Molecular Environment Modulates CO2 Liberation from Carboxy-Biotin.

Carboxy-biotin serves as a coenzyme in certain carboxylases, exhibiting the remarkable capability to transfer a carboxy group to specific substrates. This process is made possible by the presence of biotin, a unique molecule that consists of a sulfur-containing tetrahydrothiophene ring fused to a ureido group. It is covalently attached to the enzyme via a flexible linker, allowing for its functionality. Biotin-dependent carboxylases consist of two distinct domains. The first domain (BC) facilitates biotin carboxylation by utilizing ATP, while the second domain (CT) transfers CO2 to the substrate. The process of ATP-dependent carboxylation using bicarbonate in the biotin carboxylase domain (BC) is well-known. However, the precise mechanism by which CO2 is released in the carboxyltransferase domain (CT) is still not fully understood. We employed advanced computational chemistry methods to investigate the decarboxylation process of carboxy-biotin in various molecular environments and different protonation states. Regardless of the polarity of the molecular surroundings, decarboxylation only occurs spontaneously in the protonated form. To determine the protonation state of biotin in different environments, we established an accurate computational chemistry method for calculating the pKa value of carboxy-biotin, reaching sub-kcal/mol accuracy. Based on our findings, nonpolar environments, such as the active site of the carboxyltransferase domain, have the ability to cause the spontaneous release of CO2 from carboxy-biotin. The CO2 release takes place spontaneously from protonated carboxy-biotin, promoting the carboxylation of substrates.

Multicomponent synthesis and photophysical study of novel α,ß-unsaturated carbonyl depsipeptides and peptoids.

Multicomponent reactions were performed to develop novel α,ß-unsaturated carbonyl depsipeptides and peptoids incorporating various chromophores such as cinnamic, coumarin, and quinolines. Thus, through the Passerini and Ugi multicomponent reactions (P-3CR and U-4CR), we obtained thirteen depsipeptides and peptoids in moderate to high yield following the established protocol and fundamentally varying the electron-rich carboxylic acid as reactants. UV/Vis spectroscopy was utilized to study the photophysical properties of the newly synthesized compounds. Differences between the carbonyl-substituted chromophores cause differences in electron delocalization that can be captured in the spectra. The near UV regions of all the compounds exhibited strong absorption bands. Compounds P2, P5, U2, U5, and U7 displayed absorption bands in the range of 250-350 nm, absorbing radiation in this broad region of the electromagnetic spectrum. A photostability study for U5 showed that its molecular structure does not change after exposure to UV radiation. Fluorescence analysis showed an incipient emission of U5, while U6 showed blue fluorescence under UV radiation. The photophysical properties and electronic structure were also determined by TD-DFT theoretical study.

Comparative Study of the Removal Efficiency of Nalidixic Acid by Poly[(4-vinylbenzyl)trimethylammonium Chloride] and N-Alkylated Chitosan through the Ultrafiltration Technique and Its Approximation through Theoretical Calculations.

Emerging antibiotic contaminants in water is a global problem because bacterial strains resistant to these antibiotics arise, risking human health. This study describes the use of poly[(4-vinylbenzyl) trimethylammonium chloride] and N-alkylated chitosan, two cationic polymers with different natures and structures to remove nalidixic acid. Both contain ammonium salt as a functional group. One of them is a synthetic polymer, and the other is a modified artificial polymer. The removal of the antibiotic was investigated under various experimental conditions (pH, ionic strength, and antibiotic concentration) using the technique of liquid-phase polymer-based retention (LPR). In addition, a stochastic algorithm provided by Fukui's functions is used. It was shown that alkylated N-chitosan presents 65.0% removal at pH 7, while poly[(4-vinylbenzyl)trimethylammonium chloride] removes 75.0% at pH 9. The interaction mechanisms that predominate the removal processes are electrostatic interactions, π-π interactions, and hydrogen bonding. The polymers reached maximum retention capacities of 1605 mg g-1 for poly[(4-vinylbenzyl) trimethylammonium chloride] and 561 mg g-1 of antibiotic per gram for alkylated poly(N-chitosan). In conclusion, the presence of aromatic groups improves the capacity and polymer-antibiotic interactions.

Formation and evolution of C-C, C-O, C[double bond, length as m-dash]O and C-N bonds in chemical reactions of prebiotic interest.

