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A tetrahydro-4 H-(pyrrolo[3,4- d]isoxazol-3-yl)methanamine scaffold was designed as a diamino derivative to stabilize parallel turn conformations. Its synthesis took advantage of a [1,3]-dipolar cycloaddition reaction between the nitrile oxide derived from the inexpensive enantiopure l -phenylalanine and N-benzyl-3-pyrroline. Two diastereoisomers were formed, whose distribution depends on the selected base. 3a R,6a S-Isomer is favored in organic bases, which formation is driven by π-interactions. However, the above interactions were significantly prevented using an inorganic base due to the chaotropic effect of the cation, decreasing the amount of the above isomer. Finally, we demonstrated that this isomer is able to stabilize parallel turn conformations when inserted in short peptide sequences.
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A new α,α-disubstituted constrained glutamine analogue has been designed to decorate gold nanoparticles and to induce a 310-helix when inserted in peptides. Using an efficient "one-pot" asymmetric Schmidt reaction between 4-disubstituted-cyclohexanone and hydroxyalkylazides, 1H-azepine-2-oxo-5-amino-5-carboxylic acid was prepared. The main (R) isomer was inserted at the N-terminus in a very short peptide sequence (i.e., PhCO-(R)-Oxo-Azn-L-Ala-Aib-L-AlaNHMe) and a stable 310-helix conformation was obtained, as verified by both NMR experiments and molecular dynamics (MD) simulations. Finally, the presence of the hydroxyl chain at the nitrogen atom of the ring allowed for the preparation of covered chiral gold nanoparticles.
Assuntos
Azepinas/química , Ácidos Carboxílicos/síntese química , Ouro/química , Nanopartículas/química , Peptídeos/química , Sequência de Aminoácidos , Azepinas/síntese química , Ácidos Carboxílicos/química , Espectroscopia de Ressonância Magnética , Modelos Moleculares , EstereoisomerismoRESUMO
A new semirigid dipeptide mimetic was prepared on multigram scale, in good yield, and in a stereocontrolled way, starting from commercially available and unexpensive reagents, i.e., N-benzylpiperidone, tosyl azide, and proline methyl ester. The optimized multicomponent process consisted of a cascade click cycloaddition and a ring rearrangement reaction, followed by a reductive step. Theoretical calculations were performed to elucidate the reaction mechanism and support the stereochemical outcome of the reduction. Finally, the new scaffold was used for the preparation of model peptidomimetics, whose ß turn conformation was confirmed by dynamic NMR experiments.
Assuntos
Boroidretos/química , Dipeptídeos/síntese química , Prolina/química , Catálise , Química Click , Reação de Cicloadição , Espectroscopia de Ressonância Magnética , Conformação Molecular , Estereoisomerismo , Compostos de Tosil/químicaRESUMO
This work aims at studying why azodicarbonamide (ADCA), a formally apolar compound with good hydrogen bond (HB) acceptors, is soluble only in polar aprotic solvents like dimethyl sulfoxide (DMSO) but not in water. Solubility measurements, as well as quantum mechanical and classical molecular dynamics simulations, were employed to tackle the problem. We found that in the liquid phase a polar conformer of ADCA (µ = 8.7 D), unreported to date, is favoured under the enthalpic drive provided by a highly polar solvent. At the same time, the very high hydrogen bond propensity of water with itself prevents this solvent from providing an effective hydrogen bond-mediated solvation. Solvents bearing good HB acceptors, while lacking strong HB donors, contribute to further stabilizing solute-solvent adducts through weak and fluxional HBs that involve the amide groups of ADCA. Implications for the solubility of ADCA down to µM concentrations were evaluated, also with the aid of classical simulations of solution nanodroplets.
