Spatially encoded pure-shift diffusion-ordered NMR spectroscopy yielded by chirp excitation.

Spatially-encoded diffusion-ordered NMR spectroscopy (SPEN-DOSY) has emerged as a new time-efficient tool for the analysis of mixtures of small molecules in solution. Time efficiency is achieved using the concept of spatial parallelization of the effective gradient area, instead of the sequential incrementation used in conventional diffusion experiments. The data acquired with such sequences are then usually processed to extract diffusion coefficients, but cases when peak overlap in the 1H spectrum are difficult to address. Such limitation in conventional diffusion experiments is addressed via using the Pure Shift Yielded by CHirp Excitation (PSYCHE)-iDOSY sequence. Here we have adapted the PSYCHE-iDOSY sequence by using echo planar spectroscopic imaging (EPSI) to acquire SPEN-DOSY data. The pure shift mode of PSYCHE separates the overlapped components and a modified Stejskal-Tanner equation is used to extract the corresponding diffusion coefficient. The primary results obtained with the above-mentioned mixtures seem to open the possibility of separating complex mixtures in less time than PSYCHE-iDOSY.

Adaptive optimal control of entangled qubits.

Developing fast, robust, and accurate methods for optimal control of quantum systems comprising interacting particles is one of the most active areas of current science. Although a valuable repository of algorithms is available for numerical applications in quantum control, the high computational cost is somewhat overlooked. Here, we present a fast and accurate optimal control algorithm for systems of interacting qubits, QOALA (quantum optimal control by adaptive low-cost algorithm), which is predicted to offer [Formula: see text](M2) speedup for an M-qubit system, compared to the state-of-the-art exact methods, without compromising overall accuracy of the optimal solution. The method is general and compatible with diverse Hamiltonian structures. The proposed approach uses inexpensive low-accuracy approximations of propagators far from the optimum, adaptively switching to higher accuracy, higher-cost propagators when approaching the optimum. In addition, the utilization of analytical Lie algebraic derivatives that do not require computationally expensive matrix exponential brings even better performance.

Towards fully optimised and automated ESR spectroscopy.

To address the problems of instrumental imperfection and time-consuming experimental setup in electron spin resonance (ESR), we present ESR-POISE, a user-friendly software package for fully automated and fast on-the-fly optimisation and acquisition of ESR experiments. This open-source package interfaces with Bruker's Xepr software and allows scientists to run user-defined optimisations.

Newton meets Ockham: Parameter estimation and model selection of NMR data with NMR-EsPy.

We present NMR-EsPy (NMR Estimation in Python), a versatile, simple-to-use Python package for estimating the signal parameters that describe one-dimensional time-domain NMR data. The software is fully integrated into Topspin, a widely used NMR platform, and comes with a Graphical User Interface, allowing users unfamiliar with the underlying theory and/or Python programming to access the full functionality of the software package. NMR-EsPy utilises Newton's method, an iterative non-linear programming technique. By including the variance of oscillator phases in the optimization, NMR-EsPy can generate parsimonious parameter estimates, giving NMR users access to meaningful quantitative information. This principle is easily extendable to study specific regions of an NMR spectrum to reduce computational cost. The complete mathematical treatment along with examples of the implementation of the estimation routine are presented.

Improved design of frequency-swept pulse sequences.

Frequency-swept pulses are extensively used in magnetic resonance spectroscopic techniques for the robust manipulation of spins across wide ranges of offset frequencies in the presence of B1 field variations. Nevertheless, designing pulse sequences consisting of multiple frequency-swept pulses can be challenging, as they often require specific timings and parameter tweaking. In the present work we discuss a simple and general approach for constructing such sequences. We present new and improved pulse sequences for applications including broadband B1-tolerant CPMG (CHORUS-CPMG), broadband chirped excitation with suppression of homonuclear J-modulation (PROCHORUS), and the further compression of frequency-swept pulse sequences by superposition of pulses which reduces pulse sequence durations by 25-40%. All sequence design strategies are accompanied by mathematical presentations, experimental results, and supporting simulations.

On-the-Fly, Sample-Tailored Optimization of NMR Experiments.