A series of prebiotic chemical reactions yielding the precursor building blocks of amino acids, proteins and carbohydrates, starting solely from HCN and water is studied here. We closely follow the formation and evolution of the pivotal C-C, C-O, C[double bond, length as m-dash]O, and C-N bonds, which dictate the chemistry of the molecules of life. In many cases, formation of these bonds is set in motion by proton transfers in which individual water molecules act as catalysts so that water atoms end up in the products. Our results indicate that the prebiotic formation of carbon dioxide, formaldehyde, formic acid, formaldimine, glycolaldehyde, glycine, glycolonitrile, and oxazole derivatives, among others, are best described as highly nonsynchronous concerted single step processes. Nonetheless, for all reactions involving double proton transfer, the formation and breaking of O-H bonds around a particular O atom occur in a synchronous fashion, apparently independently from other primitive processes. For the most part, the first process to initiate seems to be the double proton transfer in the reactions where they are present, then bond breaking/formation around the reactive carbon in the carbonyl group and finally rupture of the C-N bonds in the appropriate cases, which are the most reluctant to break. Remarkably, within the limitations of our non-dynamical computational model, the wide ranges of temperature and pressure in which these reactions occur, downplay the problematic determination of the exact constraints on the early Earth.

Structural Requirements of N-alpha-Mercaptoacetyl Dipeptide (NAMdP) Inhibitors of Pseudomonas Aeruginosa Virulence Factor LasB: 3D-QSAR, Molecular Docking, and Interaction Fingerprint Studies.

The zinc metallopeptidase Pseudomonas elastase (LasB) is a virulence factor of Pseudomonas aeruginosa (P. aeruginosa), a pathogenic bacterium that can cause nosocomial infections. The present study relates the structural analysis of 118 N-alpha-mercaptoacetyl dipeptides (NAMdPs) as LasB inhibitors. Field-based 3D-QSAR and molecular docking methods were employed to describe the essential interactions between NAMdPs and LasB binding sites, and the chemical features that determine their differential activities. We report a predictive 3D-QSAR model that was developed according to the internal and external validation tests. The best model, including steric, electrostatic, hydrogen bond donor, hydrogen bond acceptor, and hydrophobic fields, was found to depict a three-dimensional map with the local positive and negative effects of these chemotypes on the LasB inhibitory activities. Furthermore, molecular docking experiments yielded bioactive conformations of NAMdPs inside the LasB binding site. The series of NAMdPs adopted a similar orientation with respect to phosphoramidon within the LasB binding site (crystallographic reference), where the backbone atoms of NAMdPs are hydrogen-bonded to the LasB residues N112, A113, and R198, similarly to phosphoramidon. Our study also included a deep description of the residues involved in the protein-ligand interaction patterns for the whole set of NAMdPs, through the use of interaction fingerprints (IFPs).

Studying the phosphoryl transfer mechanism of the E. coli phosphofructokinase-2: from X-ray structure to quantum mechanics/molecular mechanics simulations.

Phosphofructokinases (Pfks) catalyze the ATP-dependent phosphorylation of fructose-6-phosphate (F6P) and they are regulated in a wide variety of organisms. Although numerous aspects of the kinetics and regulation have been characterized for Pfks, the knowledge about the mechanism of the phosphoryl transfer reaction and the transition state lags behind. In this work, we describe the X-ray crystal structure of the homodimeric Pfk-2 from E. coli, which contains products in one site and reactants in the other, as well as an additional ATP molecule in the inhibitory allosteric site adjacent to the reactants. This complex was previously predicted when studying the kinetic mechanism of ATP inhibition. After removing the allosteric ATP, molecular dynamic (MD) simulations revealed conformational changes related to domain packing, as well as stable interactions of Lys27 and Asp256 with donor (ATP) and acceptor (fructose-6-) groups, and of Asp166 with Mg2+. The phosphoryl transfer reaction mechanism catalyzed by Pfk-2 was investigated through Quantum Mechanics/Molecular Mechanics (QM/MM) simulations using a combination of the string method and a path-collective variable for the exploration of its free energy surface. The calculated activation free energies showed that a dissociative mechanism, occurring with a metaphosphate intermediate formation followed by a proton transfer to Asp256, is more favorable than an associative one. The structural analysis reveals the role of Asp256 acting as a catalytic base and Lys27 stabilizing the transition state of the dissociative mechanism.

Understanding the nature of bonding interactions in the carbonic acid dimers.