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Herein, the integration of SnO2 nanoparticles with two Zn(II) porphyrinsâZn(II) 5,10,15,20-tetraphenylporphyrin (ZnTPP) and its perfluorinated counterpart, Zn(II) 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (ZnTPPF20)âwas investigated for the sensing of gaseous acetone at 120 °C, adopting three Zn-porphyrin/SnO2 weight ratios (1:4, 1:32, and 1:64). For the first time, we were able to provide evidence of the correlation between the materials' conductivity and these nanocomposites' sensing performances, obtaining optimal results with a 1:32 ratio for ZnTPPF20/SnO2 and showcasing a remarkable detection limit of 200 ppb together with a boosted sensing signal with respect to bare SnO2. To delve deeper, the combination of experimental data with density functional theory calculations unveiled an electron-donating behavior of both porphyrins when interacting with tin dioxide semiconductor, especially for the nonfluorinated one. The study suggested that the interplay between electrons injected, from the porphyrins' highest occupied molecular orbital to SnO2 conduction band, and the latter's available electronic states has a dramatic impact to boost the chemiresistive sensing. Indeed, we highlighted that the key lies in preventing the full saturation of SnO2 electronic states concomitantly increasing the materials' conductivity: in this respect, the best compromise turned out to be the perfluorinated porphyrin. A further corroboration of our findings was obtained by illuminating the sensors during measurements with light-emitting diode (LED) light. Actually, we demonstrated that it does not have any impact on improving the sensing behavior, most probably due to the electronic oversaturation and scattering caused by LED excitation in porphyrins. Lastly, the most effective hybrids (1:32 ratio) were physicochemically characterized, confirming the physisorption of the macrocycles onto the SnO2 surface. In conclusion, herein, we underscore the feasibility of customizing the porphyrin chemistry and porphyrin-to-SnO2 ratio to enhance the gaseous sensing of bare metal oxides, providing valuable insights for the engineering of highly performing light-free chemiresistors.
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The accurate, experimental charge density distribution, ρ(r), of the potent antimalarial drug dihydroartemisinin (DHA) has been derived for the first time from single-crystal X-ray diffraction data at T=100(2)â K. Gas-phase and solid-state DFT simulations have also been performed to provide a firm basis of comparison with experimental results. The quantum theory of atoms in molecules (QTAIM) has been employed to analyse the ρ(r) scalar field, with the aim of classifying and quantifying the key real-space elements responsible for the known pharmacophoric features of DHA. From the conformational perspective, the bicyclo[3.2.2]nonane system fixes the three-dimensional arrangement of the 1,2,4-trioxane bearing the active O-O redox centre. This is the most nucleophilic function in DHA and acts as an important CHâ â â O acceptor. On the contrary, the rest of the molecular backbone is almost neutral, in accordance with the lipophilic character of the compound. Another remarkable feature is the C-O bond length alternation along the O-C-O-C polyether chain, due to correlations between pairs of adjacent C-O bonds. These bonding features have been related with possible reactivity routes of the α- and ß-DHA epimers, namely 1)â the base-catalysed hemiacetal breakdown and 2)â the peroxide reduction. As a general conclusion, the base-driven proton transfer has significant non-local effects on the whole polyether chain, whereas DHA reduction is thermodynamically favourable and invariably leads to a significant weakening (or even breaking) of the O-O bond. The influence of the hemiacetal stereochemistry on the electronic properties of the system has also been considered. Such findings are discussed in the context of the known chemical reactivity of this class of important antimalarial drugs.
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Antimaláricos/química , Artemisininas/química , Antimaláricos/farmacologia , Artemisininas/farmacologia , Modelos Teóricos , Conformação Molecular , Estrutura Molecular , Difração de Raios XRESUMO
The title 1,4-naphthoquinone, 2-dichloromethyl-3-methyl-1,4-dihydronaphthalene-1,4-dione, C12H8Cl2O2, is a chlorinated derivative of vitamin K3, which is a synthetic compound also known as menadione. Molecules of (I) are planar and lie on a crystallographic mirror plane (Z' = 0.5) in the space group Pnma. They are connected to each other by C-H···O hydrogen bonds, forming two-dimensional layers parallel to the ac plane. In addition, Cl···Cl and π-π interactions link adjacent molecules in different layers, thus forming zigzag ribbons along the b axis, such that a three-dimensional architecture is generated.
