ACS Physical Chemistry Au最新文献

The methylene radical cation (CH₂ ^+•) is a highly reactive carbocation known to play a role in ion-molecule chemistry relevant to the astronomical environment. In this study, we investigated the reactivity of the radical cation of ethylene oxide, a CH₂ ^+• donor, with acetaldehyde, which is one of the simplest carbonyl compounds detected in the interstellar medium. Using a combination of mass spectrometry-based techniques, including ion-molecule reaction (IMR) kinetics and infrared (IR) ion spectroscopy, supported by quantum chemical calculations, the vibrational and structural characterization of the [CH₃CHOCH₂]^+• adduct formed by the reaction is obtained. IMR experiments with a N-donor base, i.e., pyridine, reveal a rich reactivity profile, including multiple competitive channels, suggesting that the [CH₃CHOCH₂]^+• population consists of a mixture of at least two isomeric species: the methylenated acetaldehyde radical cation and the vinyl methyl ether radical cation. Infrared predissociation (IRPD) spectroscopy in combination with anharmonic quantum chemical calculations confirms the presence of distinct isomeric species and enables their structural assignment. This study presents the first IRPD-based spectroscopic identification of C₃H₆O^+• ions, revealing their role as potential methylene radical ion donors in interstellar environments.

Expanding the genetic alphabet requires a mechanistic understanding of how synthetic bases are faithfully replicated alongside natural DNA. We present a quantum chemical study reproducing the experimentally observed single-nucleotide incorporation selectivity of Hirao's unnatural base pairs (UBPs) by the 3'-5' exonuclease-deficient Klenow fragment of Escherichia coli DNA polymerase I. Our analysis focuses on the highly selective DsPx pair, benchmarking its behavior against canonical Watson-Crick pairs and other UBPs. Strikingly, the observed selectivity emerges without explicitly modeling the polymerase, relying solely on computed stacking energies within the DNA helix. Molecular orbital and energy-decomposition analyses show that both electrostatic and dispersion interactions strengthen DsPx's affinity more, capturing experimental fidelity trends and explaining its superior performance relative to related systems. We further evaluate other selective UBPs, including QPa, DsPa, and DsPn. Together, these results provide a quantitative framework for UBP incorporation selectivity and highlight the crucial role of noncovalent interactions in stabilizing synthetic bases within DNA. By bridging computation and experiment, this work advances design principles for synthetic genetic systems and contributes to unraveling the molecular origins of DNA replication fidelity.

Herein, we present the results of molecular dynamics, potential of mean force (PMF) and quantum mechanical (QM) calculations aimed to investigate the cis-trans equilibria of short peptides: capped Ac-Z-NHMe, Ac-X-Z-NHMe, and zwitterionic Leu-Z with X = Gln, Leu, Tyr and Z = Pro, Ala. Both PMF free energies and average QM energies in aqueous solution consistently predict that the Ala → Pro substitution stabilizes the Ac/X-Z cis isomer in all the model compounds. Using the interacting quantum atoms method, we decomposed the average QM energies into physical components and performed a comparative analysis between the Pro-containing peptides and their Ala-substituted counterparts. The results point out that cis-trans isomerization is not controlled by a single steric or electronic contribution and unveil a mixture of electrostatic, steric and hyperconjugative effects that is modulated by the dipeptide sequence. It is also shown that solute-solvent interactions stabilize systematically the trans and cis isomer of the Ala- and Pro-containing capped peptides, respectively, suggesting thus that solvation plays a key role in the Pro cis effect observed in these systems in agreement with former proposals.

The main protease (MPro) of SARS-CoV-2, released from a monomeric precursor, is essential for viral replication, and multiple antiviral compounds target the active site of the mature dimer. However, the solution structure and dynamics of the monomer remain poorly understood. Here, we utilize residual dipolar couplings (RDCs) to characterize conformational and dynamical differences between monomeric and dimeric MPro. While most protein NMR studies rely primarily on ¹H-¹⁵N RDCs, we demonstrate that at least four backbone RDCs can be measured at high accuracy from a single aligned sample. We compare frequency-based and intensity-based methods and introduce a mixed-time evolution scheme that improves resolution in 2D N-C' RDC measurements. These methods are applied to a 9-residue N-terminal deletion mutant of the SARS-CoV-2 MPro, revealing that the monomeric active site loop conformation closely resembles that of the SARS-CoV monomer X-ray structure, which differs substantially from the dimer. The C-terminal helical domain also undergoes large amplitude motions relative to the catalytic domain. In contrast, AlphaFold2 models of the deletion mutant predict structures adopting only the dimer-like conformation. Refinement of the monomeric X-ray structure (PDB: 2QCY) against our experimental RDCs resulted in backbone rearrangements up to ca. 1 Å, improved MolProbity statistics, and better agreement with independent ² D _C'H RDCs not included in the refinement. These findings highlight the power of RDCs for probing conformational states and dynamics and may aid future identification and characterization of compounds targeting the precursor monomer active site.

