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Recently, structural elucidation of natural products has undergone a revolution. The combined use of different modern spectroscopic methods has allowed obtaining a complete structural assignment of natural products using small amounts of sample. However, despite the extraordinary ongoing advances in spectroscopy, the mischaracterization of natural products has been and remains a recurrent problem, especially when the substance presents several stereogenic centers. The misinterpretation of NMR data has resulted in frequent reports addressing structural reassignment. In this context, a great effort has been devoted to developing quantum chemical calculations that simulate NMR parameters accurately, allowing to achieve a more precise spectral interpretation. In this work, we employed a protocol for theoretical calculations of 1 H NMR chemical shifts and coupling constants using DFT, followed by the application of the DP4+ method to revisit the structure of Heliannuol L, a member of the Heliannuol class, isolated from Helianthus annuus. Our results indicate that the originally proposed structure of Heliannuol L needs a stereochemical reassignment, placing the hydroxyl bonded to C10 in the opposite side of the methyl and hydroxyl groups bonded to C7 and C8, respectively.

The conversion of CO2 into dimethyl carbonate (DMC) is an environmental and industrial appealing topic because it contributes to reduce the emissions of CO2 and to increase its use as raw material. In the present study we employed the CAM-B3LYP/def2-SVP DFT approach to evaluate the thermodynamic and kinetic parameters for the catalytic conversion of CO2 and methanol into DMC. Starting with the activation of four methanol molecules by the [Me2SnO]2 dimer, we computed all the stationary points along the pathway to convert CO2 and methanol into the DMC. The capture of two CO2 molecules is promoted by an alkoxitin intermediate, in an exothermic process, with low activation energy. Formation of a first DMC occurs after an intramolecular rerrangement involving a tetrahedral intermediate. The formation of a second DMC may occur either in a process similar to the first one or by dimerization of the hemicarbonate formed after releasing the first DMC. In this pathway, the [Me2(OH)SnO(OMe)SnMe2]2 complex is formed. This complex is less reactive than [Me2Sn(OMe)2]2 but still conserves the catalytic activity. Identification of this mechanism suggests that the catalytic action of Me2SnO can be improved by modulating the formation of the final [Me2(OH)SnO(OMe)SnMe2]2 complex.

The structure and substitution energies of dichlorotris(triphenylphosphine)ruthenium(II) complex, [RuCl2(PPh3)3], was computed with ten different methods at the density functional theory level usin...

A stereoselective, base-free Heck coupling between 1,4-naphthoquinone and 1H-1,2,3-triazole derivatives was reported for the first time. This study shows that depending on the 1,4-naphthoquinone, the use of an additional base is unnecessary to produce the naphthoquinone-triazole conjugates. This is also the first example of a Heck coupling of these two cores without using a base as an additive. In this work, sixteen new naphthoquinone-triazole hybrids were stereoselectively synthetized in good to excellent yields. The reaction mechanism was discussed based on DFT CAM−B3LYP calculations. The first step is the coordination of the arene to the palladium catalyst to form a palladacycle intermediate. After reorganization in this intermediate, the double bond in the arene is restored to proceed with the coupling step and formation of the C−C bond in the rate determining step. The Kozuchi-Shaik span model was employed to rationalize substituent effects.

In the early 2000s, the first articles regarding the calculation of NMR parameters for natural products appeared in the literature. Since then, modelling 1H and 13C chemical shifts and spin–spin coupling constants for this class of compounds has experienced a remarkable increase in precision, accessibility, and application, leading to considerable advances in the field. More recently, significant contributions from several authors have led to continuous growth in this research field, updating and broadening the simulation of NMR parameters, in particular with the application of new techniques for data treatment. Nowadays, such studies are routinely found in the high impact literature. In this review, we intend to cover the general guidelines and the main advances in NMR calculations of natural products published since 2012. We intend to address the bottlenecks of quantum chemical calculations of NMR parameters, including mathematical definitions, updates, and a discussion of relevant examples, and to highlight novel tools, for example DU8+, CP3, DP4, DP4+ and J-DP4. We will cover all aspects of NMR simulation focusing on natural products, from the fundamentals to the new computational toolboxes available, combining advanced quantum chemical calculations with complex upstream data processing and machine learning.

The regioselective formation of α- and β-lapachone via hetero-Diels–Alder reactions was investigated by experimental and computational approaches. The experimentally observed α-selectivity was explored in detail, revealing that the lower energy barrier for the formation of α-lapachone is a result of lower Pauli repulsion throughout the reaction path, when compared to the β-isomer. By comparing equivalent points on both α- and β-lapachone potential energy surfaces (PES), according to the activation strain model (ASM) and energy decomposition analysis (EDA), we were able to demonstrate that the Pauli repulsion term increases more significantly when going from reactants to TSβ than to TSα, resulting in lower interaction energy in the early stages of the reaction path and in a later transition state for β-lapachone. Moreover, we confirmed that regio- and diastereoselectivity trends previously reported for other quinone methide intermediates are also observed for 3-methylene-1,2,4-naphthotriones, such as small endo/exo diastereoselectivity, as well as pronounced ortho/meta regioselectivity for reactions performed with dienophile containing electron-releasing groups. The results presented here provide a deeper understanding of the reactivity of quinone methide derivatives, aiding the future rational design of the reaction condition, structural modification of possible quinone methide intermediates, and the development of more selective synthetic routes for quinone derivatives.