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The accurate gas-phase equilibrium structures on the ground-state potential energy surface of the complete series of fluorinated and chlorinated cyclobutene derivatives with C(2v) symmetry have been evaluated at DFT PBE0/6-311++G(d,p) theory level. The optimized geometries have been compared with all the available experimental data reported in the literature, as obtained by microwave spectroscopy (MW) and gas-phase electron diffraction (GED) techniques. For hexafluorocyclobutene and 1,2-dichloro-3,3',4,4'-tetrafluorocyclobut-1-ene, the results of accurate low-temperature single-crystal X-ray diffraction experiments have also been considered. Structural changes within the cyclobutene ring, as induced by fluorination and chlorination at allylic and vinylic positions, have been correlated with changes in the corresponding theoretical charge densities. To this aim, several local and nonlocal topological descriptors provided by the quantum theory of atoms in molecules, QTAIM, have been employed, with particular emphasis on the delocalization indices and integrated source function decomposition schemes. Key factors for the resulting molecular structures are the chemical nature and the steric hindrance of the substituents, as well as quantum-mechanical effects, such as delocalization and partial conjugation. When fluorine atoms replace hydrogens at allylic or vinylic positions, the corresponding Csp(3)-Csp(3) or Csp(2)âCsp(2) bonds between the substituted carbons undergo a significant strengthening, while chlorination has just the opposite effect. In the latter case the steric hindrance between bulky chlorine atoms occupying vicinal positions is crucial in determining the single Csp(3)-Csp(3) bond length. These findings are discussed in the context of the reactivity of chemically related chlorofluorocarbon compounds.
Assuntos
Ciclobutanos/química , Hidrocarbonetos Halogenados/síntese química , Elétrons , Hidrocarbonetos Halogenados/química , Estrutura Molecular , Teoria QuânticaRESUMO
Polymorphism in the highly flexible organic Schiff-base macrocycle ligand 3,6,9,17,20,23-hexa-azapentacyclo(23.3.1.1(11,15).0(2,6).0(16,20))triaconta-1(29),9,11,13,15(30),23,25,27-octaene (DIEN, C(24)H(30)N(6)) has been studied by single-crystal X-ray diffraction and both solid-state and gas-phase density functional theory (DFT) calculations. In the literature, only solvated structures of the title compound are known. Two new polymorphs and a new solvated form of DIEN, all obtained from the same solvent with different crystallization conditions, are presented for the first time. They all have P\bar 1 symmetry, with the macrocycle positioned on inversion centres. The two unsolvated polymorphic forms differ in the number of molecules in the asymmetric unit Z', density and cohesive energy. Theoretical results confirm that the most stable form is (II°), with Z' = 1.5. Two distinct molecular conformations have been found, named `endo' or `exo' according to the orientation of the imine N atoms, which can be directed towards the interior or the exterior of the macrocycle. The endo arrangement is ubiquitous in the solid state and is shared by two independent molecules which constitute an invariant supramolecular synthon in all the known crystal forms of DIEN. It is also the most stable arrangement in the gas phase. The exo form, on the other hand, appears only in phase (II°), which contains both the conformers. Similarities and differences among the occurring packing motifs, as well as solvent effects, are discussed with the aid of Hirshfeld surface fingerprint plots and correlated to the results of the energy analysis. A possible interconversion path in the gas phase between the endo and the exo conformers has been found by DFT calculations; it consists of a two-step mechanism with activation energies of the order of 30-40 kJ mol(-1). These findings have been related to the empirical evidence that the most stable phase (II°) is also the last appearing one, in accordance with Ostwald's rule.
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A new monoclinic form of the title compound, C(14)H(17)N(3)O(3)S, has been found upon slow crystallization from water. Another monoclinic form of the compound was obtained previously from a mixture of dichloro-methane and diethyl ether [Clerici et al. (2002 â¶). Tetra-hedron, 58, 5173-5178]. Both phases crystallize in space group P2(1)/n with one mol-ecule in the asymmetric unit. The formally single exocyclic C-N bond that connects the -NEt(2) unit with the thia-zete ring is considerably shorter than the adjacent, formally double, endocyclic C=N bond. This is likely to be due to the extended conjugated system between the electron-donor diethyl-ammine fragment and the electron-withdrawing sulfonyl group. In the newly discovered polymorph, the meth-oxy group is rotated by almost 180° around the phen-yl-OCH(3) bond, resulting in a different mol-ecular conformation.
