Ambient temperature 1H/13C NMR spectra of sodium 3-(trimethylsilyl)propane-1-sulfonate (DSS) in D2O referenced to external TMS: A discussion of these and closely related results. Corrections for the bulk magnetic susceptibility effect for aqueous NMR samples.

This study aimed to obtain the title spectra and verify the temperature dependence of δDSS of the HOD signal from D2O of the NMR sample. However, the analysis of the collected δX data, extended by the results of other closely related measurements reported in the literature, provided important guidelines for performing routine 1H/13C NMR spectra in aqueous solvents externally referenced to neat liquid TMS contained in a coaxial capillary. Therefore, it is recommended that the previously proposed correction of δX data thus determined, which is mainly due to the difference in volume magnetic susceptibility χv between the sample and the external standard used, usually called the bulk magnetic susceptibility (BMS) correction, has been increased by +0.05 ppm (7%). The new value of this correction, +0.73 ppm, based on NMR experiments carried out at a standard temperature of 25°C, was confirmed in a classical approach using critically reviewed χm, χM, and ρ data for TMS, D2O, and H2O. The BMS correction for H2O solutions is +0.75 ppm. Important issues concerning magnetic susceptibility measurements for D2O and H2O, coaxial bulb-ended inserts, and the geometry of two-tube NMR cells (shape factor αav) are also critically discussed here, partly from a historical perspective.

On the Use of Deuterated Organic Solvents without TMS to Report 1H/13C NMR Spectral Data of Organic Compounds: Current State of the Method, Its Pitfalls and Benefits, and Related Issues.

The quite popular, simple but imperfect method of referencing NMR spectra to residual 1H and 13C signals of TMS-free deuterated organic solvents (referred to as Method A) is critically discussed for six commonly used NMR solvents with respect to their δH and δC values that exist in the literature. Taking into account the most reliable data, it was possible to recommend 'best' δX values for such secondary internal standards. The position of these reference points on the δ scale strongly depends on the concentration and type of analyte under study and the solvent medium used. For some solvents, chemically induced shifts (CISs) of residual 1H lines were considered, also taking into account the formation of 1:1 molecular complexes (for CDCl3). Typical potential errors that can occur as a result of improper application of Method A are considered in detail. An overview of all found δX values adopted by users of this method revealed a discrepancy of up to 1.9 ppm in δC reported for CDCl3, most likely caused by the CIS mentioned above. The drawbacks of Method A are discussed in relation to the classical use of an internal standard (Method B), two 'instrumental' schemes in which Method A is often implicitly applied, that is, the default Method C using 2H lock frequencies and Method D based on Ξ values, recommended by the IUPAC but only occasionally used for 1H/13C spectra, and external referencing (Method E). Analysis of current needs and opportunities for NMR spectrometers led to the conclusion that, for the most accurate application of Method A, it is necessary to (a) use dilute solutions in a single NMR solvent and (b) to report δX data applied for the reference 1H/13C signals to the nearest 0.001/0.01 ppm to ensure the precise characterization of new synthesized or isolated organic systems, especially those with complex or unexpected structures. However, the use of TMS in Method B is strongly recommended in all such cases.

Unexpected Rearrangement of Dilithiated Isoindoline-1,3-diols into 3-Aminoindan-1-ones via N-Lithioaminoarylcarbenes: A Combined Synthetic and Computational Study.

The reaction of 2-aryl-3-hydroxyisoindolin-1-ones with the s-BuLi·TMEDA system in THF at -78 °C, affording a series of diastereomeric 3-aminoindan-1-ones via a novel rearrangement of the isoindolinone scaffold, is reported. It is proposed that α-elimination of LiOH from the transient N,O-dilithiated hemiaminal carbenoids leads to the formation of singlet carbenes followed by their trapping via an intramolecular C-H insertion. An alternative explanation based on an intramolecular Mannich reaction seem much less probable. A mechanistic-type study that combines spectroscopic data of the products and calculation results, with a special focus on the diverse lithiated intermediates that are most likely to engage in the title process (particularly those with internal Li bonds), is presented. The MP2 approach, including the NPA and QTAIM data, provided insight into structures and properties of all these species. Two reaction routes A and B appeared to be possible for the postulated carbene mechanism. An unusual metamorphosis of the CCN atom triad, from a near sp 1-azaallene-type in more stable noncarbene Li enolates to a roughly sp2 type in their carbene keto tautomers, is recognized in one of these pathways (route B). Dominant forms of resonance structures for the aforementioned tautomeric systems that have seven-membered quasi rings stabilized by Li+ ions bridging the N and carbonyl O atoms are indicated. Large computational difficulties arising from a huge impact of internal Li+ complexation on conformational preferences and electronic properties of carbonyl group-bearing lithium derivatives are also discussed. The new γ-keto carbene species under study belong to a subclass of acyclic aminoarylcarbenes.

Shortfall of B3LYP in Reproducing NMR JCH Couplings in Some Isomeric Epoxy Structures with Strong Stereoelectronic Effects: A Benchmark Study on DFT Functionals.

