (TBHP) in the region of the first OH-stretching overtone has been observed under jet-cooled and thermal (300 K, 3 Torr) conditions at ∼7017 cm. The jet-cooled spectrum is recorded by IR multiphoton excitation with UV laser-induced fluorescence detection of OH radical products, while direct IR absorption is utilized under thermal conditions. Prior spectroscopic studies of TBHP and other hydroperoxides have shown that the OH-stretch and XOOH (X = H or C) torsion vibrations are strongly coupled, resulting in a double well potential associated with the torsional motion about the OO bond that is different for each of the OH-stretching vibrational states.

Coupling of torsion and OH-stretching in tert-butyl hydroperoxide. II. The OH-stretching fundamental and overtone spectra.

The vibrational spectra of gas phase tert-butyl hydroperoxide have been recorded in the OH-stretching fundamental and overtone regions (Δv = 1-5) at room temperature using conventional Fourier transform infrared (Δv = 1-3) and cavity ring-down (Δv = 4-5) spectroscopy. In hydroperoxides, the OH-stretching and COOH torsion vibrations are strongly coupled. The double-well nature of the COOH torsion potential leads to tunneling splitting of the energy levels and, combined with the low frequency of the torsional vibration, results in spectra in the OH-stretching regions with multiple vibrational transitions.

Legionella-Infected Macrophages Engage the Alveolar Epithelium to Metabolically Reprogram Myeloid Cells and Promote Antibacterial Inflammation.

Alveolar macrophages are among the first immune cells that respond to inhaled pathogens. However, numerous pathogens block macrophage-intrinsic immune responses, making it unclear how robust antimicrobial responses are generated. The intracellular bacterium Legionella pneumophila inhibits host translation, thereby impairing cytokine production by infected macrophages.

Diffusion Monte Carlo Studies on the Detection of Structural Changes in the Water Hexamer upon Isotopic Substitution.

The ground-state structures of water hexamer and several deuterated variants are studied by using the diffusion Monte Carlo (DMC) method. We demonstrate that a recently developed guided DMC approach allows us to study these systems using substantially smaller ensembles than are required for standard DMC approaches. DMC calculations of the ground states of (HO) and (DO) using the MB-pol potential with 50 000 walkers and a 1 au time step show that for (HO) the cage structure is 51 ± 7 cm lower in energy than the prism structure.

The Role of Tunneling in the Spectra of H and D up to 7300 cm.

The spectra for H and D are extended to cover the region between 4830 and 7300 cm. These spectra are obtained using mass-selected photodissociation spectroscopy. To understand the nature of the states that are accessed by the transitions in this and prior studies, we develop a four-dimensional model Hamiltonian.

Beyond Badger's Rule: The Origins and Generality of the Structure-Spectra Relationship of Aqueous Hydrogen Bonds.

The structure of hydrogen bonded networks is intimately intertwined with their dynamics. Despite the incredibly wide range of hydrogen bond strengths encountered in water clusters, ion-water clusters, and liquid water, we demonstrate that the previously reported correlation between the change in the equilibrium bond length of the hydrogen bonded OH covalent bond and the corresponding shift in its harmonic frequency in water clusters is much more broadly applicable. Surprisingly, this correlation describes the ratios for both the equilibrium OH bond length/harmonic frequency and the vibrationally averaged bond length/anharmonic frequency in water, hydronium water, and halide water clusters.

Age-related differences in IL-1 signaling and capsule serotype affect persistence of Streptococcus pneumoniae colonization.

Young age is a risk factor for prolonged colonization by common pathogens residing in their upper respiratory tract (URT). Why children present with more persistent colonization is unknown and there is relatively little insight into the host-pathogen interactions that contribute to persistent colonization. To identify factors permissive for persistent colonization during infancy, we utilized an infant mouse model of Streptococcus pneumoniae colonization in which clearance from the mucosal surface of the URT requires many weeks to months.

Broad detection of bacterial type III secretion system and flagellin proteins by the human NAIP/NLRC4 inflammasome.

Inflammasomes are cytosolic multiprotein complexes that initiate host defense against bacterial pathogens by activating caspase-1-dependent cytokine secretion and cell death. In mice, specific nucleotide-binding domain, leucine-rich repeat-containing family, apoptosis inhibitory proteins (NAIPs) activate the nucleotide-binding domain, leucine-rich repeat-containing family, CARD domain-containing protein 4 (NLRC4) inflammasome upon sensing components of the type III secretion system (T3SS) and flagellar apparatus. NAIP1 recognizes the T3SS needle protein, NAIP2 recognizes the T3SS inner rod protein, and NAIP5 and NAIP6 recognize flagellin.

Neutrophils and Ly6Chi monocytes collaborate in generating an optimal cytokine response that protects against pulmonary Legionella pneumophila infection.

Early responses mounted by both tissue-resident and recruited innate immune cells are essential for host defense against bacterial pathogens. In particular, both neutrophils and Ly6Chi monocytes are rapidly recruited to sites of infection. While neutrophils and monocytes produce bactericidal molecules, such as reactive nitrogen and oxygen species, both cell types are also capable of synthesizing overlapping sets of cytokines important for host defense.

Primary Role for Toll-Like Receptor-Driven Tumor Necrosis Factor Rather than Cytosolic Immune Detection in Restricting Coxiella burnetii Phase II Replication within Mouse Macrophages.

Coxiella burnetii replicates within permissive host cells by employing a Dot/Icm type IV secretion system (T4SS) to translocate effector proteins that direct the formation of a parasitophorous vacuole. C57BL/6 mouse macrophages restrict the intracellular replication of the C. burnetii.