To find and calibrate a robust and reliable computational protocol for mapping conformational space of medium-sized molecules, exhaustive conformational sampling has been carried out for a series of seven macrocyclic compounds of varying ring size and one acyclic analogue. While five of them were taken from the MD/LLMOD/force field study by Shelley and co-workers ( Watts , K. S. ; Dalal , P. ; Tebben , A. J. ; Cheney , D. L. ; Shelley , J. C. Macrocycle Conformational Sampling with MacroModel . J. Chem. Inf. MODEL: 2014 , 54 , 2680 - 2696 ), three represent potential macrocyclic inhibitors of human cyclophilin A. The free energy values (GDFT/COSMO-RS) for all of the conformers of each compound were obtained by a composite protocol based on in vacuo quantum mechanics (DFT-D3 method in a large basis set), standard gas-phase thermodynamics, and the COSMO-RS solvation model. The GDFT/COSMO-RS values were used as the reference for evaluating the performance of conformational sampling algorithms: standard and extended MD/LLMOD search (simulated-annealing molecular dynamics with low-lying eigenvector following algorithms, employing the OPLS2005 force field plus GBSA solvation) available in MacroModel and plain molecular dynamics (MD) sampling at high temperature (1000 K) using the semiempirical quantum mechanics (SQM) potential SQM(PM6-D3H4/COSMO) followed by energy minimization of the snapshots. It has been shown that the former protocol (MD/LLMOD) may provide a more complete set of initial structures that ultimately leads to the identification of a greater number of low-energy conformers (as assessed by GDFT/COSMO-RS) than the latter (i.e., plain SQM MD). The CPU time needed to fully evaluate one medium-sized compound (∼100 atoms, typically resulting in several hundred or a few thousand conformers generated and treated quantum-mechanically) is approximately 1,000-100,000 CPU hours on today's computers, which transforms to 1-7 days on a small-sized computer cluster with a few hundred CPUs. Finally, our data sets based on the rigorous quantum-chemical approach allow us to formulate a composite conformational sampling protocol with multiple checkpoints and truncation of redundant structural data that offers superior insights at affordable computational cost.
- MeSH
- algoritmy MeSH
- kalibrace MeSH
- krystalografie MeSH
- kvantová teorie MeSH
- makrocyklické sloučeniny chemie MeSH
- molekulární konformace * MeSH
- rychlé screeningové testy MeSH
- simulace molekulární dynamiky MeSH
- termodynamika MeSH
- vysoká teplota MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
A synthesis procedure for heteroatom-substituted tetra(3,4-pyrido)porphyrazines that absorb light near 800 nm was developed. Based on the observed relationships between the structure and photophysical parameters, a novel highly photodynamically active (IC50 = 0.26 μM) compound was synthesized and biologically characterized.
In many bioanalytical applications, important molecules such as DNA, proteins, and antibodies are routinely conjugated with fluorescent tags to reach an extraordinary sensitivity of analyses. Semiconductor nanoparticles, quantum dots, have already proved to be suitable components of highly luminescent tags, probes, and sensors with a broad applicability in analytical chemistry. Quantum dots provide high extinction coefficients together with a wide range of excitation wavelengths, size- and composition-tunable emissions, narrow and symmetric emission spectra, good quantum yields, relatively long size-dependent luminescence lifetime, and practically no photobleaching. Most of these properties are superior when compared with conventional organic fluorescent dyes. In this chapter, optimized procedures for the preparation of water-dispersed cadmium telluride (CdTe) quantum dots, conjugating reactions with antibodies, DNA, and macrocycles as well as their analyses by capillary electrophoresis are described. The potential of capillary electrophoresis for fast analyses of nanoparticles, their conjugates with antibodies, and immunocomplexes with targeted antigens is demonstrated on examples.
- MeSH
- DNA analýza chemie MeSH
- elektroforéza kapilární přístrojové vybavení metody MeSH
- imunoanalýza MeSH
- kvantové tečky analýza chemie MeSH
- lasery * MeSH
- luminiscenční měření metody MeSH
- makrocyklické sloučeniny chemie MeSH
- polovodiče MeSH
- rezonanční přenos fluorescenční energie MeSH
- sloučeniny kadmia chemie MeSH
- telur chemie MeSH
- voda chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Lanthanide(III) complexes of 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (H(3)DO3A) are suggested as sensors for sensitive luminescence-based determination of a carbonate anion. Thermodynamic study of association of [Eu(H(2)O)(2)(DO3A)] with bidentate anionic ligands using luminescence spectroscopy reveals an affinity order CO(3)(2-) > oxalate(2-) > picolinate(-) > phthalate(2-) ≈ citrate(3-); presumably as a consequence of an increasing chelate ring size. The ternary [Eu(DO3A)(picolinate)](-) and [Tb(DO3A)(picolinate)](-) complexes show improved photophysical properties due to the antenna effect of the picolinate anion. High quenching effect of carbonate anion and, to a lesser extent also oxalate, enables construction of a linear calibration plot utilizing optimized experimental conditions (e.g. c(LnL) = 0.1 mM, c(picolinate) = 2-5 mM, pH = 7.4, λ(exc) = 286 nm, etc.) for carbonate determination in solution. Both sensors show a comparable sensitivity and the detection limit of about 0.4 mM. In order to improve the photophysical properties of Ln(III) sensor by shift of excitation wavelength about 40 nm to VIS range, the isoquinoline-3-carboxylic acid (IQCA) as antenna ligand was employed instead of picolinic acid. The analysis of commercial samples of European mineral waters was carried out and they were compared to the results obtained by capillary isotachophoresis to confirm there is no inherent (systematic) error to the present analysis. The Ln(III) sensor with IQCA is recommended since it has a better robustness than that with picolinate. The present analytical method is simple and rapid, and it is useful for sensitive determination of bicarbonate/carbonate concentration in water samples under aerobic conditions.
- MeSH
- chemické techniky analytické přístrojové vybavení MeSH
- europium chemie MeSH
- heterocyklické sloučeniny monocyklické chemie MeSH
- ligandy MeSH
- luminiscenční měření MeSH
- makrocyklické sloučeniny chemie MeSH
- organokovové sloučeniny chemie MeSH
- terbium chemie MeSH
- termodynamika MeSH
- uhličitany analýza chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Anion recognition plays an important role in many areas of the natural world. Macrocyclic anion receptors and their potentials are outlined. Bambusurils, a family of glycoluril-based anion receptors, are described in detail.
elektronický časopis
- Konspekt
- Biochemie. Molekulární biologie. Biofyzika
- NLK Obory
- biochemie
- biologie
- NLK Publikační typ
- elektronické časopisy
