Evaluation of the intramolecular basis set superposition error in the calculations of larger molecules: [n]helicenes and Phe-Gly-Phe tripeptide

Correlated ab initio calculations on large systems, such as the popular MP2 (or RI-MP2) method, suffer from the intramolecular basis set superposition error (BSSE). This error is typically manifested in molecules with folded structures, characterized by intramolecular dispersion interactions. It can dramatically affect the energy differences between various conformers as well as intramolecular stabilities, and it can even impair the accuracy of the predictions of the equilibrium molecular structures. In this study, we will present two extreme cases of intramolecular BSSE, the internal stability of [n]helicene molecules and the relative energies of various conformers of phenylalanyl-glycyl-phenylalanine tripeptide (Phe-Gly-Phe), and compare the calculated data with benchmark values (experimental or high-level theoretical data). As a practical and cheap solution to the accurate treatment of the systems with large anticipated value of intramolecular BSSE, the recently developed density functional method augmented with an empirical dispersion term (DFT-D) is proposed and shown to provide very good results in both of the above described representative cases.     

Ab initio benchmark calculations on Ca(II) complexes and assessment of density functional theory methodologies

A set of benchmark results for the geometries, binding energies, and protonation affinities of 24 complexes of small organic ligands with Ca(II) is provided. The chosen level of theory is CCSD(T)/CBS obtained by means of a composite procedure. The performance of four density functionals, namely, PW91, PBE, B3LYP, and TPSS and several Pople-type basis sets, namely, 6-31G(d), 6-31+G(d), 6-31+G(2d,p) and 6-311+G(d) have been assessed. Additionally, the nature of the metal ligand bonding has been analyzed by means of the Symmetry Adapted Perturbation Theory (SAPT). We have found that the B3LYP hybrid functional, in conjunction with either the polarized double-ζ 6-31+G(2d,p) or the triple-ζ 6-311+G(d) basis sets, yields the closest results compared to the benchmark data. The SAPT analysis stresses the importance of induction effects in the binding of these complexes and suggests that consideration of classical electrostatic contributions alone may not be reliable enough for the prediction of relative binding energies for Ca(II) complexes.     

Density-functional, density-functional tight-binding, and wave function calculations on biomolecular systems

Recently, two computational approaches that supply a density-functional-based quantum-chemical method with an empirical term accounting for London dispersion were introduced and found use in the studies of biomolecular systems, namely, DFT-D and SCC-DFTB-D. Here, we examine the performance and usability of these combined techniques for dealing with several tasks typically occurring in the research of biomolecules. The interaction energy of small biomolecular complexes agrees very well with the reference data yielded by correlated ab initio quantum chemical methods. In real-life studies aimed at interaction energy, structure, and infrared spectra, the mentioned methods provide results in good agreement with each other and with experiment (where available). The very favorable time demands of these approaches are discussed, and for each of them, a suitable area of use is proposed on the basis of the results of our analysis.     

Sensitivity to ALA-PDT of cell lines with different nitric oxide production and resistance to NO cytotoxicity

In this work, we studied the in vitro interactions between aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) and nitric oxide (NO), as well as the interactions between ALA, porphyrins and some NO donors and precursors. We employed three murine adenocarcinoma cell lines: LM2, which does not produce NO; LM3, which produces NO, and LM3-SNP, a variant of LM3 resistant to NO producing the same amount of NO as the parental. We did not find cross-resistance between NO-induced cytotoxicity and ALA-PDT. In spite of the lower porphyrin synthesis, LM2 cells show the highest sensitivity to ALA-PDT. However, we hypothesised that this is not related to the lack of endogenous NO production, because modulation of NO levels did not modify the response to PDT in any of the cell lines.

Two unexpected results were found: the enhancement of NO production from the donor sodium nitroprusside (SNP) induced by ALA in both cells and medium, and the inhibition by ALA of NO production from arginine. We also found that SNP strongly protected the cells from ALA-PDT by impairing porphyrin biosynthesis as a consequence of an inhibition of the enzyme ALA dehydratase. We were not able to evaluate the action of NO derived from SNP because of the unexpected porphyrin impairment. On the other hand, impairment of NO from Arginine driven by ALA, although not modulating in vitro the ALA-PDT response, by increasing in vivo blood flow, may be contributing to the mechanism of tumour cures.     

