Search Results (58)

The utilization and chemical transformation of carbon dioxide remains a pressing problem in modern chemistry. Numerous experimental and theoretical studies have focused on the interaction of CO₂ with amines. In this work, quantum chemical density functional theory (DFT) calculations of equilibrium geometries, energies, electronic and vibrational characteristics of CO₂-sensitive mono-, di-, tris-hydroxyamidines and their associates were carried out by the B3LYP/6-31G(d, p) method. The harmonic vibrational frequencies were scaled and compared with the experimental FTIR spectra for supporting wavenumber assignments. Natural bond orbital (NBO) analysis of the atomic charges and charge delocalization was employed to investigate the nature of hydrogen bonding in hydroxyamidine associates. We also used the intrinsically polarizable continuum model (IEFPCM), and the DFT-D3 method was applied to account for dispersion effects during associate formation. Using the 6-311+G(2d, p) basis set for tris-hydroxyamidine, and its adducts, a comparative analysis of the experimental and calculated ¹H NMR spectra was performed. Here, we considered non-trivial sites of carbon dioxide absorption and hydroxyamidine protonation, which, to our knowledge, have hardly been considered by other authors. Present DFT results agree rather well with the experimental data and support new insight into the formation of the PIL structure. Full article

In the context of fifth-generation (5G) communications and the dawn of sixth-generation (6G) networks, a surged societal demand on bandwidth and data rate and more stringent commercial requirements on transmission efficiency, cost, and reliability are increasingly evident and, hence, driving the maturity of reconfigurable millimeter-wave (mmW) and terahertz (THz) devices and systems, in particular, liquid crystal (LC)-based tunable solutions for delay line phase shifters (DLPSs). However, the field of LC-combined electronics has witnessed only incremental developments in the past decade. First, the tuning principle has largely been unchanged (leveraging the shape anisotropy of LC molecules in microscale and continuum mechanics in macroscale for variable polarizability). Second, LC-enabled devices’ performance has yet to be standardized (suboptimal case by case at different frequency domains). In this context, this work points out three underestimated knowledge gaps as drawn from our theoretical designs, computational simulations, and experimental prototypes, respectively. The first gap reports previously overlooked physical constraints from the analytical model of an LC-embedded coaxial DLPS. A new geometry-dielectric bound is identified. The second gap deals with the lack of consideration in the suboptimal dispersion behavior in differential delay time (DDT) and differential delay length (DDL) for LC phase-shifting devices. A new figure of merit (FoM) is proposed and defined at the V-band (60 GHz) to comprehensively evaluate the ratios of the DDT and DDL over their standard deviations across the 54 to 66 GHz spectrum. The third identified gap deals with the in-depth explanation of our recent experimental results and outlook for partial leakage attack analysis of LC phase shifters in modern eavesdropping. Full article

HDAC8 is a histone deacetylase enzyme that plays a key role in the development of various diseases in humans, including cancers, neurodegenerative diseases, and alcohol use disorder. Although HDAC8 is classified as a Zn²⁺-dependent metalloenzyme, available data regarding the affinity of other biologically relevant ions, such as Fe²⁺, Ni²⁺, Co²⁺, and Mg²⁺, for the HDAC8 enzyme active site remain unclear and contradictory. The mechanism by which these ions compete with Zn²⁺ for the HDAC8 active site is not well understood. In this study, we performed density functional theory (DFT) calculations at the B3LYP/6-31+G(d) level of theory, combined with polarizable continuum model computations (PCM) in water (ε = 78) and methanol (ε = 32). The results show that Zn²⁺ remains the thermodynamically preferred cofactor across all modeled reactions. Although Fe²⁺ and Co²⁺ gain partial stabilization upon increasing coordination number, the associated entropic and desolvation penalties prevent them from outcompeting Zn²⁺ under physiologically relevant conditions. Only a limited number of substitution reactions for Fe²⁺ and Co²⁺ yield ∆G values near thermodynamic neutrality, and only in specific coordination states. In contrast, all modeled Ni²⁺ substitution reactions are unfavorable, and Mg²⁺ is strongly excluded from the HDAC8 active site in all reactions. The resulting metal preference hierarchy—Zn²⁺ > Co²⁺ ≈ Fe²⁺ > Ni²⁺ > Mg²⁺—supports experimental observations and clarifies the intrinsic selectivity of the HDAC8 enzyme towards Zn²⁺. These insights provide a molecular basis for understanding HDAC8 metallo-regulation and may guide the rational design of novel, isoform-specific HDACi with improved binding properties. Full article