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The exploitation of self-assembled systems to improve the solubility of drugs is getting more and more attention. Among the different types of self-assembled biomaterials, peptides and in particular peptides containing non-coded amino acids (NCAPs) are promising because their use opens the door to more stable materials inducing increased stability to proteolysis. New classes of NCAP, Ac-Ala-X-Ala-Aib-AlaCONH2 (X = alpha-aminoisobutyric acid (Aib) or X = cyclopentane amino acid (Ac5c)) have been prepared and the correlation between the different secondary peptide structure and solvent (i.e. CD3CN, CD3OH, H2O/D2O) verified by NMR. Furthermore, the formation of a nanocolloidal system in water was deeply studied by DLS and the morphology of the obtained spherical aggregates with nanometric dimensions was assessed by TEM. Aib containing pentapeptide was selected for greater ease of synthesis. Its ability to encapsulate curcumin, as a model insoluble drug molecule, was investigated using fluorescence emission and confocal microscopy analyses. Two different approaches were used to study the interaction between curcumin and peptide aggregates. In the first approach peptide aggregates were formed in the presence of curcumin, while in the second approach curcumin was added to the already formed peptide aggregates. We succeeded in our challenge by using the second approach and 53.8% of added curcumin had been encapsulated.
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We observed a 73% enhancement of the power conversion efficiency (PCE) of a photovoltaic cell based on a single wall carbon nanotube/Si hybrid junction after exposing the device to a limited amount (10 ppm) of NO2 diluted in dry air. On the basis of a computational modeling of the junction, this enhancement is discussed in terms of both carbon nanotube (CNT) p-doping, induced by the interaction with the oxidizing molecules, and work function changes across the junction. Unlike studies so far reported, where the PCE enhancement was correlated only qualitatively to CNT doping, our study (i) provides a novel and reversible path to tune and considerably enhance the cell efficiency by a few ppm gas exposure, and (ii) shows computational results that quantitatively relate the observed effects to the electrostatics of the cell through a systematic calculation of the work function. These effects have been cross-checked by exposing the cell to reducing molecules (i.e·NH3) that resulted to be detrimental to the cell efficiency, consistently with the theoretical ab-initio calculations.
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The total experimental electron density distributions rho(r) of zwitterionic L- and DL-alanine crystals, as derived from extensive sets of X-ray diffracted intensities collected at 23 and 19 K, are compared to gain an insight into the different physical properties of the two related chiral compounds in the solid state and to explore the extent of the rho(r) transferability. Relevant parameters that characterize the two crystal forms are obtained, showing differences and similarities in terms of (i) geometric descriptors, (ii) topological indexes, (iii) molecular electrostatic potential Phi(r) distributions, (iv) atomic volumes and charges, (v) molecular electric moments, and (vi) electrostatic interaction energies. To assess the relative stability of the racemate with respect to the pure enantiomer, the crystal lattice energies, as obtained through DFT fully periodic calculations, are also discussed and compared with the experimental sublimation enthalpies after correction for the proton-transfer energies. In-crystal group charges, evaluated with the quantum theory of atoms in molecules, are found to be transferable between the racemic and the pure enantiomer, at variance with group volumes. Similarly, molecular first and third moments are not strictly transferable and indicate that for the zwitterionic alanine molecule the molecular charge distribution in the DL-crystal is more polarized in the c direction by about 10%. By contrast, quantitative agreement is observed for second and fourth moments. Significant differences arise from (1) the crystal packing of the dipole vectors, which are aligned in an antiparallel fashion in the L-crystal, to be compared with a parallel alignment in the racemate, due the polar space group Pna21 of the latter, (2) the strongly attractive electrostatic energy of a homochiral pair in the L-crystal, which is opposed to the corresponding heterochiral pair in the DL-crystal form. The difference between these Ees values amounts to 135-150 kJ mol(-1). Despite this, the two crystal forms are predicted as equally thermodynamically favored by the theoretical P-B3LYP estimates of the crystal lattice energies. Finally, the necessity of an upgrading of the dispersion and exchange-repulsion terms currently adopted within the experimental charge density approach to intermolecular interactions is recognized and discussed.
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We report the electronic, magnetic and transport properties of a prototypical antiferromagnetic (AFM) spintronic device. We chose Cr as the active layer because it is the only room-temperature AFM elemental metal. We sandwiched Cr between two non-magnetic metals (Pt or Au) with large spin-orbit coupling. We also inserted a buffer layer of insulating MgO to mimic the structure and finite resistivity of a real device. We found that, while spin-orbit has a negligible effect on the current flowing through the device, the MgO layer plays a crucial role. Its effect is to decouple the Cr magnetic moment from Pt (or Au) and to develop an overall spin magnetization. We have also calculated the spin-polarized ballistic conductance of the device within the Büttikerâ»Landauer framework, and we have found that for small applied bias our Pt/Cr/MgO/Pt device presents a spin polarization of the current amounting to ≃25%.