To investigate the herbicidal potential of 2,5-diketopiperazines (2,5-DKPs), we applied a known protocol to produce a series of 2,5-DKPs through intramolecular

Nonlinear optical materials have been investigated recently due to their potential technological applications in information storage and communications. In this context, semi-organic crystals can effectively combine the desired nonlinear optical properties of amino acids with the promising mechanical and thermal properties of inorganic materials. In this work, we have synthesized and characterized a semi-organic crystal of the amino acid l-histidine and hydrofluoric acid and investigated the chemical interactions between the organic and inorganic moieties. The crystal of l-histidine bis(fluoride) has been produced by slow solvent evaporation and characterized by X-ray diffraction (XRD) crystallography and thermogravimetric and differential thermal analyses. The XRD conducted using the Rietveld method shows that the unit cell is orthorhombic with the P21212 space group and contains four l-histidine bis(fluoride) units. Both differential thermal analysis and temperature-dependent XRD show that the crystals are thermally stable up to 191°C and do not undergo phase transition. The computational Hirshfeld surface analysis of the crystal structure reveals the main intermolecular interactions. Density functional theory has been employed to calculate the ionic interaction energy and electrostatic potential maps and confirm the spontaneity of ionic association at 191°C. The combined experimental and computational results show that the thermal stability of the semi-organic l-histidine bis(fluoride) crystal makes it suitable for nonlinear optical applications in optical sensing and communication systems. Graphical abstract

Polymerization reactions using renewable raw material as substrate (namely, δ-valerolactone) and N-heterocyclic carbenes (NHC) as organocatalysts to form polyesters were investigated by computational approaches. Two routes were investigated for the reaction, either with the NHC acting as a Bronsted base and activating an alcohol used as co-initiator or by direct nucleophilic attack of the NHC on the carbonyl carbon of the lactone, forming a zwitterionic intermediate. In agreement with previous studies, the lowest energy pathway leading to polymerization is that where the NHC activates the alcohol co-initiator, yielding a partially charged alkoxide that then performs a nucleophilic attack on the lactone. The proton affinity of the NHCs shows a high correlation with the activation enthalpy for the first reaction step. Thus, NHCs with high proton affinity stabilize the first intermediate and make the lactone ring-opening the rate-determining step for the reaction.

In this work, we present the dielectric behavior of water with a novel flexible model, FAB/ $$\epsilon $$ , that improved three-site water models. Different concentrations of the ionic liquid 1-butyl-3-methylimidazolium [bmim] and bis(trifluoromethanesulfonyl)imide [ $$\hbox {Tf}_2$$ N] with water have been investigated. The study was performed by molecular dynamics simulations using three water models, being two non-polarizable 3-site SPC/E and SPC/e and a flexible 3-site FAB/ $$\epsilon $$ model. Systematic thermodynamics and dynamical and dielectric properties were investigated, such as density, self-diffusion coefficient, heat of vaporization $$\Delta H_\mathrm{vap}$$ , and surface tension at 300 K and 1 bar. Extrapolating the experimental molar fraction of the mixtures, a pattern change for all properties was observed, evidencing the phase separation previously reported by experimental data. The results also show the dielectric effect in the system, which is important in ionic systems and fundamental for understanding why this ionic liquid behaves hydrophobic.

The skeleton of the helianane's family is an unsolved controversial topic. Recent synthetic studies and 13C NMR structural analysis have demanded for an amendment of helianane to the open ring curcudiol. However, some authors argue that the original helianane structure, a benzofused eight-membered ether ring system, cannot be ruled out immediately without further spectral analyses of curcudiol and helianane. The fact that this compound is extremely rare, obtained only from marine organisms, makes remote the possibility of reisolation. Therefore, we decided to approach this problem computationally. Herein, we performed a complementary quantum mechanical study in order to provide more information about the helianane's actual skeleton. Our 13C NMR chemical shifts calculations suggests that the curcudiol structure is more likely to be the correct one. In addition, we simulated the formation pathways for both products starting from the known biosynthetic precursor. The results show that curcudiol is around 8.0 kcal mol−1 more stable than the originally proposed helianane structure.

