Exploring the Isomer Landscape, Fragment Additivity, and Vibrational Signatures of the Z-Alanine Protected Amino Acid Derivative

The Journal of Physical Chemistry A · 2026-01-29 · 1 citations

The N-benzyloxycarbonyl-l-alanine molecule is a derivative of the l-α-alanine amino acid with a benzyl carbamate protecting group at the N-terminus, more commonly denoted Cbz-Ala or Z-Ala. In this computational investigation, we sought to determine the available isomers of Z-Ala and their distinguishing spectroscopic signatures via quantum-chemistry methods. Sixty-five total isomers were obtained, and coupled-cluster- and perturbation-theory-based relative energies were computed. The two nearly degenerate, lowest-energy isomers were found to differ in their configuration than the lowest-energy form of isolated alanine, suggesting that the protecting group changes the dominant form of Ala. Through comparisons to exhaustive sampling of Ala and benzyl formate isomers, nearly all of the Z-Ala structures could be ascribed to fragment-paired structural motifs, with a few outliers exhibiting new intramolecular interactions between the constituent fragments. Based on this observation, an assessment of the additivity of the two fragments’ relative energies was performed for Z-Ala energies. Many of the isomers’ energies were reasonably described by such considerations, although backbone strain and hydrogen-bonding interactions altered this energy landscape and led to nonadditive effects for several of the isomers. Comparison to experimental REMPI-based UV/IR ion-dip vibrational spectra in the 90–1822 cm–1 region indicated that two isomers are dominantly present at the experimental conditions, although signatures of other isomers from the ensemble were also observed. Clear assignments of structural motifs were possible through this experimental comparison. Computed coupled-cluster benchmarks allowed for methodology assessments in this study. The modified opposite-spin MP2 method (MOS-RI-MP2) was found to be particularly accurate, relative to these benchmarks, after minor adjustment of the range-separation parameter. Density functional theory (DFT) methods were found to be variable in their accuracy for both energies and spectra, although a few key functionals performed particularly well for this system in the low-frequency region of the vibrational spectrum. These methodology constraints provided recommendations for similar systems and subsequent anharmonic analyses.

Converging the <b> <i>n</i> </b> -Mode Representation of Anharmonic Molecular Vibrations via Local Modes

Journal of Chemical Theory and Computation · 2026-04-28

cluster, 290- and 590-fold computational accelerations, respectively, were observed, and these accelerations should increase for larger systems. This computational efficiency was achieved while retaining subwavenumber fidelity with the results of cutoff-free simulations.

Contact Dermatitis and Patch Testing Education: A Work Group Report From the Allergic Skin Diseases Committee of the AAAAI

The Journal of Allergy and Clinical Immunology In Practice · 2025-05-15 · 1 citations

Assessing the environmental influence on ‘local-monomer’ vibrational spectra via many-body potentials

Molecular Physics · 2025-04-29 · 1 citations

Association of clinical manifestations and immune alterations with genetic variants of uncertain significance in patients concerned for inborn errors of immunity

Clinical Immunology · 2025-05-10 · 1 citations

Infrared multiple photon dissociation spectra of cesiated complexes of the aliphatic amino acids: Challenges for conformational-space calculations by density functional theory

International Journal of Mass Spectrometry · 2024-01-26 · 3 citations

Reductive amination of carbonyl C–C bonds enables formal nitrogen insertion

ChemRxiv · 2024-07-24 · 2 citations

Given its ubiquity in various biological and physical processes1–3, the reductive amination of ketones and aldehydes is one of the oldest and most widely used methods for amine synthesis4. As a cornerstone of synthetic chemistry, it has largely remained unchanged since its discovery over a century ago5. Herein, we report the mechanistically-driven development of a complementary reaction, which reductively aminates the C–C σ-bond attached to carbonyls, not the carbonyl C–O π-bond, generating value-added linear and cyclic 3° amines in a modular fashion. Critical to the success of this endeavor were mechanistic insights that enabled us to modulate the resting state of a borane catalyst, minimize deleterious disproportionation of a hydroxylamine nitrogen source, and control the migratory selectivity of a key nitrenoid reactive intermediate. Experimental evidence support the reaction occurring through a reductive amination/stepwise reductive Stieglitz cascade, via a ketonitrone, which can be interrupted under catalyst-control to generate valuable N,N-disubstituted hydroxylamines. The method reported herein enables various net transformations that would otherwise require lengthy synthetic sequences using pre-existing technologies. This is highlighted by its application to a two-step protocol for the formal insertion of a single nitrogen atom into the core framework of abundant hydrocarbon feedstocks, the site-selective late-stage C–C amination of complex molecules, diversity-oriented synthesis of isomeric amines from a single precursor, and transposition of nitrogen to different positions within a heterocycle.

The Near-Sightedness of Many-Body Interactions in Anharmonic Vibrational Couplings

Journal of the American Chemical Society · 2024-05-21 · 5 citations

Couplings between vibrational motions are driven by electronic interactions, and these couplings carry special significance in vibrational energy transfer, multidimensional spectroscopy experiments, and simulations of vibrational spectra. In this investigation, the many-body contributions to these couplings are analyzed computationally in the context of clathrate-like alkali metal cation hydrates, including Cs+(H2O)20, Rb+(H2O)20, and K+(H2O)20, using both analytic and quantum-chemistry potential energy surfaces. Although the harmonic spectra and one-dimensional anharmonic spectra depend strongly on these many-body interactions, the mode-pair couplings were, perhaps surprisingly, found to be dominated by one-body effects, even in cases of couplings to low-frequency modes that involved the motion of multiple water molecules. The origin of this effect was traced mainly to geometric distortion within water monomers and cancellation of many-body effects in differential couplings, and the effect was also shown to be agnostic to the identity of the ion. These outcomes provide new understanding of vibrational couplings and suggest the possibility of improved computational methods for the simulation of infrared and Raman spectra.

IR spectroscopic characterization of [M,C,2H]⁺ (M = Ru and Rh) products formed by reacting 4d transition metal cations with oxirane: Spectroscopic evidence for multireference character in RhCH₂⁺

Physical Chemistry Chemical Physics · 2024-01-01 · 6 citations

A combination of infrared multiple-photon dissociation (IRMPD) action spectroscopy and quantum chemical calculations was employed to investigate the [M,C,2H] + (M = Ru and Rh) species.

Accelerating and stabilizing the convergence of vibrational self-consistent field calculations via the direct inversion of the iterative subspace (vDIIS) algorithm

The Journal of Chemical Physics · 2023-08-22 · 3 citations

The vibrational self-consistent field (VSCF) method yields anharmonic states and spectra for molecular vibrations, and it serves as the starting point for more sophisticated correlated-vibration methods. Convergence of the iterative, non-linear optimization in VSCF calculations can be erratic or altogether unsuccessful, particularly for chemical systems involving low-frequency motions. In this work, a vibrational formulation of the Direct Inversion of the Iterative Subspace method of Pulay is presented and investigated. This formulation accounts for distinct attributes of the vibrational and electronic cases, including the expansion of each single-mode vibrational wavefunction in its own basis set. The resulting Direct Inversion of the Iterative Subspace method is shown to substantially accelerate VSCF convergence in all convergent cases as well as rectify many cases where Roothaan-based methods fail. Performance across systems ranging from small, rigid molecules to weakly bound molecular clusters is investigated in this analysis.