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The structural origin of absorption and fluorescence anisotropy of the single crystal of the π-conjugated heterocyclic system 5,6,10b-tri-aza-acephenan-thrylene, TAAP, is presented in this study. X-ray analysis shows that the crystal framework in the space group P [Formula: see text] is formed by centrosymmetric dimers of face-to-face mutually oriented TAAP molecules joined by π-π non-covalent interactions. The conformation of the TAAP molecule is stabilized by intramolecular C-Hâ¯N(sp2), N(sp2)Hâ¯π(CN), and C-Hâ¯O(sp2) hydrogen bonds. The presence of weak π-π interactions is confirmed by quantum theory of atoms in molecules (QTAIM) and non-covalent interaction (NCI) analysis. The analysis of the optical spectra of TAAP in solution and in the solid state does not allow the specification of the aggregation type. DFT calculations for the dimer in the gas phase indicate that the lowest singlet excitation is forbidden by symmetry, suggesting H-type aggregation, even though the overall absorption spectrum is bathochromically shifted as for the J-type. The experimental determination of the permanent dipole moment of a TAAP molecule in 1,4-dioxane solution indicates the presence of the monomer form. The calculated absorption and emission spectra of the crystal in a simple approximation are consistent with the experimentally determined orientation of the absorption and emission transition dipole moments in TAAP single crystals. The electrostatic interaction between monomers with a permanent dipole moment (ca 4 D each) could result in the unusual spectroscopic JH-aggregate behaviour of the TAAP dimer.
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The possible occurrence of static/dynamic disorder at the Mg site in pyrope (Mg3Al2Si3O12), with or without anharmonic contribution to the thermal vibrations even at low temperatures, has been largely debated but conclusions were contrasting. Here a report is given on the experimental charge density distribution, ρEXP, of synthetic pyrope at T = 30â K, built through a Stewart multipolar expansion up to l = 5 and based on a very precise and accurate set of in-home measured single-crystal X-ray diffraction amplitudes with a maximum resolution of 0.44â Å. Local and integral topological properties of ρEXP are in substantial agreement with those of ρTHEO, the corresponding DFT-grade quantum charge density of an ideal pyrope crystal, and those derived from synchrotron investigations of chemical bonding in olivines. Relevant thermal atomic displacements, probably anharmonic in nature, clearly affect the whole structure down to 30â K. No significant (> 2.5σ) residual Fourier peaks are detectable from the ρEXP distribution around Mg, after least-squares refinement of a multipole model with anharmonic thermal motion at the Mg site. Experimental findings were confirmed by a full analysis of normal vibration modes of the DFT-optimized structure of the perfect pyrope crystal. Mg undergoes wide displacements from its equilibrium position even at very low temperatures, as it is allocated in a â¼â 4.5â Å large dodecahedral cavity and involved in several soft phonon modes. Implications on the interplay among static/dynamic disorder of Mg and lattice vibrational degrees of freedom are discussed.
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The total experimental electron density rho(r), its Laplacian inverted delta(2)rho(r), the molecular dipole moment, the electrostatic potential phi(r), and the intermolecular interaction energies have been obtained from an extensive set of single-crystal X-ray diffracted intensities, collected at T = 70(1) K, for the fungal metabolite austdiol (1). The experimental results have been compared with theoretical densities from DFT calculations on the isolated molecule and with fully periodic calculations. The crystal structure of (1) consists of zigzag ribbons extended along one cell axis and formed by molecules connected by both OH...O and CH...O interactions, while in a perpendicular direction, adjacent molecules are linked by short CH...O intermolecular contacts. An extensive, quantitative study of all the intra- and intermolecular H...O interactions, based not only on geometrical criteria, but also on the topological analysis of rho(r), as well as on the evaluation of the pertinent energetics, allowed us (i) to assess the mutual role of OH...O and CH...O interactions in determining molecular conformation and crystal packing; (ii) to identify those CH...O contacts which are true hydrogen bonds (HBs); (iii) to determine the relative hydrogen bond strengths. An experimental, quantitative evidence is given that CH...O HBs are very similar to the conventional OH...O HBs, albeit generally weaker. The comparison between experimental and theoretical electric dipole moments indicates that a noticeable charge rearrangement occurs upon crystallization and shows the effects of the mutual cooperation of HBs in the crystal. The total intermolecular interaction energies and the electrostatic energy contribution obtained through different theoretical methods are reported and compared with the experimental results. It is found that the new approach proposed by Spackman, based on the use of the promolecular charge density to approximate the penetration contribution to intermolecular electrostatic energies, predicts the correct relative electrostatic interaction energies in most of the cases.