This study reports the synthesis and comprehensive spectroscopic characterization of 4-indolylcyanamide (4ICA), a novel indole-derived infrared (IR) probe designed for assessing local microenvironments in biological systems. 4ICA was synthesized via a two-step procedure with an overall yield of 43%, and its structure was confirmed using high-resolution mass spectrometry and ¹HNMR. Fourier Transform Infrared (FTIR) spectroscopy revealed that the cyanamide group stretching vibration of 4ICA exhibits exceptional solvent-dependent frequency shifts, significantly greater than those of conventional cyanoindole probes. A strong linear correlation was observed between the vibrational frequency and the combined Kamlet–Taft parameter, underscoring the dominant role of solvent polarizability and hydrogen bond acceptance in modulating its spectroscopic behavior. Quantum chemical calculations employing density functional theory (DFT) with a conductor-like polarizable continuum model (CPCM) provided further insight into the solvatochromic shifts and suppression of Fermi resonance in high-polarity solvents such as DMSO. Additionally, IR pump–probe measurements revealed short vibrational lifetimes (~1.35 ps in DMSO and ~1.13 ps in ethanol), indicative of efficient energy relaxation. With a transition dipole moment nearly twice that of traditional nitrile-based probes, 4ICA demonstrates enhanced sensitivity and signal intensity, establishing its potential as a powerful tool for site-specific environmental mapping in proteins and complex biological assemblies using nonlinear IR techniques. Full article

We report a computational investigation on the reachability of the molecular similarity index (MSI) approach for predicting the relative drug strength of methylcarbamate derivatives. Traditional MSI values have been obtained by calculating the overlap integral of total electron momentum densities between one molecule and another. Furthermore, we have proposed and tested orbital-specific MSI (OS-MSI) values, obtained by doing the same but with electron momentum densities of a selected molecular orbital (MO) such as the highest occupied MO (HOMO) and the lowest unoccupied MO (LUMO). In the calculations, a Boltzmann-weighted electron momentum density estimated by a theoretical probability distribution of rotamers was used, while the solvation effect was considered using the polarizable continuum model. It is shown that the traditional MSI values as well as the OS-MSI values for the HOMO do not have any correlation with experimental relative toxicity of the methylcarbamate derivatives. In contrast, it has been observed and found that the OS-MSI values for the LUMO exhibit a noticeable correlation with the experimental data. The reason behind this observation is discussed in relation to the drug reaction mechanism of the methylcarbamate derivatives. Full article

In this study, the influence of various implicit solvent models on the structural and thermodynamic properties of dacarbazine complexes with three cyclodextrins—α-CD, HP-β-CD, and HE-β-CD—was evaluated. The models considered were the polarizable continuum model (PCM), the conductor-like polarizable continuum model (CPCM), the solvation model based on density (SMD), and the Onsager model. Theoretical thermodynamic results were compared with experimental data obtained from conductometric studies. Our findings indicated that all three cyclodextrins form stable 1:1 inclusion complexes with dacarbazine. Among them, the complexes with HE-β-CD were the most thermodynamically stable. While the choice of solvent model had a minor impact on the structural properties of the complexes, it significantly affected thermodynamic parameters such as enthalpy, Gibbs free energy, and solvation free energy. The best agreement with experimental data—particularly for the Gibbs free energy of solvation—was observed when using the SMD model. Full article