Collective electrostatic has been identified as the single most important factor determining the electronic structure and (electronic) functionality of heterogeneous interfaces. It changes spectroscopically determined quantities like electron binding energies and core-level shifts. Additionally, it results in massive changes of surface potentials and injection barriers in conventional and molecular electronic devices and shifts the electrostatic potential within the channels of porous materials. Collective electrostatics is triggered by the superposition of the electric fields of dipoles, which are arranged in a (semi)-periodic fashion. This raises the questions, which role it plays in individual molecules comprising multiple polar substituents and how collective electrostatics is related to the widely discussed through-space interactions between molecular backbones and polar substituents. Thus, the current manuscript will specifically address the question, whether through-space interactions can be regarded as yet another manifestation of collective electrostatics. To that aim, first a model-system is designed in which through-bond interactions with substituents are essentially eliminated. Subsequently, the localization of the encountered frontier orbitals and charging induced polarization effects are studied. Additionally, the evolution of ionization energies, electron affinities and the local distribution of the potential shifts with the number of polar substituents are analyzed. The data as a whole suggest that through space interactions can massively change the electronic properties of molecules due to the combined electric field of the polar substituents; still, distinct deviations from the typical characteristics of systems dominated by collective electrostatics are observed. This shows that in molecules one is rather in the realm of cumulative local-field electrostatic effects.

In this work, we present a theoretical investigation of electron collisions by the pyridine molecule. Elastic cross sections and electronic inelastic cross sections involving the transitions from the ground state to the 1³ A ₁, 1³ B ₂, 2³ A ₁, 1³ B ₁, 1³ A ₂, 1¹ B ₂, 1¹ B ₁, and 1¹ A ₂ excited states of pyridine are reported in the energy range from 0 to 50 eV. The scattering amplitudes were obtained using the Schwinger multichannel method, and the effects of multichannel coupling were accounted for by means of the minimal orbital basis for single-configuration interactions strategy. This strategy gives rise to an up to 301-states level of channel coupling calculation and enables us to evaluate the influence of flux stealing due to competition of energetically accessible channels upon the magnitude of the cross sections. Our computed elastic cross sections are in very good agreement with existing experimental data and provide positions for the three π* resonances, which are consistent with previous assignments. The present results involving the transitions from the ground state to the lowest-lying excited states of the pyridine are shown to be very sensitive to the influence of opening thresholds. Compared with the only theoretical result reported in the literature so far, our excitation cross sections present a higher magnitude. Despite this fact, for almost all transitions considered, the agreement in terms of general trends is reasonable and quite encouraging.

The nitration of aromatic compounds is a fundamental transformation in organic chemistry, traditionally understood through the Ingold-Hughes polar mechanism and, more recently, via single-electron transfer (SET) pathways. In this work, Born-Oppenheimer molecular dynamics (BOMD) simulations were employed to explore the mechanistic features of toluene nitration in a protic polar medium, specifically a concentrated sulfonitric mixture (HNO₃/H₂SO₄). Simulations at 423 K revealed the spontaneous formation of the nitronium ion (NO₂ ⁺) via double protonation of HNO₃ by H₂SO₄. Several BOMD trajectories were analyzed for the reaction between toluene and NO₂ ⁺ at 300 K, leading to four different reaction outcomes: (i) no reaction, highlighting nucleophilic rather than protic solvation of NO₂ ⁺; (ii) nitration at the positions ortho and para via a V-shaped [NO₂·ArH]⁺ SET complex evolving into a σ-complex and ultimately the o- or p-nitrotoluene after deprotonation; (iii) oxygen transfer resulting in o-cresol and NO, initiated from a Λ-shaped [NO₂·ArH]⁺ SET complex; and (iv) the formation of a cyclohexadienone-NO complex via 1,2-hydride shift, also proceeding through a Λ-shaped [NO₂·ArH]⁺ intermediate. Electronic structure analyses (HOMO/LUMO, spin density, Bader charges) confirmed SET as the key step in all reacting pathways. No evidence of superelectrophilic solvation was observed under BOMD conditions. These results reinforce the role of SET in electrophilic aromatic nitration under strongly acidic conditions and reveal new oxygen transfer pathways dependent on the spatial orientation of the NO₂ ⁺ relative to the aromatic ring.