In this work we present the dielectric behavior of water with a novel flexible model that improved all three sites water models Different concentrations of the ionic liquid 1-butyl-3-methylimidazolium [bmim] bis(trifluoromethanesulfonyl)imide [Tf2N] with water was investigated. The study was performed by molecular dynamics simulations using three water models, being two non-polarizable 3-site SPC/E and SPC/e, and a novel flexible 3-site FAB/ model. Systematic thermodynamics, dynamical and dielectric properties were investigated, such as density, diffusion coefficient, heat of vaporization ∆Hvap, and surface tension at 300 K and 1 bar. We extrapolated the experimental molar fraction of the mixtures and a pattern change for all properties was observed, evidencing the phase separation previously reported by experimental data. The results also display the dielectric effect of the system on the calculated properties.

4-quinolones derivatives can present fluorescent properties, depending on their substituents and on the chemical environment (e.g., acidic medium), allowing their application as ion sensors. We theoretically evaluated the photophysical properties of previously synthesized 3-acyl-4-quinolones to verify how different substituents (R1=H, NH2 and R2 = OEt, OH, NHPh) affect their absorption profiles and the emission profile of a reference compound, PB3. All DFT and TD-DFT calculations were performed at B3LYP-D3/6-311++G(d,p) level and continuum polarization model for simulated acetonitrile as solvent. For PB2 (R1 = H, R2 = OEt), we observed hypsochromic shift compared to PB3 due to the increase of the gap between HOMO/LUMO (absence of electron-donating group), in accordance with experimental data. For R1=NH2 and R2=OH, NHPh (PB6 and PB10, respectively), the gap between HOMO/LUMO increases, resulting in a soft bathochromic shift for the simulated absorption spectra. In addition, we evaluated the effect of acid addition on the absorption and emission profile of PB3 and the results were compared with experimental data. Our thermodynamic results suggest that protonation occurs on the endocyclic carbonyl of the quinolone moiety, probably due to an increased aromatic character, as suggested by our NICS calculations. Finally, we associate the increase of the fluorescence in the acidic medium to the establishment of an intramolecular hydrogen bond and, thus, increased rigidity.

In the past, structure determination of natural products was an arduous process depending almost entirely on chemical synthesis, mainly by derivatization and degradation processes, taking years of effort. Recently, structural elucidation of natural products has undergone a revolution. Nowadays, with the combined use of different advanced spectroscopic methods, it became possible to completely assign the structure of natural products using small amounts of sample. However, despite the extraordinary ongoing advances in spectroscopy, the mischaracterization of natural products has been and remains a recurrent problem, especially in the presence of several chiral centers. The misinterpretation of NMR data has resulted in frequent reports addressing the issue of structural reassignment. In this context, a great effort has been devoted to the development of quantum chemical calculations to predict NMR parameters, and thus achieve a more accurate spectral interpretation. In this work, we applied a protocol for theoretical calculations of 1H NMR chemical shifts in order to establish the correct and unequivocal structure of Helianuol L, a member of the Heliannuol’s class, isolated from Helianthus annus. These secondary metabolites present a broad spectrum of biological activities, including the allelochemical activity, making them promising candidates as natural agrochemicals. It is worth mentioning, however, that the process of elucidating the structure of Heliannuol L was based on structural correlations with molecules already known in the literature, where few stereochemical analyses were performed. In this way, based on the fact that other compounds of the Heliannuol’s class had their structure previously reassigned, the verification of the proposed structure of Heliannuol L becomes of great importance.

The properties of natural products, including their biological and pharmacological activities, are directly correlated with their chemical structures. Thus, a correct structural characterization of these compounds is a crucial step to the understanding of their biological activities. However, despite the recent advances in spectroscopic techniques, structural studies of natural products can be challenging. This way, theoretical calculations of Nuclear Magnetic Resonance (NMR) parameters (such as chemical shifts and coupling constants) have proven to be a powerful and low-cost tool for the aid to experimental techniques traditionally used for the structural characterization of natural products. One of the several applications of quantum-mechanical calculations of NMR parameters is the study of tautomerism. Since chemical shifts are sensitive to the tautomeric equilibrium, this technique can provide crucial informations. In this work, it was applied a protocol for theoretical calculations of ¹³C chemical shifts in order to study the tautomerism of the natural product 7-epi-clusianone, isolated from Rheedia gardneriana. This protocol consists in a Monte Carlo conformational search, followed by geometry optimization and shielding tensors calculations, both using a density functional level of theory. After comparison of theoretical and experimental data, it was possible to confirm the two tautomers present in equilibrium in the experimental solution. Furthermore, this study highlights how this theoretical protocol can be an effective method in identifying the preferred tautomeric form in solution.

Three molecules containing morpholine, 1,4-naphthoquinone, 7-chloroquinoline and 1,3,5-triazine cores, scaffolds with recognized anti-corrosive activity, were synthesized and had their anticorrosive activity evaluated through potentiodynamic polarization and electrochemical impedance studies. Both studies were conducted in a simulated production water medium containing 150,000 mg·L-1 Cl- and 5 mg·L-1 S2-. Corrosion inhibition efficiency ranged from 67% - 86%, amongst which the naphthoquinone-containing derivative (compound 1) was the most effective. These compounds act through formation of a protective film on the surface of AISI 316 stainless steel. Investigation of the molecular properties of the prepared inhibitors by DFT calculations revealed that the LUMO energy and chemical hardness of the molecules can be directly correlated with their inhibition efficiency.