Carbonic acid dimer, (CA)2, (H2CO3)2, helps to explain the existence of this acid as a stable species, different to a simple sum between carbon dioxide and water. Five distinct, well characterized types of intermolecular interactions contribute to the stabilization of the dimers, namely, C=O⋯H-O, H-O⋯H-O, C=O⋯C=O, C=O⋯O-H, and C-O⋯O-H. In many cases, the stabilizing hydrogen bonds are of at least the same strength as in the water dimer. We dissect the nature of intermolecular interactions and assess their influence on stability. For a set of 40 (H2CO3)2 isomers, C=O⋯H-O hydrogen bonds between the carbonyl oxygen in one CA molecule and the acidic hydrogen in the hydroxyl group at a second CA molecule are the major stabilizing factors because they exhibit the shortest interaction distances, the largest orbital interaction energies, and the largest accumulation of electron densities around the corresponding bond critical points. In most cases, these are closed-shell hydrogen bonds, however, in a few instances, some covalent character is induced. Bifurcated hydrogen bonds are a common occurrence in the dimers of carbonic acid, resulting in a complex picture with multiple orbital interactions of various strengths. Two anti-anti monomers interacting via the strongest C=O⋯H-O hydrogen bonds are the ingredients for the formation of the lowest energy dimers. Graphical Abstract Carbonic acid dimer, (CA)2, (H2CO3)2, helps explaining the existence of this acid as a stable species, different to a simple sum between carbon dioxide and water. Five distinct, well-characterized types of intermolecular interactions contribute to the stabilization of the dimers, namely, C=O⋯H-O, H-O⋯O-H, C=O⋯C=O, C=O⋯O-C, and C-O⋯O-C. In many cases, the stabilizing hydrogen bonds are of at least the same strength as in the water dimer.

Insights into bonding interactions and excitation energies of 3d-4f mixed lanthanide transition metal macrocyclic complexes.

In this contribution, a computational study of equatorial bound tetranuclear macrocycle (butylene linked) [LnZn(HOMBu)]3+ (Ln = La3+, Ce3+) complexes was carried out. Here, the electronic structure, bonding interaction and excitation energies were studied within the relativistic density functional theory framework. From the electronic structure analysis, the frontier molecular orbitals (FMOs) were strongly localized in the d-orbitals of the Zn centers and the f-orbitals of the lanthanide ions. Besides, the inner MOs were found to exhibit a π-character from the organic part of the macrocyclic chain. EDA-NOCV was used as a tool for evaluating the bonding interaction, taking the trinuclear metallomacrocycle (ZnHOMBu) and the lanthanide center as fragments. This analysis showed that the interaction between these fragments was slightly covalent; with this covalency being the result of a charge transfer from the metallomacrocyclic ring to the lanthanide. This phenomenon was observed in the deformation density channels obtained from the EDA-NOCV study; in which π- and σ-charge transfer was observed. Finally, the TD-DFT study of the excitation energies evidenced three sets of bands: the first set with the highest intensity represented the ligand to metal charge transfer bands; the second set could be attributed to the 3d-4f electronic transitions between the metal centers; and the third set represented the f-f bands found for the open-shell cerium complex. This class of complexes accomplishes the "antenna effect" principle, which states that highly absorptive transition-metal (TM) complexes can be used to enhance the luminescence of poorly emissive systems, and are introduced in this study as self-sensitizer bimetallic d-f systems with potential applications in near infra-red (NIR) technologies.

Aromatic Lateral Substituents Influence the Excitation Energies of Hexaaza Lanthanide Macrocyclic Complexes: A Wave Function Theory and Density Functional Study.

The high interest in lanthanide chemistry, and particularly in their luminescence, has been encouraged by the need of understanding the lanthanide chemical coordination and how the design of new luminescent materials can be affected by this. This work is focused on the understanding of the electronic structure, bonding nature, and optical properties of a set of lanthanide hexaaza macrocyclic complexes, which can lead to potential optical applications. Here we found that the DFT ground state of the open-shell complexes are mainly characterized by the manifold of low lying f states, having small HOMO-LUMO energy gaps. The results obtained from the wave function theory calculations (SO-RASSI) put on evidence the multiconfigurational character of their ground state and it is observed that the large spin-orbit coupling and the weak crystal field produce a strong mix of the ground and the excited states. The electron localization function (ELF) and the energy decomposition analysis (EDA) support the idea of a dative interaction between the macrocyclic ligand and the lanthanide center for all the studied systems; noting that, this interaction has a covalent character, where the d-orbital participation is evidenced from NBO analysis, leaving the f shell completely noninteracting in the chemical bonding. From the optical part we observed in all cases the characteristic intraligand (IL) (π-π*) and ligand to metal charge-transfer (LMCT) bands that are present in the ultraviolet and visible regions, and for the open-shell complexes we found the inherent f-f electronic transitions on the visible and near-infrared region.

Exploring the nature of the excitation energies in [Re6(µ3-Q8)X6](4-) clusters: a relativistic approach.

This contribution is a relativistic theoretical study to characterize systematically the main electronic transitions in a series of hexarhenium chalcogenide [Re6(µ3-Q8)X6](4-) clusters with the aim of understanding: (i) the terminal ligand substitution effect, (ii) the substitution effect of the chalcogenide ion on the [Re6(µ3-Q8)](2+)core, and finally (iii) the significance of the spin-orbit coupling (SOC) effect on the optical selection rules. In all the cases, we found characteristic bands at around 300-550 nm, where the band positions are directly determined by the terminal ligand. However, SCN(-)/NCS(-) presents a different nature of the orbitals involved in the electronic transitions, in comparison with the other studied terminal ligands, located in the near-infrared (NIR) region. All the bands are red-shifted as a consequence of the ligand contribution in the composition of the orbitals involved in the electronic excitations.