Because of the involvement of π-electron cyclic constituents in their side chains, the so-called aromatic residues give rise to a number of strong, narrow, and well-resolved lines spread over the middle wavenumber (1800–600 cm⁻¹) region of the Raman spectra of peptides and proteins. The number of characteristic aromatic markers increases with the structural complexity (Phe → Tyr → Trp), herein referred to as (F_i = 1, …, 6) in Phe, (Y_i = 1, …, 7) in Tyr, and (W_i = 1, …, 8) in Trp. Herein, we undertake an overview of these markers through the analysis of a representative data base gathered from the most structurally simple tripeptides, Gly-Xxx-Gly (where Xxx = Phe, Tyr, Trp). In this framework, off-resonance Raman spectra obtained from the aqueous samples of these tripeptides were jointly used with the structural and vibrational data collected from the density functional theory (DFT) calculations using the M062X hybrid functional and 6-311++G(d,p) atomic basis set. The conformation dependence of aromatic Raman markers was explored upon a representative set of 75 conformers, having five different backbone secondary structures (i.e., β-strand, polyproline-II, helix, classic, and inverse γ-turn), and plausible side chain rotamers. The hydration effects were considered upon using both implicit (polarizable solvent continuum) and explicit (minimal number of 5–7 water molecules) models. Raman spectra were calculated through a multiconformational approach based on the thermal (Boltzmann) average of the spectra arising from all calculated conformers. A subsequent discussion highlights the conformational landscape of conformers and the wavenumber dispersion of aromatic Raman markers. In particular, a new interpretation was proposed for the characteristic Raman doublets arising from Tyr (~850–830 cm⁻¹) and Trp (~1360–1340 cm⁻¹), definitely excluding the previously suggested Fermi-resonance-based assignment of these markers through the consideration of the interactions between the aromatic side chain and its adjacent peptide bonds. Full article

We investigated the geometry and electronic structure of the oxygen-bridged dicopper complex [Cu^II₂(NH₃)₄O₂]²⁺ and discussed how different DFT methods and basis sets, including dispersion corrections and dielectric media, affect the predicted structure and spin state. Our results showed that pure functionals yielded the closed-shell singlet character, whereas hybrid functionals presented a partial diradical character that coincided with increased spin contamination. Incorporating a polarizable continuum model further enhanced the diradical character and more closely reproduced the measured Cu–Cu distance with a bent Cu₂O₂ core. Analysis of the molecular orbitals and computed absorption spectra revealed how orbitals produce the key transition from ligand-to-metal charge transfer. These findings underscore how environmental effects influence the description of Cu₂O₂ chemistry. Full article

Polarizable continuum methods (PCM) have been widely employed for simulating solvent effects, in spite of the fact that they either ignore specific interactions in solution or only partially reproduce non-specific contributions. Examples of three solvatochromic dyes with a negative, a positive and a reverse behavior illustrate the achievements and shortcomings of PCM calculations and the causes for their variable success. Even when qualitatively mimicking non-specific solvent effects, departures of calculated values from experimental data may be significant (20–30%). In addition, they can utterly fail to reproduce an inverted behavior that is caused by significant specific contributions by the solvent. As shown through a theoretical model that rationalizes and predicts the solvatochromism of phenolate merocyanines based on DFT (Density Functional Theory) descriptors in the gas phase, PCM shortcomings are to be held responsible for its eventual failure to reproduce experimental data in solution. Full article

The Coulomb coupling between transition densities of the pigments in photosynthetic pigment-protein complexes, termed excitonic coupling, is a key factor for the description of optical spectra and energy transfer. A challenging question is the quantification of the screening of the excitonic coupling by the optical polarizability of the environment. We use the equivalence between the sophisticated quantum chemical polarizable continuum (PCM) model and the simple electrostatic Poisson-TrEsp approach to analyze the distance and orientation dependence of the dielectric screening between chlorophylls in photosystem I trimers. On the basis of these calculations we find that the vacuum couplings $V_{mn}^{\left(0\right)}$ and the couplings in the dielectric medium $V_{mn}=f_{mn}{V}_{mn}^{\left(0\right)}$ are related by the empirical screening factor $f_{mn}=0.60+39.6\theta \left(\right|{\kappa }_{mn}|-1.17)exp(-0.56R_{mn}/\AA )$, where ${\kappa }_{mn}$ is the usual orientational factor of the dipole-dipole coupling between the pigments, $R_{mn}$ is the center-to-center distance, and the Heaviside-function $\theta \left(\right|{\kappa }_{mn}|-1.17)$ ensures that the exponential distance dependence only contributes for in-line type dipole geometries. We are confident that the present expression can be applied also to other pigment-protein complexes with chlorophyll or related pigments of similar shape. The variance between the Poisson-TrEsp and the approximate coupling values is found to decrease by a factor of 8 and 3–4 using the present expression, instead of an exponential distance dependent or constant screening factor, respectively, assumed previously in the literature. Full article