This work describes the first determination of the absolute configuration (AC) of (−)-cubebin by means of electronic circular dichroism (ECD), supported by quantum chemical calculations. The comparison of experimental ECD with the corresponding quantum chemical prediction for the proper diastereoisomer resulted in the definitive assignment of the AC of the naturally occurring (−)-cubebin as (8R,8aR,9S). The challenging determination of the relative configuration (RC) of cubebin based only on experimental nuclear magnetic resonance (NMR) methods is stressed. Computation of the 13C and 1H NMR chemical shifts for all the possible diastereoisomers leads to values of mean absolute error and root mean square deviation that do not allow distinguishing among them. Thus, errors in stereochemical determination can easily occur even when using two-dimensional methods, which clearly demonstrate the complexity of this special case. To determine the RC of this bioactive natural compound with high level of confidence, it was necessary to combine the DP4+ method with X-ray crystallography. Therefore, employing the commonly used empirical methods to determine the AC of (−)-cubebin can easily lead to misassignment of its stereochemistry.

The emission of carbon dioxide in large amounts is commonly believed to be the main cause of global climate changes. Development of CO2 capture processes is still a big current challenge. Some anions have been studied for the gas sequestration process due their great affinity to CO2. In this work, electronic structure calculations were performed at the MP2/aug-cc-pvtz level to compute the interaction between 20 anions and CO2. A CBS scheme, using extrapolated energies, was also employed for both gas phase and solvent calculations. The reactions between the anions and CO2 were therefore studied in four different conditions (gas phase, toluene, tetrahydrofuran and water). The trends observed for the reaction thermodynamics with the MP2 method is similar to that observed previously with the B3LYP-D3 and M06-2X functionals. The reactions in the gas phase are highly exothermic and do not involve any activation energy. The solvent effect reduces the exothermicity and induces an intrinsic activation barrier. The negative charge is dispersed in the adduct, leading to a weaker interaction in a polar solvent. Then, increasing the medium polarity, the energy difference between the adduct and the reactants decreases. We also observed a limit for solvent stabilization in the low dielectric constant range. For example, the results obtained with tetrahydrofuran are closer to those obtained with water than to those obtained with toluene. Considering both the thermodynamics of the reaction and the differential solvent effects, we were able to indicate anions derived from alkyl sulfides as the most convenient for CO2 sequestration among the set here considered.

We report thermodynamic, geometric, and electronic parameters for the interaction between neutral ligands and the [Hg(H2O)]2+ dication, using the B3LYP/6–311 + G(d,p) approach. Gibbs free energies for the interaction were employed to rank the affinity order of the several neutral ligands. To identify the parameters that characterize the affinity between the two fragments, the metal-ligand interaction was analyzed according to the EDA, NBO, and QTAIM decomposition schemes. The phosphine oxide showed the highest affinity for the Hg(H2O)2+ dication, mainly due to the P=O bond polarization. Ligands containing the sulfur atom, characterized by a high covalent component for the metal-ligand interaction, are the following in the interaction order. According to the Gibbs free energy for substitution of one water molecule in the [Hg(H2O)2]2+ complex, the sequence for the affinity order is: phosphine oxide > thioketone > thioesther > lactam > amide > amine > carboxylic acid > thiophene > ketone > esther > thiol > thiocyanate > ammonia > disulfide > aldehyde > ether > haloydrin > alcohol > enol > azide.

Wax deposition is one of the major flow problems for petroleum transportation and production. In this context, the development of more efficient methods to remediate paraffin precipitation has received great attention within the oil industries. In the present study, eight new long-chain esters were prepared in less than four synthetic steps and in high yields (84–97%). Seven of them contain naphthoquinone nuclei, and one presents a cyclohexyl group. The new molecules were tested as non-polymer wax precipitation inhibitors and pour point depressants. Calorimetric experiments were employed to identify the effect of four pre-determined chemical groups within the molecules and to set out the best components for maximized inhibition: (i) the length of alkyl chain in the ester group, (ii) the length of the alkyl chain separating the polar nuclei and the ester group, (iii) the heteroatom bonded to the polar nuclei, and (iv) the importance of the naphthoquinone nuclei. After determination of the pour point and wax appearance temperature (WAT) of Brazilian oils by differential scanning calorimetry (DSC), the highest efficiency was observed for naphthoquinone esters derived from stearic and palmitic acids when containing two methylene groups as a separator and nitrogen as the heteroatom. These new additives present better results than the commercially available polymer-based inhibitors in all tested samples, even when applied at smaller concentrations, compared to many other polymer-based inhibitors reported in the literature. The importance of the naphthoquinone moiety as the polar portion of the inhibitor was confirmed when it was replaced by a cyclohexyl group. Molecular modeling and X-ray diffraction studies were also carried out to rationalize the relationship between structure and activity and the action mechanism of these new chemical additives.