Unprecedented scatter plots of calculated versus measured NMR 2,3 JCH coupling constants in six densely oxygen functionalized epoxides are found with some B3LYP protocols, an effect attributed to stereoelectronic effects. Hence, 26 other exchange-correlation density functionals (xc DFs) are benchmarked in this work. Very good results are achieved with mPW1PW91 and PBE0 in conjunction with the pcJ-1 basis set (BS) of moderate size. A thorough statistical analysis of 53 relationships between the predicted and observed 2,3 JCH datasets is presented. The effects of some xc DFs, including their x and c parts, and BSs on the calculation results are discussed, also in the context of DFT modeling of electron-density distributions. Moreover, related 1 JCH datasets predicted with 11 different DF methods are considered and compared with the experimental data. Finally, some proposals for further improvement of existing DFs based on the available n JCH (n=1-3) values are briefly outlined, in line with recent results on the DFT electron densities.

A Benefit of Using the IDSCRF- over UFF-Radii Cavities and Why Joint Correlations of NMR Chemical Shifts Can Be Advantageous: Condensed Pyridines as an IEF-PCM/GIAO/DFT Case Study.

Herein, an advantage of the use of IDSCRF- over UFF-radii-based solute cavities in GIAO/DFT calculations is presented for the 13C and especially 15N NMR chemical shifts made for several bicyclic aromatic nitrogen heterocycles in CDCl3 solution treated within the classical IEF-PCM solvation scheme. Successful application of the IDSCRF-radii in the non 1:1 joint multinuclear 1H/13C and particularly 1H/13C/15N correlations of the measured δH,C(,N) values to those obtained theoretically is also documented for a series of test systems (-268 ≤ δN ≤ -72 ppm). The experimentally yet unknown δN's were found in this way for the title compounds via a trinuclear eq 1 determined for an optimally chosen value of the multiplication factor of initial raw δH data (mH = 10). Such a simultaneous analysis of the δH,C(,N) data is proposed as a novel method to study the solution structure of the other similar conformationally homogeneous (bio)organic compounds. The issue of small spurious imaginary vibrational frequencies computed for a few molecular systems using the Gaussian 09 default UFF-radii is briefly considered as well.

Multi-conformer molecules in solutions: an NMR-based DFT/MP2 conformational study of two glucopyranosides of a vitamin E model compound.

Overall conformations of both anomeric per-O-acetylated glucosyl derivatives of 2,2,5,7,8-pentamethylchroman-6-ol were studied in the context of their high flexibility, on the basis of NMR spectra in CDCl3 solution and related DFT calculation results. A few computational protocols were used, including diverse density functional/basis set combinations with a special emphasis on accounting (at various steps of the study) for the impact of intramolecular London-dispersion (LD) effects on geometries and relative Gibbs free energies (ΔGs) of different conformers coexisting in solution. The solvent effect was simulated by an IEF-PCM approach with the UFF radii; its other variants, including the use of the recently introduced IDSCRF radii, were employed for a few compact B3LYP-GD3BJ optimized structures showing one small imaginary vibrational frequency. The advantage of using IDSCRF radii for such purposes was shown. Of the four tested DFT methods, only the application of the B3LYP/6-31+G(d,p) approximation afforded ensembles of 7-8 single forms for which population-average values of computed NMR parameters (δH, δC and some (n)JHH data) were in close agreement with those measured experimentally; binuclear (δH,C 1 : 1) correlations, rH,C(2) = 0.9998. The associated individual ΔG values, corrected for LD interactions by applying Grimme's DFT-D3 terms, afforded relative contents of different contributors to the analyzed conformational families in much better agreement with pertinent DFT/NMR-derived populations (i.e., both data sets were found to be practically equal within the limits of estimated errors) than those calculated from dispersion uncorrected ΔGs. All these main findings were confirmed by additional results obtained at the MP2 level of theory. Various other aspects of the study such as the crystal vs. solution structure, gg/gt rotamer ratio, diagnostic (de)shielding effects, dihydrogen C-H···H-C contacts, and doubtful applicability of some specialized DFT functionals (M06-2X, ωB97X-D and B3LYP-GD3BJ) for the description of highly flexible molecules are also discussed in detail.

¹J(CH) couplings in Group 14/IVA tetramethyls from the gas-phase NMR and DFT structural study: a search for the best computational protocol.

Four tetramethyl compounds EMe4 (E = C, Si, Ge, and Pb) were studied by high-resolution NMR spectroscopy in gaseous and liquid states at 300 K. Extrapolation of experimental vapor-phase C-H J-couplings to a zero-pressure limit permitted determining the (1)J(0,CH)s in methyl groups of their nearly isolated molecules. Theoretical predictions of the latter NMR parameters were also performed in a locally dense basis sets/pseudopotential (Sn, Pb) approach, by applying a few DFT methods pre-selected in calculations of other gas-phase molecular properties of all these species and SnMe4 (bond lengths, C-H stretching IR vibrations). A very good agreement theory vs. experiment was achieved with some computational protocols for all five systems. The trends observed in their geometry and associated coupling constants ((1)J(CH)s, (2)J(HH)s) are discussed and rationalized in terms of the substituent-induced rehybridization of the methyl group (treated as a ligand) carbon, by using Bent's rule and the newly proposed, theoretically derived values of the Mulliken electronegativity (χ) of related atoms and groups. All these χ data for the Group-14/IVA entities were under a lot of controversy for a very long time. As a result, the recommended χ values are semi-experimentally confirmed for the first time and only a small correction is suggested for χ(Ge) and χ(GeMe3).