NMR experiments, indispensable to chemists in many areas of research, are often run with generic, unoptimized experimental parameters. This approach makes robust and automated acquisition on different samples and instruments extremely challenging. Here, we present NMR-POISE (Parameter Optimization by Iterative Spectral Evaluation), the first demonstration of on-the-fly, sample-tailored, and fully automated optimization of a wide range of NMR experiments. We illustrate how POISE maximizes spectral sensitivity and quality with a diverse set of 1D and 2D examples, ranging from HSQC and NOESY experiments to ultrafast and pure shift techniques. Our Python implementation of POISE has an interface integrated into Bruker's TopSpin software, one of the most widely used platforms for NMR acquisition and automation, allowing NMR optimizations to be run without direct user supervision. We predict that POISE will find widespread usage in academia and industry, where sample-specific and automated experiment optimization is mandatory.

Chirped ordered pulses for ultra-broadband ESR spectroscopy.

Recently, applications of swept-frequency pulses proved to be a useful approach to circumvent the problem of limited excitation bandwidth in pulsed ESR posed by conventional pulses. Here, we present a chirped excitation sequence, CHirped ORdered pulses for Ultra-broadband Spectroscopy (CHORUS), for ultra-broadband ESR spectroscopy. It will be demonstrated that the application of this sequence can address the problems of excitation non-uniformity and sensitivity to instrumental instabilities to a greater extent compared to the current state of the art. This sequence is highly promising for finding applications beyond single excitation in many ESR experiments. Theoretical and experimental results for the proposed method are presented along with calibration strategies for experimental implementation.

Spin dynamics during chirped pulses: applications to homonuclear decoupling and broadband excitation.

Swept-frequency pulses have found applications in a wide range of areas including spectroscopic techniques where efficient control of spins is required. For many of these applications, a good understanding of the evolution of spin systems during these pulses plays a vital role, not only in describing the mechanism of techniques, but also in enabling new methodologies. In magnetic resonance spectroscopy, broadband inversion, refocusing, and excitation using these pulses are among the most used applications in NMR, ESR, MRI, and in vivo MRS. In the present survey, a general expression for chirped pulses will be introduced, and some numerical approaches to calculate the spin dynamics during chirped pulses via solutions of the well-known Liouville-von Neumann equation and the lesser-explored Wei-Norman Lie algebra along with comprehensive examples are presented. In both cases, spin state trajectories are calculated using the solution of differential equations. Additionally, applications of the proposed methods to study the spin dynamics during the PSYCHE pulse element for broadband homonuclear decoupling and the CHORUS sequence for broadband excitation will be presented.

A visible-light photoactivatable di-nuclear PtIV triazolato azido complex.

A novel PtIV triazolato azido complex [3]-[N1,N3] has been synthesised via a strain-promoted double-click reaction (SPDC) between a PtIV azido complex (1) and the Sondheimer diyne (2). Photoactivation of [3]-[N1,N3] with visible light (452 nm) in the presence of 5'-guanosine monophosphate (5'-GMP) produced both PtIV and PtII 5'-GMP species; EPR spectroscopy confirmed the production of both azidyl and hydroxyl radicals. Spin-trapping of photogenerated radicals - particularly hydroxyl radicals - was significantly reduced in the presence of 5'-GMP.

Improved ultra-broadband chirp excitation.

The design and application of ultra-broadband excitation pulses have been among the most interesting and timely areas in NMR and EPR methodology in recent years, due especially to advances in hardware design in EPR, the advent and popularity of high- and ultrahigh-field NMR, and the application of numerical methods like optimal control theory to the design and optimization of radiofrequency pulses and pulse sequences. In this communication, we present a short, robust, and flexible version of the CHORUS family of constant-phase, very broadband excitation sequences. We demonstrate that more than 0.5 MHz excitation with uniform amplitudes and phases can be achieved with this excitation sequence.

Unexploited Dimension: New Software for Mixture Analysis by 3D Diffusion-Ordered NMR Spectroscopy.