The density functional theory is employed to determine the efficiency of 11 exchange-correlation (XC) functionals to compute the 1 H and 13 C NMR chemical shifts of p -tert-butylcalix[4]arene (ptcx4, R 1 = C(CH 3 ) 3 ) and congeners using the 6-31G(d,p) basis set. The statistical analysis shows that B3LYP, B3PW91 and PBE1PBE are the best XC functionals for the calculation of 1 H chemical shifts. Moreover, the best results for the 13 C chemical shifts are obtained using the LC-WPBE, M06-2X and w B97X-D functionals. The performance of these XC functionals is tested for three other calix[4]arenes: p -sulfonic acid calix[4]arene ( sfxcx4 - R 1 = SO 3 H), p -nitro-calix[4]arene ( ncx4 , R 1 = NO 2 ) and calix[4]arene ( cx4 - R 1 = H). For 1 H chemical shifts B3LYP, B3PW91 and PBE1PBE yield similar results, although B3PW91 shows more consistency in the calculated error for the different structures. For 13 C NMR chemical shifts, the XC functional that stood out as best is LC-WPBE. Indeed, the three functionals selected for each of 1 H and 13 C show good accuracy and can be used in future studies involving the prediction of 1 H and 13 C chemical shifts for this type of compounds.

We synthesized ten enamine naphthoquinones with yields ranging from 43 to 76%. These compounds were screened for their in vitro antiproliferative activities by MTT assay against four types of human cancer cell lines: HCT116, PC3, HL60 and SNB19. The naphthoquinones bearing the picolylamine (7) and quinoline (12) moieties were the most actives (IC50 < 24 μM for all the cell lines), which were comparable or better to the values obtained for the control drugs. In silico evaluations allowed us to develop a qualitative Structure-Activity Relationship which suggest that electrostatic features, particularly the C2-C3 internuclear repulsion and the molecular dipole moment, relate to the biological response. Furthermore, Molecular Docking simulations indicate that the synthetic compounds have the potential to act as anticancer molecules by inhibiting topoisomerase-II and thymidylate synthase.

The authors acknowledge FAPERJ for providing research grants and financial support. MB thanks the School of Chemistry and EaStCHEM for support and for access to a computer cluster maintained by Dr H. Früchtl. JWMC acknowledges CNPq for a research grant. The experimental work was supported via our membership of the UK Catalysis Hub consortium funded by EPSRC (grants EP/K014706/2, EP/K014668/1, EP/K014854/1 and EP/K014714/1). SPN gratefully acknowledges the European Commission for support in the form of an ERC Advanced Researcher grant (227817-FUNCAT). A new mechanism is proposed for the Ni-catalysed carboxylation of organoboronates with CO2. DFT investigations at the PBE0-D3 level have shown that direct CO2 addition to the catalysts [Ni(NHC)(Allyl)Cl] (1NHC, NHC = IMe, IPr, SIPr and IPr*) is kinetically disfavored and formation of the Aresta-type intermediate is unlikely to occur. According to the mechanism proposed here, the carboxylation process starts with addition of the borate species to 1NHC, followed by transmetalation, CO2 cycloaddition and carboxylation. The rate-determining step was identified as being the transmetalation process, with computed relative free energy barriers of 34.8, 36.8 and 33.5 kcal mol-1 for 1IPr, 1SIPr and 1IPr*, respectively Postprint

We quantum chemically explore and analyze 1,3-dipolar cycloadditions of hydrazoic acid and methyl azide with a number of substituted alkenes R-HC=CH2 (R = CH3, OH, OCH3, NH2, CN and NO2) using dispersion-corrected DFT at wB97X-D/6-311++G(d,p). Our purpose is to uncover the physical factors behind the computed trends in reactivity, regioselectivity (1,4 vs. 1,5 addition) and preferred stereochemistry (endo vs. exo). To this end, we use the activation strain model (ASM) and quantitative molecular orbital (MO) theory. One of our main findings is that introducing electron-donating groups in the dipolarophile, R = CH3, OH, OCH3 or NH2, favors the 1,5-cycloaddition. On the other hand, the presence of electron-withdrawing groups, R = CN or NO2, leads to 1,4-addition. Besides, we find a general preference for endo addition, a result that consolidates the endo rule. Trends in the regiochemistry are dictated by the inverse and regular HOMO-LUMO gap, respectively, between dipole and dipolarophile.