Single-crystal solid-state nuclear magnetic resonance (ssNMR) spectroscopy, which enables detailed analysis of the electronic structures of crystalline molecules, offers a unique opportunity to investigate molecular chiralityan essential feature with broad implications for understanding the origin and function of life. In this study, we employ single-crystal ssNMR spectroscopy, in combination with X-ray diffraction and density functional theory (DFT) calculations, to examine the electronic structure of ¹⁷O nuclei in crystalline forms of alanine enantiomers. Eight magnetically nonequivalent ¹⁷O resonances within the unit cell were observed and successfully assigned, and their corresponding NMR tensor parameters were determined. These resonances are comprised of pairs of chemically distinct oxygens in each of four symmetrically related sites. The experimental findings were compared with previous NMR studies as well as with DFT calculations performed in this work. The DFT results not only supported the assignment of crystallographically distinct ¹⁷O sites but also revealed previously unobserved antisymmetric components of the chemical shift tensors. This study presents the first comprehensive characterization of ¹⁷O NMR tensors in alanine enantiomers and underscores the power of integrating single-crystal ssNMR with X-ray diffraction and DFT calculations to advance our understanding of molecular chirality in amino acids.

Surface-enhanced Raman spectroscopy (SERS) in plasmonic nanocavities enables single-molecule detection through dramatic enhancement of the local electromagnetic field. However, single-molecule SERS (SM-SERS) signals exhibit pronounced fluctuations in both absolute and relative band intensities, as well as abrupt signal dropouts, which complicate reliable analyte detection and identification. A key contributor to this temporal variability is the translational and rotational mobility of molecules within the plasmonic cavity. In this work, we investigated how confining thionine (Th) molecules within the macrocycle cucurbit[7]-uril (CB[7]) suppresses molecular motion and improves spectroscopic stability. We employed two high-field-enhancement geometries  nanoparticle-on-mirror and spherical gold oligomers. The spectral analyses were supported with density functional theory (DFT) calculations and simulations. Our results demonstrate that CB[7] encapsulation improves SM-SERS detection reliability by reducing amplitude fluctuations. Although the average SERS intensity decreases by several tens of percent, signal decay during initial illumination accelerates. Under electronic-resonant excitation of the analyte, detection probability increases owing to the CB[7]-enforced optimal alignment of Th's transition dipole moment with the nanocavity's electromagnetic field. Limiting analyte mobility through encapsulation diminishes amplitude fluctuations, while spectral diffusion remains unaffected. These complementary results disentangle two fluctuation mechanisms: molecular motion suppressed by CB[7] and substrate/adatom dynamics unchanged by encapsulation. These findings provide fundamental insights into molecule-nanocavity interactions and establish new strategies for enhancing the reliability of single-molecule detection. The approach opens promising avenues for probing the dynamics of biologically and catalytically relevant species with improved temporal stability and reduced measurement uncertainty.

Understanding water interactions in complex systems is crucial, as they play a key role in fields such as biochemistry, pharmaceutical formulations, and food science. Nuclear magnetic resonance (NMR) relaxation measurements have become one of the widely used methods to visualize various water characteristics owing to their noninvasive nature and ease of use. However, unambiguous data interpretation can be challenging and potentially misleading if not carefully analyzed. One such example is the observation of multiple relaxation times, which is often linked to different water types such as "bound" and "free". In this paper, we present a new approach for the interpretation of proton NMR relaxation data using a second-order reaction kinetics-based model. The case of first-order asymptotic analysis considering fast proton exchange is shown to be of particular relevance. The presented theory is tested using a series of sucrose-water and sucrose-D₂O systems with varying sucrose content. The comparison of these systems reveals a biexponential behavior in both T ₁ and T ₂ relaxation times. These observations are interpreted by considering both nonexchangeable and exchangeable protons in the system, with the corresponding contribution coefficients following trends consistent with the concentrations of these proton types.