DFT/TDDFT investigation of the stepwise deprotonation in tetracycline: pK<Subscript>a</Subscript> assignment and UV–vis spectroscopy

Tetracyclines are a class of derivatives of polycyclic naphthacene carboxamide, which have attracted wide interest in the pharmaceutical field for their use as antibiotics. These molecules are characterized by a substantial conformational flexibility and by the presence of different binding sites which endow tetracycline with a noticeable capability in binding biological targets. A salient property of tetracyclines is the presence of multiple acidic groups: four equilibrium constants have been measured for the fully protonated tetracycline (TCH₃ ⁺) but so far no clear information concerning the pK_as of the various sites has been reported. We present here a computational investigation on the correlation between the acid–base and the spectroscopic properties of this important class of compounds. Starting from the TCH₃ ⁺ species, the pK_a of all the possible deprotonation sites has been computed by DFT calculations. The computed pK_as nicely compare with the experimental data, within 1 pK_a unit, allowing us to individuate the products of the first deprotonation. This procedure has been iteratively repeated using as starting species the products singled out from the previous deprotonation, thus individuating the stepwise products of each deprotonation step. Then, the optical absorption spectra have been computed for all the species involved in the protonation/deprotonation equilibria, comparing the results with the experimental data. The good agreement between theory and experiment has allowed us to rationalize the correlation between the solution pH and the absorption spectra.     

The effect of the boundary conditions on in-plane and out-of-plane stress field in three dimensional plates weakened by free-clamped V-notches

Dealing with the material microstructure an analytical multiscale model has recently been developed by Sih. Physically, the different orders of the stress singularities are related to the different constraints associated with the defect thought as a microscopic V-notch at the tip of the main crack. Irregularities of the material microstructure tend to curl the crack tip being the clamped-free boundary conditions the more realistic and general representation of what occurs on the microscopic V-notch. As a result, mixed mode conditions are always present along the V-notch bisector line.It is known for a long time that at the antisymmetric (mode II) stress distribution ahead of the crack tip generates a coupled out-of-plane singular mode. Recent theoretical and numerical analyses have demonstrated that this out-of-plane mode due to three-dimensional effects occurs also in the case of large V-notches where the mode II stress field is no longer singular. In addition, when the notch opening angle is non-zero, the three-dimensional singular stress state is strongly influenced by the plate thickness.The aim of this paper is to investigate the effect of free-fixed boundary conditions along the notch edges in three dimensional plates weakened by pointed V-notches and quantify the intensity of the out-of-plane singularity occurring under this constraint configuration. For the sake of simplicity a macronotch is considered rather than a micronotch. A synthesis of the magnitude of the stress state through the plate thickness is carried out by using the mean value of the strain energy density over a given control volume embracing the notch tip. The capability of the strain energy density to capture all the combined effects due to the out-of-plane mode make it a powerful parameter at every scale levels.     

Fluorescence lifetimes and quantum yields of rhodamine derivatives: new insights from theory and experiment

Although lifetimes and quantum yields of widely used fluorophores are often largely characterized, a systematic approach providing a rationale of their photophysical behavior on a quantitative basis is still a challenging goal. Here we combine methods rooted in the time-dependent density functional theory and fluorescence lifetime imaging microscopy to accurately determine and analyze fluorescence signatures (lifetime, quantum yield, and band peaks) of several commonly used rhodamine and pyronin dyes. We show that the radiative lifetime of rhodamines can be correlated to the charge transfer from the phenyl toward the xanthene moiety occurring upon the S(0) ← S(1) de-excitation, and to the xanthene/phenyl relative orientation assumed in the S(1) minimum structure, which in turn is variable upon the amino and the phenyl substituents. These findings encourage the synergy of experiment and theory as unique tool to design finely tuned fluorescent probes, such those conceived for modern optical sensors.     

Comparing perfect and 2nd Voronoi decompositions: the matroidal locus

We compare two rational polyhedral admissible decompositions of the cone of positive definite quadratic forms: the perfect cone decomposition and the 2nd Voronoi decomposition. We determine which cones belong to both the decompositions, thus providing a positive answer to a conjecture of Alexeev and Brunyate (Invent. Math. doi:10.1007/s00222-011-0347-2, 2011). As an application, we compare the two associated toroidal compactifications of the moduli space of principal polarized abelian varieties: the perfect cone compactification and the 2nd Voronoi compactification.     

A Local Limit Theorem on Certain p-AdicGroups and Buildings

 We present a local limit theorem for a measure on the special linear group with entries in a local field. (Received 20 March 2000; in revised form 8 September 2000)     

The Molecular Basis of the Interaction of Cyclophilin A with α‐Synuclein

Peptidylprolyl isomerases (PPIases) catalyze cis/trans isomerization of prolines. The PPIase CypA colocalizes with the Parkinson's disease (PD)‐associated protein α‐synuclein in cells and interacts with α‐synuclein oligomers. Herein, we describe atomic insights into the molecular details of the α‐synuclein/CypA interaction. NMR spectroscopy shows that CypA catalyzes isomerization of proline 128 in the C‐terminal domain of α‐synuclein. Strikingly, we reveal a second CypA‐binding site formed by the hydrophobic sequence ⁴⁷GVVHGVATVA⁵⁶, termed PreNAC. The 1.38 Å crystal structure of the CypA/PreNAC complex displays a contact between alanine 53 of α‐synuclein and glutamine 111 in the catalytic pocket of CypA. Mutation of alanine 53 to glutamate, as found in patients with early‐onset PD, weakens the interaction of α‐synuclein with CypA. Our study provides high‐resolution insights into the structure of the PD‐associated protein α‐synuclein in complex with the most abundant cellular cyclophilin.     

The Effect of Temperature and Magnetic Field on the Precipitation of Insoluble Salts of Alkaline Earth Metals

Journal of Solution Chemistry - A study of the effects induced by a weak magnetic field of about 0.4&nbsp;T on the precipitation of insoluble alkaline earth carbonates is reported. Optical...     

Time domain bidirectional beam propagation method for second harmonic generation in multilayers

We propose a time domain bidirectional beam propagation method based on scattering operators for wide band pulse propagation in nonlinear multilayers. The reported numerical examples demonstrate the applicability of the algorithm for the analysis of temporal effects related to the process of second harmonic generation.     

Magneto-excitations in the rotating two-dimensional electron gas

Summary The effects of a rigid rotation on the two-dimensional electron gas are studied. For very large wavelengths the lower branch of magneto-excitations has the dispersion relationE_(k)≈[ℏΓ (ℏΓ+ve ²|k|)]^1/2 , wherev is the filling factor and Γ the angular speed of rotation. The result holds independently of the presence of a solid phase (Wigner lattice) on the gas.

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Riassunto Si studiano gli effetti di una rotazione rigida su un gas di elettroni bidimensionale. Per lunghezze d'onda molto ampie, il ramo piú basso delle eccitazioni magnetiche ha la relazione di dispersioneE_(k)≈[ℏΓ (ℏΓ+ve ²|k|)]^1/2 dovev è il fattore di riempimento e Γ la velocità angolare di rotazione. Il risultato vale indipendentemente dalla presenza di una fase solida (reticolo di Wigner) nel gas.

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Резюме Исследуется влияние жесткого вращения на двумерный электронный газ. Для очень больших длин волн низшая ветвь магнитных возбуждений имеет дисперсионное соотношениеE_(k)≈[ℏΓ (ℏΓ+ve ²|k|)]^1/2, гдеv-фактор заполнения и Γ-угловая скорость врашения. Полученный результат оказывается справедлив в присутствии твердой фазы (решетка Вигнера).