Density functional theory (B3LYP) was employed to analyze the metal–support interaction in a Pd4 cluster supported on a γ-alumina model (Al14O24H6) and its effect on the adsorption of a single NO molecule. Our results show that the Pd4–Al14O24H6 interaction leads to a reduction in the cohesion energy among palladium atoms, promoting greater dispersion on the γ-alumina surface. NO preferentially adsorbs in a tilted orientation on the palladium atom anchored on two oxygen atoms, with an adsorption energy of −25.4 kcal mol–1, which is in good agreement with the experimental result of −27.2 ± 1.4 kcal mol–1. The palladium–alumina interaction causes a significant reduction in the NO adsorption energy, suggesting the possible existence of a strong metal–support interaction (SMSI). We observe that the larger the decrease in the adsorption energy, the higher the electronic component of the metal–support interaction. NBO (natural bond orbital) calculations show that such an effect also leads to attenuation of the ...

We reported experimental and theoretical investigation of conformers of 1,2,3-triazole derivatives, substances of exclusively synthetic origin, subject of extensive studies, because of several biological properties, such as antiviral, antimicrobial and antileishmaniasis. We reported molecular/supramolecular X-ray structures of antiophidian compounds I and II. For I and II there are two crystallographic different molecules in the unit cell (A and B). To explore the causes of the similarities in the compound’s crystal structures, intermolecular interactions were explored using the Hirshfeld surface as the fingerprint plots. In addition, density functional theory (DFT) calculations were carried out at the ωB97x-D/6-31G(d,p)-PCM-CHCl3 level aiming to contribute to the interpretation of the experimental data and complement the experimental findings. Two structures named 2A and 5B were found in good agreement with the respective X-ray solid state ones (A and B). Theoretical 1H nuclear magnetic resonance (NMR) spectra calculated for 5B rotated structure (torsion angles deviation around 40° to 90°) was in fine agreement with experimental results (in CDCl3) indicating that the solution molecular structure is considerably different from optimized equilibrium geometries and solid-state structure. Therefore, care is needed when using X-ray structures or DFT geometries to model interaction of drugs with biological targets since significant conformational changes may take place in solution.

The Z-E isomerization of γ-alkylidenebutenolide analogues to natural nostoclides and other natural butenolides was investigated using 1H nuclear magnetic resonance (NMR) and high performance liquid chromatography (HPLC) data as well as density functional theory (DFT) calculations at the wB97x-D/6-31G(d,p) level, including solvent effects with the polarizable continuum solvation approach. The experimental data supported the Z to E isomerization of γ-alkylidenebutenolides under acid catalysis. Newly prepared samples have predominantly Z configuration, which partially isomerizes to the E isomer under acidic conditions. Density functional theory studies corroborate the experimental findings. While neutral γ-alkylidenebutenolides are more stable in the Z form, protonation of the γ-lactone carbonyl group results in preferential stabilization of the E isomer.

Density functional theory calculations (ωB97X-D/6-311++G(d,p)) are employed to investigate an alternative pathway for Prins-like cyclization. Although strong acids usually catalyze this reaction, 4-amino-1,3-dioxanes are rapidly obtained in high yields without catalyst when benzenamines and acetaldehyde react at low temperatures, in aqueous medium. Considering these conditions, we applied a supermolecule model with explicit water molecules to compute the mechanism for 4-amino-1,3-dioxanes formation from the reactants. The structure of the primary solvation shell was determined by Metropolis Monte Carlo method. In the Prins-cyclization step, we found an unpredicted pathway with non-ionic transition structures or intermediates. Explicit water molecules establish a net of hydrogen bonds allowing prototropism, maintaining the electrical neutrality in the system while two protons transfer occurs. To provide data to further experimental confirmation of this hypothesis, we estimated the kinetic isotope effect for the reaction. We also investigated the use of aliphatic amines, which indicates that the reaction may be of a broader application than first observed experimentally.

The Sn-Cl chemical bond of four organotin halides (Me3SnCl, Et3SnCl, Bu3SnCl, and Ph3SnCl) was studied by using relativistic density functional theory in combination with a quantitative energy decomposition analysis to explain the formation of charged species. The σ orbital is the dominant contributor to the stabilization of the Sn-Cl bond, and the π-orbital interactions also have a significant contribution to the stabilization of Ph3Sn+ cation when the aromatic groups are bonded to the tin atom. The aromaticity of the phenyl groups delocalizes the positive charge, donating electrons to tin atom by conjugation. Although Me3SnCl and Ph3SnCl are constituted by groups which the size of the substituents is different, the interaction energies obtained with the energy decomposition analysis present similar values, which also occur with the thermodynamic parameters. Graphical abstract Organotin compounds have widely studied as a potential antitumoral agent. The mechanism in triorganotin compounds includes the formation of cation species, R3Sn+. This article studies the influence of the R groups on the rupture of Sn-Cl bond using the fragment analysis and quantitative energy decomposition analysis.