Utilizing Density Functional Theory (DFT) calculations at the B3LYP/QZVP level and incorporating the Conductor-like Polarizable Continuum Model (C-PCM) for solvation, the thermodynamic and chemical activity properties of 21-(hydroxymethoxy)henicosadecaenal, identified in cultured freshwater pearls from the mollusk Hyriopsis cumingii, have been elucidated. The study demonstrates that this compound releases formaldehyde, a potent antimicrobial agent, through dehydrogenation and deprotonation processes in both hydrophilic and lipophilic environments. Moreover, this polyenal exhibits strong anti-reductant properties, effectively scavenging free radicals. These critical properties classify the pearl-derived ingredient as a natural multi-functional compound, serving as a coloring, antiradical, and antimicrobial agent. The 2-(hydroxymethoxy)vinyl (HMV) moiety responsible for the formaldehyde release can be transferred to other compounds, thereby enhancing their biological activity. For instance, tyrosol (4-(2-hydroxyethyl)phenol) can be modified by substituting the less active 2-hydroxyethyl group with the active HMV one, and hinokitiol (4-isopropylotropolone) can be functionalized by attaching this moiety to the tropolone ring. A new type of meso-carrier, structurally modeled on pearls, with active substances loaded both in the layers and the mineral part, has been proposed. Full article

Carbonic anhydrases are mononuclear metalloenzymes catalyzing the reversible hydration of carbon dioxide in organisms belonging to all three domains of life. Although the mechanism of the catalytic reaction is similar, different families of carbonic anhydrases do not have a common ancestor nor do they exhibit significant resemblance in the amino acid sequence or the structure and composition of the metal-binding sites. Little is known about the physical principles determining the metal affinity and selectivity of the catalytic centers, and how well the native metal is protected from being dislodged by other metal species from the local environment. Here, we endeavor to shed light on these issues by studying (via a combination of density functional theory calculations and polarizable continuum model computations) the thermodynamic outcome of the competition between the native metal cation and its noncognate competitor in various metal-binding sites. Typical representatives of the competing cations from the cellular environments of the respective classes of carbonic anhydrases are considered. The calculations reveal how the Gibbs energy of the metal competition changes when varying the metal type, structure, composition, and solvent exposure of the active center. Physical principles governing metal competition in different carbonic anhydrase metal-binding sites are delineated. Full article

Previous theoretical investigations of the reactions between an OH radical and a nucleobase have stated the most important pathways to be the C5-C6 addition for pyrimidines and the C8 addition for purines. Furthermore, the abstraction of a methyl hydrogen from thymine has also been proven an important pathway. The conclusions were based solely on gas-phase calculations and harmonic vibrational frequencies. In this paper, we supplement the calculations by applying solvent corrections through the polarizable continuum model (PCM) solvent model and applying anharmonicity in order to determine the importance of anharmonicity and solvent effects. Density functional theory (DFT) at the $\omega$B97-D/6-311++G(2df,2pd) level with the Eckart tunneling correction is used. The total reaction rate constants are found to be 1.48 $\times {10}^{-13}$ cm³ molecules⁻¹s⁻¹ for adenine, 1.02 $\times {10}^{-11}$ cm³ molecules⁻¹s⁻¹ for guanine, 5.52 $\times {10}^{-13}$ cm³ molecules⁻¹s⁻¹ for thymine, 1.47 $\times {10}^{-13}$ cm³ molecules⁻¹s⁻¹ for cytosine and 7.59 $\times {10}^{-14}$ cm³ molecules⁻¹s⁻¹ for uracil. These rates are found to be approximately two orders of magnitude larger than experimental values. We find that the tendencies observed for preferred pathways for reactions calculated in a solvent are comparable to the preferred pathways for reactions calculated in gas phase. We conclude that applying a solvent has a larger impact on more parameters compared to the inclusion of anharmonicity. For some reactions the inclusion of anharmonicity has no effect, whereas for others it does impact the energetics. Full article

