Vibrational mode tailoring approach: an efficient route to compute anharmonic molecular vibrations of large molecules.

In this study, an efficient route to compute the multidimensional potential energy surfaces (PESs) for the description of quantum anharmonic molecular vibrations is presented. For large molecular systems, where the number of inter mode coupling terms are substantial, a tailor-made construction of truncated PESs is suggested which suitably avoids computation of full PESs by quantitative assessment of the atomic displacements during the normal mode of vibrations. It is shown that, typically, when two normal modes of vibrations are sharing the same atoms, the mode-mode coupling strength is generally large and can be included for truncated PESs.

Performance of Effective Harmonic Oscillator Approach for the Calculations of Vibrational Transition Energies of Large Molecules.

The accuracy and performance of the effective harmonic oscillator approximation for the description of anharmonic vibrational structure calculations are tested for large molecular systems and compared with experimental values along with vibrational self-consistent field and second-order perturbation theories. The effective harmonic oscillator approach is an effective single-particle approximation where the variational parameters are the centroids and widths of the multidimensional Gaussian product functions posited as the vibrational wave functions. A comprehensive calculation for 849 transitions that include the fundamentals, two and three quanta overtone transitions, and several combination bands of three polyaromatic hydrocarbons and one DNA nucleobase with a total of 231 normal modes are assessed.

Accuracy of Different Electronic Basis Set Families for Anharmonic Molecular Vibrations: A Comprehensive Benchmark Study.

In this work, the accuracy and convergence of different electronic basis set families for the computation of anharmonic molecular vibrational spectroscopic calculations are benchmarked. A series of 39 different basis sets from different families following their hierarchy are assessed on VSCF and VSCF-PT2 algorithms with commonly used MP2 and DFT based B3LYP-D potentials for a set of molecular systems. Such an effort has been validated in a previous work ( 2020, 124, 9203-9221) with split-valence basis sets for fundamentals and intensities.

Performance of Vibrational Self-Consistent Field Theory for Accurate Potential Energy Surfaces: Fundamentals, Excited States, and Intensities.

The performance of vibrational structure calculations beyond harmonic approximation in the framework of the vibrational self-consistent field method with second-order perturbation corrections (VSCF-PT2) is investigated in conjunction with very accurate potential energy surfaces (PESs) given by various coupled-cluster electronic structure theories. The quality of anharmonic calculations depends on the accuracy of the underlying multidimensional PES obtained from its functional form, which is given by the level of electronic structure theory. Two such highest levels of typical coupled-cluster electronic structure methods, CCSD and the ″gold standard″ CCSD(T), along with their variants such as CCD, CR-CCL (completely renormalized CR-CC(2,3) approach), and CCSD(TQ) are tested for the construction of accurate anharmonic potentials without any fitting or ad hoc scaling and using cc-pVTZ basis sets.

Comprehensive Benchmark Results for the Accuracy of Basis Sets for Anharmonic Molecular Vibrations.

The accuracy and convergence of a series of commonly used split-valence electronic basis sets are systematically investigated for the anharmonic molecular vibrational spectroscopic calculations using the second-order perturbative corrected vibrational self-consistent field theory. A series of 18 split-valence basis sets with increasing flexibility is assessed in conjunction with MP2 and density functional theory (DFT)-based dispersion-corrected B3LYP potentials and applied to a set of molecular systems with different electronic and vibrational characteristics. The computed fundamental transitions and intensities are compared with the experimental values to assess the accuracy of different basis sets.

Dual Basis Approach for Ab Initio Anharmonic Calculations of Vibrational Spectroscopy: Application to Microsolvated Biomolecules.

A dual electronic basis set approach is introduced for more efficient but accurate calculations of the anharmonic vibrational spectra in the framework of the vibrational self-consistent field (VSCF) theory. In this approach, an accurate basis set is used to compute the vibrational spectra at the harmonic level. The results are used to scale the potential surface from a more modest but much more efficient basis set.