Carbon dioxide (CO2) and hydrogen (H2) adsorptions were investigated on 3D nitrogen-doped porous graphene (GO-PAA) produced by chemical activation of graphene oxide impregnated with polyallylamine (PAA). GO-PAA characterizations by Raman and X-ray photoelectron spectroscopies, thermogravimetric analysis, N2 adsorption-desorption isotherms, scanning electron microscopy and energy-dispersive X-ray spectroscopy revealed that GO-PAA shows excellent thermal stability, decomposing at temperatures higher than 450 °C, specific surface area of 1155 m2 g−1, with pyrrolic, pyridinic and graphitic nitrogen atoms homogeneously dispersed throughout its 3D porous structure. The mesoporous nature of GO-PAA and the nitrogen doping level of 7.5 wt% resulted in remarkable H2 (1.3 wt%) and CO2 (20 mmol g−1) adsorption capacities at room temperature (RT, 25 °C) under high-pressure regime (40 bar). This H2 adsorption capacity at RT is among the highest values reported in the open literature. The role of the nitrogen atoms on the gas adsorption properties was investigated by combining experimental data, such as isosteric heat and Diffuse Reflectance Infrared Fourier Transform spectroscopy, with theoretical calculations using Density-Functional Theory. Inclusion of nitrogen atoms in the graphene structure reduces the energies of the Frontier Molecular Orbitals, facilitating polarization and increasing the interaction energy.

Although CO2 capture by alkanolamine aqueous solutions is a well-established technology, it demands high energy penalties and water consumption. Therefore, the development of new methods for CO2 removal is still a challenge. Herein, we employed the Density Functional Theory (DFT) to explore the potential of different mixtures composed of glycerol and nitrogen-containing bases to capture CO2. By combining glycerol, CO2 and the bases, it was possible to show that aliphatic amines are able to form intermolecular hydrogen bonds with the primary hydroxyl groups of glycerol, increasing their nucleophilicity and assisting the reaction with CO2 to form glycerol carbonate as the most stable product. To confirm that glycerol carbonate would be experimentally obtained from the given mixture, we selected triethylamine (TEA) to assist glycerol (Gly) in its reaction with CO2. The resulting product was characterized by Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR), 1D and 2D Nuclear Magnetic Resonance spectroscopy (1H and 13C NMR) and Thermogravimetric Analysis (TGA). The ATR-FTIR results showed that TEA is protonated after bubbling CO2 in the glycerol/TEA mixture, suggesting that the reaction with CO2 occurs after deprotonation of glycerol, forming organic carbonates, as also indicated in the NMR spectra. The combined theoretical and experimental results indicate that TEA is able to activate glycerol in its reaction with CO2 to form organic carbonates, being an alternative procedure for CO2 capture.

Molecules carrying the azido functionality are widely used as intermediates in medicinal chemistry. Pyrrolobenzodiazepines are molecules with a broad range of interesting pharmacological properties. Due to the wide importance of azido-PBD as a key intermediate in many synthetic pathways, in this work we have investigated the effect of a variety of experimental parameters on the mechanism of nucleophilic substitution reaction for introducing an azide group into the PBD scaffold. This study was carried out by combined experimental and DFT approaches, showing that SN2 and double SN2 pathways are possible and highly dependent on the reaction temperature.

Raman and infrared spectroscopy were applied for the vibrational characterization of lapachol and its pyran derivatives, α-lapachone and β-lapachone. Experimental spectra of solid state samples were acquired between 4000 and 100 cm−1 in Raman experiments, and between 4000 and 600 cm−1 (mid-infrared) and 600–100 cm−1 (far-infrared) with FTIR spectroscopy, respectively. Full structure optimization and theoretical vibrational wavenumbers were calculated at the B3LYP/6-31 + + G(d,p) level. Detailed assignments of vibrational modes in an experimental and theoretical spectra were based on potential energy distribution analyses, using Veda 4.1 software. Clear differentiation between the three compounds was verified in the region between 1725 and 1525 cm−1, in which the ν(CO) and ν(CC) modes of the quinone moiety were assigned.

A mixture of the E and Z isomers of ethyl 2-cyano-3-((4-fluorophenyl)amino) acrylate was synthesized and characterized by elemental analysis, attenuated total reflectance-Fourier transform infrared spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopy. The structure of the Z isomer was determined by single crystal X-ray diffraction, which revealed a three-dimensional supramolecular network governed by C H⋯N, C H⋯O, and C H⋯F hydrogen bonds and π⋯π stacking interactions. The combination of these interactions plays an important role in stabilizing the self-assembly process and the molecular conformation. Hirshfeld surface analysis indicated the roles of the noncovalent interactions in the crystal packing, which were quantified by fingerprint plots and DFT calculations.

1H and 13C NMR chemical shifts were measured for three phosphoramidates and computed using the B3LYP, WP04, TPSSh, M06-2X and wB97X-D density functionals. The experimental and computed chemical shifts for hydrogen and carbon were compared using linear correlation (R2), mean absolute error (MAE), root mean squared deviation (RMSD) and DP4 analysis. Applying a linear correction to the computed data improves the absolute accuracy and reduces random errors. For 13C NMR shift data, results from the GIAO/wB97X-D/cc-pVTZ/SCRF combination show the lowest value of RMSD (2.073). For 1H NMR shift data, CSGT/TPSSh/cc-pVTZ/SCRF shows RMSD of 0.070. The method that best applies to this class of compounds is CSGT/wB97X-D/cc-pVTZ/SCRF. DP4 analysis was used to correlate the chemical shifts (1H and 13C NMR) of the compounds and indicated that the method that best applies to this class of compounds is CSGT/wB97X-D/cc-pVTZ/SCRF, with DP4 analysis of 51.9%. In general, the best results were obtained when using implicit solvation model during calculations. The best method was applied on an external test set of 6 additional molecules and provided satisfactory results.

