Memory effects in the NMR frequency shifts

The narrowing of the heat-bath correlation function by decreasing the sample temperature in a molecular system with a cooperative motion, causes the shifting of the NMR resonance frequency, as predicted by the memory-function approach.     

Simulation of 59Co NMR chemical shifts in aqueous solution

59Co chemical shifts were computed at the GIAO-B3LYP level for [Co(CN)6]3-, [Co(H2O)6]3+, [Co(NH3)6]3+, and [Co(CO)4]- in water. The aqueous solutions were modeled by Car-Parrinello molecular dynamics (CPMD) simulations, or by propagation on a hybrid quantum-mechanical/molecular-mechanical Born-Oppenheimer surface (QM/MM-BOMD). Mean absolute deviations from experiment obtained with these methods are on the order of 400 and 600 ppm, respectively, over a total delta(59Co) range of about 18,000 ppm. The effect of the solvent on delta(59Co) is mostly indirect, resulting primarily from substantial metal-ligand bond contractions on going from the gas phase to the bulk. The simulated solvent effects on geometries and delta(59Co) values are well reproduced by using a polarizable continuum model (PCM), based on optimization and perturbational evaluation of quantum-mechanical zero-point corrections.     

19F NMR based pH probes: lanthanide(III) complexes with pH-sensitive chemical shifts

Experimental measurements and theoretical analysis of magnetic properties, structural dynamics and acid-base equilibria for several lanthanide(III) complexes with tetraazacyclododecane derivatives as 19F NMR chemical shift pH probes are presented; pKa values vary between 6.9 and 7.7, with 18 to 40 ppm chemical shift differences between the acidic and basic forms for Ho(III) complexes possessing T1 values of 10 to 30 ms (4.7-9.4 T, 295 K).     

NMR solvent shifts of adenine in aqueous solution from hybrid QM/MM molecular dynamics simulations

We present first principles calculations of the NMR solvent shift of adenine in aqueous solution. The calculations are based on snapshots sampled from a molecular dynamics simulation, which were obtained via a hybrid quantum-mechanical/mechanical modeling approach, using an all-atom force field (TIP3P). We find that the solvation via the strongly fluctuating hydrogen bond network of water leads to nontrivial changes in the NMR spectra of the solutes regarding the ordering of the resonance lines. Although there are still sizable deviations from experiment, the overall agreement is satisfactory for the 1H and 15N NMR shifts. Our work is another step toward a realistic first-principles prediction of NMR chemical shifts in complex chemical environments.     

NMR stereotopic induced shifts in epimeric mixtures

The proton NMR spectra of epimeric mixtures of menthone ( 1 ), carvomenthone ( 2 ), carquejone ( 3 ), 2,5-dimethyl-1,4-cyclohexanedione ( 4 ) and piqueridione ( 5 ) were studied using the chemical shift reagent Eu(DPM)₃. The results allow quantifications of the epimers and some conformational assignments to be made.     

Fast determination of 13C NMR chemical shifts using artificial neural networks

Nine different artificial neural networks were trained with the spherically encoded chemical environments of more than 500000 carbon atoms to predict their 13C NMR chemical shifts. Based on these results the PC-program "C_shift" was developed which allows the calculation of the 13C NMR spectra of any proposed molecular structure consisting of the covalently bonded elements C, H, N, O, P, S and the halogens. Results were obtained with a mean deviation as low as 1.8 ppm; this accuracy is equivalent to a determination on the basis of a large database but, in a time as short as known from increment calculations, was demonstrated exemplary using the natural agent epothilone A. The artificial neural networks allow simultaneously a precise and fast prediction of a large number of 13C NMR spectra, as needed for high throughput NMR and screening of a substance or spectra libraries.     

NMR studies of lysozyme surface accessibility by using different paramagnetic relaxation probes

Paramagnetic probes, whose approach to proteins can be monitored by nuclear magnetic resonance (NMR) studies, have been found to be of primary relevance for investigating protein surfaces' accessibility. Here, a Gd(III) neutral complex which contains two metal ions, [Gd2(L7)(H2O)2], is suggested as a paramagnetic probe particularly suited for systematic NMR investigation of protein surface accessibility, due to an expected high relaxivity and to the lack of electric charge which could favor specific interactions. Hen egg white lysozyme has been used as a model system to verify the absence of preferential approaches of this paramagnetic probe to specific protein moieties by comparing paramagnetic perturbation profiles of 1H-13C HSQC signals obtained in the presence of TEMPOL and [Gd2(L7)(H2O)2]. From the similarity of the measured paramagnetic perturbation profiles induced by the two different probes, specific interactions of [Gd2(L7)(H2O)2] with the enzyme could be ruled out. The large size of the latter probe is suggested to be responsible for the strong paramagnetic perturbations observed for CalphaH groups which are located in convex surface-exposed regions. The combined use of the two probes reveals fine details of the dynamics controlling their approach toward the protein surface.     

Simple and sensitive aptamer-based colorimetric sensing of protein using unmodified gold nanoparticle probes

We describe herein simple and sensitive aptamer-based colorimetric sensing of protein (alpha-thrombin in this work) using unmodified gold nanoparticle probes.     

Naked-eye sensitive detection of nuclease activity using positively-charged gold nanoparticles as colorimetric probes

Positively-charged gold nanoparticles can effectively differentiate long DNA and fragmented DNA, thus providing a simple and visual approach to colorimetric detection of nuclease activity.     