FTIR spectroscopy accompanied by quantum chemical simulations can reveal important information about molecular structure and intermolecular interactions in the condensed phase. Simulations typically account for the solvent either through cluster quantum mechanical (QM) models, polarizable continuum models (PCM), or hybrid quantum mechanical/molecular mechanical (QM/MM) models. Recently, we studied the effect of aqueous solvent interactions on the vibrational frequencies of lumiflavin, a minimal flavin model, using cluster QM and PCM models. Those models successfully reproduced the relative frequencies of four prominent stretching modes of flavin’s isoalloxazine ring in the diagnostic 1450–1750 cm⁻¹ range but poorly reproduced the relative band intensities. Here, we extend our studies on this system and account for solvation through a series of increasingly sophisticated models. Only by combining elements of QM clusters, QM/MM, and PCM approaches do we obtain an improved agreement with the experiment. The study sheds light more generally on factors that can impact the computed frequencies and intensities of IR bands in solution. Full article

The structure, energetics, and aromaticity of c.a. 100 constitutional isomers and tautomers of pyrido[m,n]diazepines (m = 1, 2; n = 2, 3, 4, 5; m ≠ n) were studied at the B3LYP/cc-pVTZ level. The pyrido[1,3]diazepines appear the most, while pyrido[2,4]diazepines are the least stable (ca. 26 kcal/mol). In the pyrido[1,n]diazepine group (n = 2–5), the [1,5] isomers are higher in energy by ca. 4.5 kcal/mol and the [1,4] ones by ca. 7 kcal/mol, and the pyrido[1,2]diazepines are the least stable (ca. 20 kcal/mol). All the most stable pyrido[1,n]diazepines have N-atoms near the ring’s junction bond but on opposite sites. The most stable [2,n]-forms are also those with the pyridine ring N6-atom near the junction bond. Surprisingly, for the [1,2]-, [1,3]-, and [1,4]-isomer condensation types of pyridine and diazepine rings, the same N9 > N7 > N6 > N8 stability pattern obeys. The stability remains similar in a water medium simulated with the Polarizable Continuum Model of the solvent and is conserved when calculated using the CAM-B3LYP or BHandHlyp functionals. The ring’s aromaticity in the pyridine[m,n]diazepines was established based on the integral INICS index resulting from the NICSzz-scan curves’ integration. The integral INICS index is physically justified through its relation to the ringcurrent as demonstrated by Berger, R.J.F., et al. Phys. Chem. Chem. Phys. 2022, 24, 624. The six-membered pyrido rings have negative INICS_ZZ indices and can be aromatic only if they are not protonated at the N-atom. All protonated pyrido and seven-membered rings exhibit meaningful positive INICS_ZZ values and can be assigned as antiaromatic. However, some non-protonated pyrido rings also have substantial positive INICS_ZZ indices and are antiaromatic. A weak linear correlation (R² = 0.72) between the INICS_ZZ values of the pyridine I(6) and diazepine I(7) rings exists and is a consequence of the communication between the π-electron systems of the two rings. The juxtaposition of the INICS descriptor of the six- and seven-membered rings and diverse electron density parameters at the Ring Critical Points (RCP) revealed good correlations only with the Electrostatic Potentials from the electrons and nuclei (ESPe and ESPn). The relationships with other RCP parameters like electron density and its Laplacian, total energy, and the Hamiltonian form of kinetic energy density were split into two parts: one nearly constant for the six-membered rings and one linearly correlating for the seven-membered rings. Thus, most of the electron density parameters at the RCP of the six-membered rings of pyridodiazepines practically do not change with the diazepine type and the labile proton position. In contrast, those of the seven-membered rings display aromaticity changes in the antiaromatic diazepine with its ring structural modifications. Full article