Characterisation of liposomes containing aminolevulinic acid and derived esters

Liposomes of different compositions have been designed to improve delivery of aminolevulinic acid (ALA) and its esterified derivatives ALA-Hexyl ester (He-ALA) and ALA-Undecanoyl ester (Und-ALA) for its use in photodynamic therapy (PDT). Egg yolk phosphatidyl choline (PC), phosphatidic acid (PA) and phosphatidyl glycerol (PG) were employed in the preparation of the liposomes. Sonicated vesicles composed of PC, PC-PG (80:20) or PC-PA (80:20) containing ALA or derivatives were obtained and purified by a minicolumn centrifugation method. PC liposomes presented encapsulation percentages around 6% for 2 mM ALA, 13% for 2 mM He-ALA and 51% for 2 mM Und-ALA. The addition of PG or PA to the formulation, resulted in an increased entrapment: 19% for 2 mM ALA, 69% for 2 mM He-ALA and 87% for 2 mM Und-ALA in PC-PG liposomes and 21% for 2 mM ALA, 60% for 2 mM He-ALA and 87% for 2 mM Und-ALA in PC-PA liposomes. Higher concentrations of ALA or derivatives resulted in lower percentages of entrapment. The three formulations containing ALA or derivatives were stable up to 1 week upon storage at 4 degrees C. However, upon dilution with medium, ALA leaked from the liposomes, while on the contrary, He-ALA was highly retained, being therefore a good choice for its use in PDT. The stability of Und-ALA upon dilution could not be tested, but Und-ALA proved to have the highest entrapment efficacy.     

The interaction of the easily polarizable hydrogen bonds with phonons and polaritons of the thermal bath-far infrared continua

B⁺HBBH⁺B or AHB⁻AH⁺B hydrogen bonds, respectively, with double minimum proton potential well or broad flat potential well cause continuous absorptions in the infrared spectra. The intensity of these infrared continua is often very large, i.e. their integrated intensity is much larger than that of infrared bands. Short strong hydrogen bonds with broad flat in the average largely symmetrical proton potentials in which the protons fluctuate, show so-called proton polarizabilities. With such systems, the infrared continua extend in the far infrared region, i.e. in the region below 600 cm⁻¹. It is, however known that with such bonds no proton transitions occur in this region.

It is demonstrated that the intensity of these infrared continuous absorptions is strongly increased by the coupling of the hydrogen bonds with large proton polarizability with the phonons of the thermal bath around these hydrogen bonds. Further, it is demonstrated that the pronounced absorption in the far infrared region, i.e. the region below 600 cm⁻¹, occurs due to the strong coupling of these hydrogen bonds to the polaritons. The polaritons are the quanta of the thermal bath coupled to the phonons of the thermal bath.     

A method for separating ALA from ALA derivatives using ionic exchange extraction

Photodynamic therapy using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX is a recent approach to detect and treat some malignancies. The use of lipophilic derivatives of ALA has been exploited in the last years to enhance ALA penetration. In this paper, we describe the application of the Mauzerall and Granick's method [J. Biol. Chem. 219 (1956) 435] to the quantification of ALA derivatives. We also describe the employment of reusable ion-exchange chromatographic columns for separating mixtures of ALA and ALA derivatives present in biological samples. The relation between 555 nm absorbance and ALA or ALA derivative concentration was linear up to 100 nmol/ml and the limit of detection of ALA and ALA derivatives was 1 nmol per ml. We employed a Dowex 50 X8 hydrogen form resin to separate ALA from the derivatives. Whereas 90+/-4% of the total ALA was eluted using sodium acetate, only 3-9% of the ALA derivatives was recovered. Only upon exposure of the resin to a high HCl concentration, the ALA derivatives were completely released. We employed this new method for the separation of ALA from ALA derivatives in cells exposed to different ALA compounds.     

Resolution of identity density functional theory augmented with an empirical dispersion term (RI-DFT-D): a promising tool for studying isolated small peptides

Resolution of identity standard density functional theory augmented with a damped empirical dispersion term (RI-DFT-D) calculations have been carried out on a set of lowest energy minima of tryptophyl-glycine (Trp-Gly) and tryptophyl-glycyl-glycine (Trp-Gly-Gly) peptides. RI-DFT-D (TPSS/TZVP) results are in excellent agreement with benchmark data based on the CCSD(T) method. Experimental spectra could be assigned according to the calculated IR frequencies. Central processing unit (CPU) time requirements are only slightly higher than those needed for the DFT calculations. Consequently, RI-DFT-D theory seems to be a promising methodology for studying oligopeptides with accuracy comparable to ab initio quantum chemical calculations.     

New open-book decompositions in singularity theory

In this article, we study the topology of real analytic germs ${F \colon (\mathbb{C}^3,0) \to (\mathbb{C},0)}$ given by ${F(x,y,z)=\overline{xy}(x^p+y^q)+z^r}$ with ${p,q,r \in \mathbb{N}, p,q,r \geq 2}$ and (p, q)?=?1. Such a germ gives rise to a Milnor fibration ${\frac{F}{\mid F \mid}\colon \mathbb{S}^5\setminus L_F \to \mathbb{S}^1}$ . We describe the link L _F as a Seifert manifold and we show that in many cases the open-book decomposition of ${\mathbb{S}^5}$ given by the Milnor fibration of F cannot come from the Milnor fibration of a complex singularity in ${\mathbb{C}^3}$ .