Azo-dyes based small bifunctional molecules for metal chelation and controlling amyloid formation.

Chemical tools are needed to discover new effective drugs for tackling multifaceted complex neurodegenerative diseases like Alzheimer's disease (AD). Multifunctional nature of two compounds, 5-((4-nitro-phenyl)diazenyl)quinolin-8-ol (HL1) and 4-((4-nitrophenyl)diazenyl)benzene-1,3-diol (HL2) is reported w.r.

Intrinsic structure of pentapeptide Leu-enkephalin: geometry optimization and validation by comparison of VSCF-PT2 calculations with cold ion spectroscopy.

The intrinsic structure of an opioid peptide [Ala2, Leu5]-leucine enkephalin (ALE) has been investigated using first-principles based vibrational self-consistent field (VSCF) theory and cold ion spectroscopy. IR-UV double resonance spectroscopy revealed the presence of only one highly abundant conformer of the singly protonated ALE, isolated and cryogenically cooled in the gas phase. High-level quantum mechanical calculations of electronic structures in conjunction with a systematic conformational search allowed for finding a few low-energy candidate structures.

Hypochlorite-Mediated Modulation of Photoinduced Electron Transfer in a Phenothiazine-Boron dipyrromethene Electron Donor-Acceptor Dyad: A Highly Water Soluble "Turn-On" Fluorescent Probe for Hypochlorite.

A highly water-soluble phenothiazine (PTZ)-boron dipyrromethene (BODIPY)-based electron donor-acceptor dyad (WS-Probe), which contains BODIPY as the signaling antennae and PTZ as the OCl reactive group, was designed and used as a fluorescent chemosensor for the detection of OCl . Upon addition of incremental amounts of NaOCl, the quenched fluorescence of WS-Probe was enhanced drastically, which indicated the inhibition of reductive photoinduced electron transfer (PET) from PTZ to BODIPY*; the detection limit was calculated to be 26.7 nm.

Catalyst-Controlled Structural Divergence: Selective Intramolecular 7-endo-dig and 6-exo-dig Post-Ugi Cyclization for the Synthesis of Benzoxazepinones and Benzoxazinones.

Metal catalyzed post-Ugi cyclization of bis-amides is reported in this study. Exposure of bis-amides to Pd(II) catalyst triggered the formation of seven-membered benzoxazepinones. This investigation established that changing the catalyst to a Echavarren's gold(I) turned off cyclization to seven member ring and turned on 6-exo-dig annulations to afford family of six-membered benzoxazinones.

A Decapeptide Hydrated by Two Waters: Conformers Determined by Theory and Validated by Cold Ion Spectroscopy.

The intrinsic structures of biomolecules in the gas phase may not reflect their native solution geometries. Microsolvation of the molecules bridges the two environments, enabling a tracking of molecular structural changes upon hydration at the atomistic level. We employ density functional calculations to compute a large pool of structures and vibrational spectra for a gas-phase complex, in which a doubly protonated decapeptide, gramicidin S, is solvated by two water molecules.

Ruthenium Catalyzed Intramolecular C-S Coupling Reactions: Synthetic Scope and Mechanistic Insight.

A ruthenium catalyzed intramolecular C-S coupling reaction of N-arylthioureas for the synthesis of 2-aminobenzothiazoles has been developed. Kinetic, isotope labeling, and computational studies reveal the involvement of an electrophilic ruthenation pathway instead of a direct C-H activation. Stereoelectronic effect of meta-substituents on the N-arylthiourea dictates the final regioselective outcome of the reaction.

First-principles anharmonic quantum calculations for peptide spectroscopy: VSCF calculations and comparison with experiments.