The use of complexation induced proton NMR chemical shifts for structural analysis of host-guest complexes in solution

Proton shielding variations in supramolecular complexes contain a wealth of information on complex geometries in solution that has been until now mostly neglected. We describe herein ways for such analyses with five cyclophane and two cyclodextrin complexes in water, by using a program SHIFT which is based on and parametrized with the analyses of over 300 intramolecular proton shift variations in well defined molecular frameworks such as steroids or cyclophanes. The intermolecular shift changes in the host-guest complexes at 100% complexation (CIS values) are calculated as sum of anisotropy effects deltachi from aromatic ring currents and linear electric field effects LEF, based on force field generated geometries. The conformations with the best agreement between calculated and observed CIS values are at least for noncharged guest compounds close to those obtained from molecular mechanics and/or MD calculations and intermolecular NOEs (where available), noticeably without adjusting the complex geometries to the experimental CIS. Through-space electrostatic field effects LEF, which have been until now often neglected, can be sizeable also for noncharged systems; best agreement between experiment and calculation is observed with Gasteiger atomic charges.     

Structure-based predictions of H NMR chemical shifts of sesquiterpene lactones using neural networks

In this work the prediction of ¹H NMR chemical shifts of CH_n protons of sesquiterpene lactones by means of neural networks is described. This method is based on the incorporation of experimental chemical shifts of protons of sesquiterpene lactones as additional memory of an associative neural network system previously trained with chemical shifts of other organic compounds. One advantage of this method is its ability to distinguish between CH₂ diastereotopic protons belonging to rigid substructures since stereochemistry is considered. This is achieved via the automatic conversion of the 2D structure diagram into a 3D molecular structure. The predicted ¹H NMR chemical shifts of the sesquiterpene lactones showed a high level of accuracy. This is the first report on a fully automatic proton assignment of structures of sesquiterpene lactones of an accuracy that allows its use in structure elucidation.     

Conformations and 13C NMR shifts in tetralins

Force field (MM2) calculations, ¹³C NMR substituent-induced shifts (SIS) and epimeric shift differences (ESD) indicate a preference for equatorial substituents in the 2-position, but equal eq/ax populations in the 1-position of tetralines. Similar conclusions are reached from Yb(fod)₃-induced shifts, which are also used for signal assignments, e.g. in 1-tetralone. Configurational assignments are possible for 1,2- and 1,3-epimers (ESD up to 4 ppm) but, in line with the non-discriminating eq/ax conformations at C-I, not for 1,4-epimers (ESD<0.5 ppm). More than 50 compounds were measured, including functional derivatives which show regular SIS for substituents in the aromatic moiety only for m- and p-carbon atoms. OMe, but not OH or OAc substituents, induce o-carbon SIS varying from ?11 to ?19 ppm. Conversion of 1-hydroxytetralin to esters induces shielding variations at the aromatic carbon atoms which indicate the electrostatic origin of derivatization shifts.     

Lanthanide-induced shifts in proton NMR spectra of cyclohexanones

The lanthanide-induced shifts (LIS) of the lanthanide shift reagent (LSR) Eu(FOD)₃ are reported for a large number of cyclohexanones, especially those which are highly substituted. The following compounds were synthesized and characterized: 3-(aryl)-3,5,5-trimethylcyclohexanones, in which aryl = 1-naphthyl, phenyl, o-anisyl, m-anisyl, p-anisyl and p-chlorophenyl. Some analogous compounds were also studied: 3,5,5-trimethylcyclohexanone, 4-tert-butyl-cyclohexanone, 3,3,5,5-tetramethylcyclohexanone 3-(1-naphthyl)5,5-dimethylcyclohexanone and para-tert-butyl-anisole. A method for the regression analysis of the concentration dependence of the LIS of these substrates is developed and reported, and used to derive the limiting incremental LIS (Δ₂) for the LS₂ complex and to evaluate the proton chemical shifts (δ₀) in the absence of LSR. An ‘incremental dilution’ technique was found to be most appropriate to insure constant substrate concentrations, needed to extract both Δ₂ and δ₀. The conformations of the 3-(aryl)-type systems and analogous compounds were studied via LIS and found to conform to:—(i) an axially disposed aryl substituent in the 3,3,5,5-tetra-substituted cyclohexanones and (ii) a flattened chair form of the cyclohexanone ring with distortions in this chair form being an increase in the syn-diaxial (C-3, C-5) substituent distance (C-3 and C-5 substituents still eclipsed). The LIS were fully compatible with these structural assumptions.     

Theoretical studies on NMR chemical shifts in azacubanes

Successive substitution of CH groups of cubane (CH)(8), by isoelectronic nitrogen atoms leads to a class of energy-rich azacubanes (CH)(8-alpha)N(alpha) (with alpha=1-8). In the present work, we systematically investigate how substitution of nitrogen in a cubanoid influence deshielding of carbon and manifest in the chemical shift in NMR spectra calculated using the second order M?ller-Plesset (MP2) perturbation level of theory. PMR spectra predict a large downshift of delta(H)=7.9 ppm in heptaazacubane owing to the more number of nitrogen and the stronger C-H...N interactions. These chemical shifts are explained by the net atomic charges derived from the population analysis based on Hirshfeld partitioning scheme.