Understanding the influence of terminal ligands on the electronic structure and bonding nature in [Re6(µ3-Q8)](2+) clusters.

Since the synthesis of the first molecular cluster [Re6(µ3-Q8)X6](4-), the substitutional lability of the terminal ligands prompted new developments in their chemistry, making these molecular clusters a reasonable point of departure for building new materials. The development of novel inorganic materials of technological interest certainly requires an understanding of the electronic structure, bonding, spectroscopy, photophysical and structural properties of these clusters. Taking into account the potential applications in material sciences and the lack of systematization in the study of these kinds of clusters, the proposal of the present work is to perform a detailed theoretical study of the [Re6(µ3-Q8)X6](4-) (Q = S(2-), Se(2-), Te(2-); X = F(-), Cl(-), Br(-), I(-), CN(-), NC(-), SCN(-), NCS(-), OCN(-), NCO(-)) clusters based on the detailed description of the electronic structure of these complexes and the bonding nature between the [Re6(µ3-Q8)](2+) core and several donor-acceptor peripheral ligands. All this work was developed on the framework of the relativistic density functional theory, in which relativistic effects were incorporated by means of a two-component Hamiltonian with the zeroth-order regular approximation. To describe the relative stability of these complexes, we employed the global descriptors of chemical hardness and softness introduced by Pearson. Moreover, an analysis of bonding energetics was performed by combining a fragment approach to the molecular structure with the decomposition of the total bonding energy according to the Morokuma-Ziegler energy partitioning scheme. After an analysis of these results, we found in all cases an extensive ionic character in the bonding between the core and each peripheral ligand. The interaction between the halide ligand and the core gives about 75% ionic character, whereas the other ligands show a more covalent interaction due to effective synergic mechanisms. We conclude that the most stable clusters are those that present the stronger σ-donor terminal ligands, whereas the cluster stability starts to decrease when the π-acceptor effect will be stronger; this fact is directly related to the terminal ligand lability and the strong electrophilic character of the [Re6(µ3-Q8)](2+) core.

Electron transfer from the benzophenone triplet excited state directs the photochemical synthesis of gold nanoparticles.

The rarely recognized electron donating ability of the benzophenone triplet excited state provides an unusual route for the photochemical synthesis of gold nanoparticles.

Antenna effect by organometallic chromophores in bimetallic d-f complexes.

The nature of the intermetallic bond in a series of complexes of the type [Cp2-TM-M-Cp2] (where TM = Re and M = Y, La, Lu, Yb, Ac; also TM = Os and M = Th; Cp = cyclopentadienyl ligand) have been studied by relativistic two-component density functional theory (DFT) calculations. The results obtained in this work show that the interaction between the transition metal and lanthanide atoms is mainly ionic in all cases, while for the case of actinide atoms this interaction becomes significantly more covalent. The effective direction of the electron transfer between the Re→Ac or Os→Th centers allows us to propose that the [Cp2ReAcCp2] and [Cp2OsThCp2] complexes are ideal candidates for near-infrared (NIR) technologies since their absorption spectra show some transitions over 600 nm. We also observed a shifting of the absorption spectrum of around 100 nm of the [Cp2Re] fragment when is compared against the absorption spectrum of the entire complex. This behavior allows us to argue that the [Cp2Re] fragment is a good antenna chromophore due to the possibility of charge transfer transitions from this fragment to the f shell in lanthanide or actinide elements studied here.

Bonding nature and electron delocalization of An(COT)2, An = Th, Pa, U.

A systematic study of a series of An(COT)(2) compounds, where An = Th, Pa, U, and COT represents cyclooctatetraene, has been performed using relativistic density functional theory. The ZORA Hamiltonian was applied for the inclusion of relativistic effects, taking into account all of the electrons for the optimization and explicitly including spin-orbit coupling effects. Time-dependent density functional theory (TDDFT) was used to calculate the excitation energies with the GGA SAOP functional, and the electronic transitions were analyzed using double group irreducible representations. The calculated excitation energies are in perfect correlation with the increment of the ring delocalization as it increases along the actinide series. These results are sufficient to ensure that, for these complexes, the increment in delocalization, as indicated by ELF bifurcation and NICS analysis, leads to a shift in the maximum wavelength of absorption in the visible region. Also, delocalization in the COT ring increases along the actinide series, so the systems become more aromatic because of a modulation induced by the actinides.