13C longitudinal relaxation time measurements and DFT-GIAO NMR computations for two ammonium ions of a tetraazamacrocyclic scorpiand system.

ABSTRACT: Spin-lattice relaxation times, T1s, for 13C nuclei in two cations H n1n+ (n = 1, 5) of N-(2-aminoethyl)-cyclam (1, scorpiand) were determined by means of 13C{1H} NMR experiments in aqueous solution at pH 11.5 and 0.2. The theoretical study [modeling with OPLS-AA, B3LYP/6-31G(d) geometry optimizations, dispersion-corrected energies (DFT-D3), and DFT-GIAO predictions of the NMR chemical shifts (including an IEF-PCM simulation of hydration)] was also done for several conformers of the tautomer iso-H414+ not investigated before. The binding directions in protonated polyamino receptors necessary for efficient complexation of the nitrate anion(s) were briefly outlined, as well. All these results were discussed in terms of 'abnormal' 13C chemical shift changes found previously for the side-chain carbons of amine 1 in strongly acidic solution (HNO3). In conclusion, an earlier proposal of its association with NO3- at pH <1 was rejected. Instead, the participation of small amounts of a micro-species iso-H414+Dhydr under such conditions can be proposed. GRAPHICAL ABSTRACT: A small contribution of iso-H414+Dhydr (see figure) to an ionic mixture of pentamine 1 was proposed to explain the 'abnormal' 13C NMR shifts observed for atoms C11 and C12 in its side-chain arm, at pH <1.

Sucrose transport is inhibited by okadaic acid during regeneration of sugar-starved Vicia faba root meristem cells.

The sucrose-induced resumption of cell cycle in the Vicia faba root meristem cells, blocked in two principal control points PCP1/2 by carbohydrate starvation, occurs after 12 h of metabolic regeneration comprising increased activity of sucrose synthase (SuSy) and hexokinase (HK) as well as starch grain and cell wall matrix polysaccharide biosynthesis. Okadaic acid (OA), the specific protein phosphatase 1/2A inhibitor, supplied at the beginning of the recovery period (0-3 h) completely blocks these processes, making cell cycle resumption impossible. On the other hand, when added at the end (9-12 h), OA has a weak inhibitory effect. The aim of these studies was: (1) to establish how sucrose is transported into the cells and whether the above-mentioned effects are correlated with the intensity of its uptake at the beginning and at the end of the metabolic regeneration; and (2) to determine whether OA, blocking sucrose metabolism, also interferes with the process of sucrose uptake and distribution. The level of [(3)H]sucrose uptake was measured by liquid scintillation counting while sugar distribution was analyzed using microautoradiography and electron microscopy. The results showed that sucrose entered the meristematic cells along symplastic or apoplastic pathways and, to a lesser extent, through endocytosis. The cytoplasmic compartments (endoplasmic reticulum, vacuoles, plastids) and the nucleus were labeled. The intensity of [(3)H]sucrose uptake was nearly 2-fold lower during the initial than during the final period of metabolic regeneration. OA inhibited the apoplastic pathway of radioactive molecule uptake and its distribution between cell compartments, implicating PP1/2A involvement in the regulation of this transport.

Synthesis and biological evaluation of new bischromone derivatives with antiproliferative activity.

The synthesis of new bischromone derivatives (4a-c and 5a-c) as potential anticancer drugs is described. The difference in the reactivity between 4-oxo-4H-chromene-3-carboxylic acid 2 (or its methyl ester 3) and 4-oxo-4H-chromene-3-carbonyl chloride 1 with three different polyamines: 3,3'-diamino-N-methyldipropylamine (a), 1,4-bis(3-aminopropyl)piperazine (b), 4,9-dioxa-1,12-dodecanediamine (c) resulted in the formation of two different groups of products, compounds 4a-c and 5a-c, designed in agreement with the bisintercalators' structural requirements. The transformation of 4-oxo-4H-chromene-3-carboxylic acid into 2H-chromene-2,4(3H)-diones (5) was confirmed by the NMR and XRD experiments. Compounds 4a and 5a were evaluated in vitro in the highly aggressive melanoma cell line A375. An enhanced induction of apoptosis and cell cycle arrest clearly revealed that compound 5a was more potent than 4a. Compound 5a was also more active in diminishing the adhesive potential of melanoma cells. Current studies support the notion that small changes in the three-dimensional structure of molecules might have a substantial impact on their biological activity.