Assuntos
Aldeídos/química , Benzopiranos/química , Fungos/química , Conformação Molecular , Cristalografia por Raios X , Modelos MolecularesRESUMO
High-resolution X-ray diffraction data were collected at T = 19 K from two similar spherical crystals of the fungal metabolite citrinin, C(13)H(14)O(5). The two data sets were of markedly different quality, one data set (MQ, medium quality) comprising a single octant of the reciprocal lattice and including reflections with obviously peculiar intensity profiles while the second (HQ, high quality) comprised a hemisphere of reflections and showed no flawed profiles. Parallel multipolar refinements were carried out for both. While most of the resulting geometric parameters, including bond lengths and angles, were in close agreement (the standard uncertainties were approximately twice as large for the MQ data, reflecting the smaller number of observations), the agreement is noticeably worse for electronic properties such as electron densities and their Laplacians at the bond and ring critical points. These latter features are especially sensitive to the quality of the low-angle (and strong) intensities, which was not high for the MQ data. By contrast, the magnitudes of the molecular dipole moment from the two experiments are the same within 1 standard uncertainty, with an angle of about 13 degrees between the two vectors. It is concluded that only true high-quality data allow a fully significant and quantitative analysis of the details of the experimental electron density rho(exp), while high-resolution medium-quality data, measured at very low temperature and adequately processed, can still be used for a qualitative analysis, or for the derivation of overall electronic properties.
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Citrinina/química , Indolquinonas/química , Temperatura , Difração de Raios XRESUMO
We present relevant results dealing with the transparency/optical nonlinearity trade-off in high-frequency electro-optic applications. The very simple, stable and high optical gap chromophore, the zwitterion 1-methyl-4-(tetrazol-5-ate)pyridinium, represents the best transparency/optical nonlinearity trade-off so far described in the literature. We rationalize this remarkable performance in the framework of the Bond Length Alternation theory by means of a multidisciplinary approach including: single crystal X-ray structure, Electric Field Induced Second-Harmonic Generation, solvatochromism, electrochemistry and thermal analyses.
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Piridinas/química , Tetrazóis/química , Cristalografia por Raios X , Modelos Moleculares , Estrutura Molecular , Raios UltravioletaRESUMO
The conversion of a di-tert-butyl-methylthiiranium ion into thietanium ion, that is reported in the literature as taking place spontaneously at 25 degrees C in a CD(2)Cl(2) solution, has been discovered to occur quantitatively at room temperature (RT) also in the crystalline state. The ring enlargement reaction is accompanied, in the solid phase, by a modest deterioration of the quality of the sample under investigation, and all three specimens here studied by in situ crystallography maintained their single-crystal nature up to 100% conversion. The rearrangement reaction implies the breaking of a C-S bond and the formation of a new bond of the same type, together with the migration of a methyl group. The extent of the corresponding atomic displacements has been measured by comparing the initial and final crystal structures. Several intermediate stages of the process have been investigated and characterized by the site occupancy factor of the episulfonium ion. The RT temporal evolution of this factor and that of the unit-cell volume indicate multi-step kinetics, with processes of simple molecular reorientation or displacement before and after the main, central stage, where the conversion reaction takes place. The overall kinetics is well described by an Avrami-Erofeev equation, with exponent m = 1.75(3) and rate coefficient k = 10.4(3) x 10(-8) s(-1) at 25 degrees C. Ab initio calculations in the gas phase predict a three-step mechanism resulting in a slightly spontaneous reaction with an overall decrease of entropy.