Prostate cancer is an important cause of death in the male population and for which there is no satisfactory chemotherapy. Herein a new series of chalcone hybrids containing 2H-1,2,3-triazole core as the ring B has been synthesized and evaluated in vitro against PC-3 prostate cancer cell line. Compounds 4a, 4c and 4e significantly reduced cell viability and showed IC50 of 28.55, 15.64 and 25.56 µM, respectively. The structure-activity relationship supported by computational chemistry points that the polarity of the molecular surface area should have some relevance to the efficiency of the compounds, in particular the ratio of the partial positive charge sites and the total molecular surface area exposed to the cell environment.

Glycerine is a by-product from biodiesel production. After transesterification using methanol, the oil from Jatropha seeds produces high amounts of stearic and palmitic methyl esters and about 10%wt. in glycerol. This chapter deals with the different aspects of the valorization of glycerine for the production of propylene glycol (1,2-PD). After introducing the subject, we evaluate the glycerol and 1,2-PD markets, particularly for pharmaceutical use. We then describe the processes of aqueous-phase hydrogenolysis (APH), aqueous-phase reforming (APR), and catalytic hydrogen transfer (CTH) applied to glycerol and describe some thermodynamics aspects and metal catalysts applied to these processes. Finally, we discuss some detailed kinetic models and application of molecular modeling to this reaction.

Hydrogen sulfide, H2S, stand as one of the major issues in petroleum industry. Aqueous solutions of triazines are the most utilized non-regenerative H2S scavenger. Although they present a theoretical capture capacity of 3 mol of H2S per mole of triazine, it effectively scavenges only 2 mol. Herein, we employed Density Functional Theory at CAM-B3LYP/6–311++G(2d,2p) level of calculation to rationalize the full mechanism for capture of H2S by hexahydro-1,3,5-triazines, in particular the reason why the reaction stops at the second equivalent of H2S. For the capture of the first equivalent of H2S, we found an unprecedented SN1 pathway to be less energetic than SN2, the most commonly accepted in literature. For capture of a second H2S molecule, however, both mechanisms are energetically similar. High barriers were found for the capture of the third molecule of H2S, related to the lower electrophilicity of the carbon atom bonded to nitrogen and sulfur atoms.

Combined experimental and mixed implicit/explicit solvation approaches were employed to gain insights into the origin of switchable regioselectivity of acid‐catalyzed lapachol cyclization and α‐/β‐lapachone isomerization. It was found that solvating species under distinct experimental conditions stabilized α‐ and β‐lapachone differently, thus altering the identity of the thermodynamic product. The energy profile for lapachol cyclization revealed that this process can occur with low free‐energy barriers (lower than 8.0 kcal mol−1). For α/β isomerization in a dilute medium, the computed enthalpic barriers are 15.1 kcal mol−1 (α→β) and 14.2 kcal mol−1 (β→α). These barriers are lowered in concentrated medium to 11.5 and 12.6 kcal mol−1, respectively. Experimental determination of isomers ratio was quantified by HPLC and NMR measurements. These findings provide insights into the chemical behavior of lapachol and lapachone derivatives in more complex environments.

Hematite (α-Fe2O3) has been used as an ethanol gas sensor and as a catalyst for nanomaterial synthesis, motivating the investigation of ethanol dehydration over a hematite surface using computational chemistry methods. Using a molecular approach and a simple model for α-Fe2O3 to mimic the catalyst effect on the thermodynamics and kinetics of the reaction and quantum chemical Density Functional Theory (DFT) calculations, we showed that the energy barrier for the formation of ethylene plus water is around 70% lower than the corresponding gas phase value and that the products are thermodynamically stable with respect to the ethanol reactant in the presence of a non-planar model catalyst (Fe10O15). This stimulating result supports a mechanism proposed for ethylene formation at mild temperatures using hematite as a catalyst. We also showed that the effect of a catalyst on a chemical process can be very satisfactorily simulated as a local effect through first principles quantum chemical calculations, being of practical use, and so, large cluster calculations with many atomic layers or the use of large periodic super cells are not strictly required to reach reasonable estimates of temperature dependent rate constants and products stabilization. Our results strongly support a proposal that the main intermolecular interactions between the species present in a chemical process and the catalyst, leading to stabilization of transition state structure and consequent reduction of energy barrier can be fairly described by the DFT level of theory using small molecular models based on sound chemical ground.