3D DOSY experiments have the potential to provide unique and valuable information, but they are underused, in part because of the lack of efficient processing software. Here, we illustrate the power of 3D DOSY and present MAGNATE, Multidimensional Analysis for the GNAT Environment, an open-source and free software package for the analysis of pulsed field gradient (PFG) 3D NMR diffusion data, distributed under the GNU General Public License. The new software makes it possible for the first time to efficiently analyze and visualize 3D diffusion (e.g., 3D HSQC-DOSY) data using both univariate (e.g., DOSY) and multivariate (e.g., OUTSCORE) methods in a user-friendly graphical interface. The software can be used either independently or as a module in the GNAT program.

Suppression of 13C satellites in 1H DOSY spectra.

Diffusion-ordered spectroscopy (DOSY) is a valuable tool for the analysis of intact mixtures, since it can separate the signals of components according to their apparent diffusion coefficients. However, DOSY experiments are acutely sensitive to spectral quality, and especially to signal overlap, which can lead to misleading apparent diffusion coefficients. Here, we introduce a new NMR experiment to reduce signal overlap in mixtures with a wide range of concentrations, by removing one-bond 13C satellites. In such high dynamic range mixtures, 13C isotopomer signals from major components can overlap with signals from minor components, causing problematic distortions in the diffusion domain of a DOSY spectrum. The new method, Oneshot-iDISPEL, is a combination of the Oneshot and DISPEL experiments, and its performance has been demonstrated on a Greek alcoholic beverage, ouzo, which contains small amounts of anise flavour components and sucrose. Ethanol is a major component, and the suppression of its 13C satellites reduces signal overlap with minor components, offering significant improvement in DOSY spectra.

PSYCHE Pure Shift NMR Spectroscopy.

Broadband homodecoupling techniques in NMR, also known as "pure shift" methods, aim to enhance spectral resolution by suppressing the effects of homonuclear coupling interactions to turn multiplet signals into singlets. Such techniques typically work by selecting a subset of "active" nuclear spins to observe, and selectively inverting the remaining, "passive", spins to reverse the effects of coupling. Pure Shift Yielded by Chirp Excitation (PSYCHE) is one such method; it is relatively recent, but has already been successfully implemented in a range of different NMR experiments. Paradoxically, PSYCHE is one of the trickiest of pure shift NMR techniques to understand but one of the easiest to use. Here we offer some insights into theoretical and practical aspects of the method, and into the effects and importance of the experimental parameters. Some recent improvements that enhance the spectral purity of PSYCHE spectra will be presented, and some experimental frameworks, including examples in 1D and 2D NMR spectroscopy, for the implementation of PSYCHE will be introduced.

Ultraclean pure shift NMR.

"Pure shift" methods can greatly improve the resolution of proton NMR spectra. However, current pure shift spectra show small periodic artefacts that prevent their use for studying dilute mixture components. A new technique, compatible with all current pure shift methods, is presented that suppresses such sidebands to arbitrary order, allowing ultraclean spectra to be obtained.

Ultrahigh-Resolution Diffusion-Ordered Spectroscopy.

Diffusion-ordered spectroscopy (DOSY) is an effective method for the analysis of intact mixtures, but the quality of results is critically limited by resolution in the NMR dimension. A new experiment integrating diffusion weighting into the PSYCHE method for pure shift NMR spectroscopy allows DOSY spectra to be measured with ultrahigh NMR resolution at improved sensitivity.

Very broadband diffusion-ordered NMR spectroscopy: (19)F DOSY.

A new pulse sequence, CHORUS Oneshot, allows measurements of diffusion-ordered spectroscopy (DOSY) spectra over the full chemical shift range of (19)F for the first time. Swept-frequency pulses are used to give very broadband excitation; the sequence is a prototype for a large family of very broadband liquid state NMR methods.

A General Method for Extracting Individual Coupling Constants from Crowded (1)H†NMR Spectra.

Couplings between protons, whether scalar or dipolar, provide a wealth of structural information. Unfortunately, the high number of (1)H-(1)H couplings gives rise to complex multiplets and severe overlap in crowded spectra, greatly complicating their measurement. Many different methods exist for disentangling couplings, but none approaches optimum resolution. Here, we present a general new 2D J-resolved method, PSYCHEDELIC, in which all homonuclear couplings are suppressed in F2, and only the couplings to chosen spins appear, as simple doublets, in F1. This approaches the theoretical limit for resolving (1)H-(1)H couplings, with close to natural linewidths and with only chemical shifts in F2. With the same high sensitivity and spectral purity as the parent PSYCHE pure shift experiment, PSYCHEDELIC offers a robust method for chemists seeking to exploit couplings for structural, conformational, or stereochemical analyses.