First-principles quantum calculations for anharmonic vibrational spectroscopy of three protected dipeptides are carried out and compared with experimental data. Using hybrid HF/MP2 potentials, the Vibrational Self-Consistent Field with Second-Order Perturbation Correction (VSCF-PT2) algorithm is used to compute the spectra without any ad hoc scaling or fitting. All of the vibrational modes (135 for the largest system) are treated quantum mechanically and anharmonically using full pair-wise coupling potentials to represent the interaction between different modes.

Mechanistic studies of malonic acid-mediated in situ acylation.

We have previously introduced an easy to perform, cost-effective and highly efficient acetylation technique for solid phase synthesis (SPPS). Malonic acid is used as a precursor and the reaction proceeds via a reactive ketene that acetylates the target amine. Here we present a detailed mechanistic study of the malonic acid-mediated acylation.

Conformational structures of a decapeptide validated by first principles calculations and cold ion spectroscopy.

Calculated structures of the two most stable conformers of a protonated decapeptide gramicidin S in the gas phase have been validated by comparing the vibrational spectra, calculated from first- principles and measured in a wide spectral range using infrared (IR)-UV double resonance cold ion spectroscopy. All the 522 vibrational modes of each conformer were calculated quantum mechanically and compared with the experiment without any recourse to an empirical scaling. The study demonstrates that first-principles calculations, when accounting for vibrational anharmonicity, can reproduce high-resolution experimental spectra well enough for validating structures of molecules as large as of 200 atoms.

Approximate first-principles anharmonic calculations of polyatomic spectra using MP2 and B3LYP potentials: comparisons with experiment.

Anharmonic vibrational spectroscopy calculations using MP2 and B3LYP computed potential surfaces are carried out for a series of molecules, and frequencies and intensities are compared with those from experiment. The vibrational self-consistent field with second-order perturbation correction (VSCF-PT2) is used in computing the spectra. The test calculations have been performed for the molecules HNO3, C2H4, C2H4O, H2SO4, CH3COOH, glycine, and alanine.

A tandem in situ peptide cyclization through trifluoroacetic acid cleavage.

We present a new approach for peptide cyclization during solid phase synthesis under highly acidic conditions. Our approach involves simultaneous in situ deprotection, cyclization and trifluoroacetic acid (TFA) cleavage of the peptide, which is achieved by forming an amide bond between a lysine side chain and a succinic acid linker at the peptide N-terminus. The reaction proceeds via a highly active succinimide intermediate, which was isolated and characterized.

A highly efficient in situ N-acetylation approach for solid phase synthesis.

We describe a new general N-acetylation method for solid phase synthesis. Malonic acid is used as a precursor and the reaction proceeds by in situ formation of a reactive ketene intermediate at room temperature. We have successfully applied this methodology to peptides and non-peptidic molecules containing a variety of functional groups.

Vibrational self-consistent field calculations for spectroscopy of biological molecules: new algorithmic developments and applications.

This review describes the vibrational self-consistent field (VSCF) method and its other variants for computing anharmonic vibrational spectroscopy of biological molecules. The superiority and limitations of this algorithm are discussed with examples. The spectroscopic accuracy of the VSCF method is compared with experimental results and other available state-of-the-art algorithms for various biologically important systems.

Development of a new variational approach for thermal density matrices.

A McLachlan-type variational principle is derived for thermal density matrices. In this approach, the trace of the mean square of the differences between the derivatives of the exact and model density matrices is minimized with respect to the parameters in the model Hamiltonian. Applications to model anharmonic systems in the independent particle model show that the method can provide thermodynamic state functions accurately (within 5% of the converged basis set results) and at the same level of accuracy as the results using Feynman-Gibbs-Bogoliubov variational principle at this level of approximation.

A thermal self-consistent field theory for the calculation of molecular vibrational partition functions.

A new approach for the calculation of anharmonic molecular vibrational partition functions is developed based on a separable ansatz to the thermal density matrix. The parameters appearing in the effective single particle Hamiltonians that generate the thermal density matrices are determined variationally. The resulting equations are the thermal analogs of the vibrational self-consistent field approximation.