Reconstruction of full high-resolution HSQC using signal split in aliased spectra.

Resolution enhancement is a long-sought goal in NMR spectroscopy. In conventional multidimensional NMR experiments, such as the (1) H-(13) C HSQC, the resolution in the indirect dimensions is typically 100 times lower as in 1D spectra because it is limited by the experimental time. Reducing the spectral window can significantly increase the resolution but at the cost of ambiguities in frequencies as a result of spectral aliasing. Fortunately, this information is not completely lost and can be retrieved using methods in which chemical shifts are encoded in the aliased spectra and decoded after processing to reconstruct high-resolution (1) H-(13) C HSQC spectrum with full spectral width and a resolution similar to that of 1D spectra. We applied a new reconstruction method, RHUMBA (reconstruction of high-resolution using multiplet built on aliased spectra), to spectra obtained from the differential evolution for non-ambiguous aliasing-HSQC and the new AMNA (additional modulation for non-ambiguous aliasing)-HSQC experiments. The reconstructed spectra significantly facilitate both manual and automated spectral analyses and structure elucidation based on heteronuclear 2D experiments. The resolution is enhanced by two orders of magnitudes without the usual complications due to spectral aliasing.

Real-time pure shift ¹5N HSQC of proteins: a real improvement in resolution and sensitivity.

Spectral resolution in proton NMR spectroscopy is reduced by the splitting of resonances into multiplets due to the effect of homonuclear scalar couplings. Although these effects are often hidden in protein NMR spectroscopy by low digital resolution and routine apodization, behind the scenes homonuclear scalar couplings increase spectral overcrowding. The possibilities for biomolecular NMR offered by new pure shift NMR methods are illustrated here. Both resolution and sensitivity are improved, without any increase in experiment time. In these experiments, free induction decays are collected in short bursts of data acquisition, with durations short on the timescale of J-evolution, interspersed with suitable refocusing elements. The net effect is real-time (t 2) broadband homodecoupling, suppressing the multiplet structure caused by proton-proton interactions. The key feature of the refocusing elements is that they discriminate between the resonances of active (observed) and passive (coupling partner) spins. This can be achieved either by using band-selective refocusing or by the BIRD element, in both cases accompanied by a nonselective 180° proton pulse. The latter method selects the active spins based on their one-bond heteronuclear J-coupling to (15)N, while the former selects a region of the (1)H spectrum. Several novel pure shift experiments are presented, and the improvements in resolution and sensitivity they provide are evaluated for representative samples: the N-terminal domain of PGK; ubiquitin; and two mutants of the small antifungal protein PAF. These new experiments, delivering improved sensitivity and resolution, have the potential to replace the current standard HSQC experiments.

Flaws in foldamers: conformational uniformity and signal decay in achiral helical peptide oligomers.

Although foldamers, by definition, are extended molecular structures with a well-defined conformation, minor conformers must be populated at least to some extent in solution. We present a quantitative analysis of these minor conformers for a series of helical oligomers built from achiral but helicogenic α-amino acids. By measuring the chain length dependence or chain position dependence of NMR or CD quantities that measure screw-sense preference in a helical oligomer, we quantify values for the decay constant of a conformational signal as it passes through the molecular structure. This conformational signal is a perturbation of the racemic mixture of M and P helices that such oligomers typically adopt by the inclusion of an N or C terminal chiral inducer. We show that decay constants may be very low (<1% signal loss per residue) in non-polar solvents, and we evaluate the increase in decay constant that results in polar solvents, at higher temperatures, and with more conformationally flexible residues such as Gly. Decay constants are independent of whether the signal originates from the N or the C terminus. By interpreting the decay constant in terms of the probability with which conformations containing a screw-sense reversal are populated, we quantify the populations of these alternative minor conformers within the overall ensemble of secondary structures adopted by the foldamer. We deduce helical persistence lengths for Aib polymers that allow us to show that in a non-polar solvent a peptide helix, even in the absence of chiral residues, may continue with the same screw sense for approximately 200 residues.