Minimizing the t1-noise when using an indirect 1H high-resolution detection of unlabeled samples.

The most utilized through-space correlation 1H-{X} methods with proton indirect detection use two consecutive transfers, 1H â†’ X and then X â†’ 1H, with the evolution time t1 in the middle. When the X isotope is not 100% naturally abundant (NA), only the signal of the protons close to these isotopes is modulated by the 1H-X dipolar interactions. This signal is theoretically disentangled with phase-cycling from the un-modulated one. However, this separation is never perfect and it may lead to t1-noise in case of isotopes with very small NA, such as 13C or even worse 15N. One way to reduce this t1-noise is to minimize, 'purge', during t1 the un-modulated 1H magnetization before trying to suppress it with phase-cycling. We analyze experimentally several sequences following the HORROR condition, which allow purging the 1H transverse magnetization. The comparison is made at three spinning speeds, including very fast ones for 1H resolution: 27.75, 55.5 and 111 kHz. We show (i) that the efficiency of this purging process increases with the spinning speed, and (ii) that the best recoupling sequences are the two simplest ones: XY and S1 = SR212. We then compare the S/N that can be achieved with the two most used 1H-{X} 2D methods, called D-HMQC and CP-CP. The only difference in between these two methods is that the transfers are done with either two π/2-pulses on X channel (D-HMQC), or two Cross-Polarization (CP) transfers (CP-CP). The first method, D-HMQC, is very robust and should be preferred when indirectly detecting nuclei with high NA. The second method, CP-CP, (i) requires experimental precautions to limit the t1-noise, and (ii) is difficult to use with quadrupolar nuclei because the two CP transfers are then not efficient nor robust. However, CP-CP is presently the best method to indirectly detect isotopes with small NA, such as 13C and 15N.

Accurate NMR determination of C-H or N-H distances for unlabeled molecules.

Cross-Polarization with Variable Contact-time (CP-VC) is very efficient at ultra-fast MAS (νR ≥ 60 kHz) to measure accurately the dipolar interactions corresponding to C-H or N-H short distances, which are very useful for resonance assignment and for analysis of dynamics. Here, we demonstrate the CP-VC experiment with (1)H detection. In the case of C-H distances, we compare the CP-VC signals with direct ((13)C) and indirect ((1)H) detection and find that the latter allows a S/N gain of ca. 2.5, which means a gain of ca. 6 in experimental time. The main powerful characteristics of CP-VC methods are related to the ultra-fast spinning speed and to the fact that most of the time only the value of the dipolar peak separation has to be used to obtain the information. As a result, CP-VC methods are: (i) easy to set up and to use, and robust with respect to (ii) rf-inhomogeneity thus allowing the use of full rotor samples, (iii) rf mismatch, and (iv) offsets and chemical shift anisotropies. It must be noted that the CP-VC 2D method with indirect (1)H detection requires the proton resolution and is thus mainly applicable to small or perdeuterated molecules. We also show that an analysis of the dynamics can even be performed, with a reasonable experimental time, on unlabeled samples with (13)C or even (15)N natural abundance.

Theoretical study of CP-VC: a simple, robust and accurate MAS NMR method for analysis of dipolar C-H interactions under rotation speeds faster than ca. 60 kHz.

We show that Cross-Polarization with Variable Contact-time (CP-VC) allows an accurate determination of C-H dipolar interactions, which permits an easy detailed analysis of bond lengths and local dynamics, e.g. in biomolecules. The method presents a large dipolar scaling factor of 1/√2, leading to a better determination of dipolar interactions, especially for long C-H distances, and it allows the observation of very small local details such as those related either to CH(2) three spin systems, or even to hydrogen bonds. CP-VC is very simple to set up and very robust with respect to most experimental parameters, such as: rf-offsets, chemical-shift anisotropies, imperfect Hartmann-Hahn setting, and rf-inhomogeneity. The only required condition is the use of a sufficiently fast MAS spinning speed of at least ca. 60 kHz.

Improving the resolution in proton-detected through-space heteronuclear multiple quantum correlation NMR spectroscopy.

Connectivities and proximities between protons and low-gamma nuclei can be probed in solid-state NMR spectroscopy using two-dimensional (2D) proton-detected heteronuclear correlation, through Heteronuclear Multiple Quantum Correlation (HMQC) pulse sequence. The indirect detection via protons dramatically enhances the sensitivity. However, the spectra are often broadened along the indirect F1 dimension by the decay of heteronuclear multiple-quantum coherences under the strong (1)H-(1)H dipolar couplings. This work presents a systematic comparison of the performances of various decoupling schemes during the indirect t1 evolution period of dipolar-mediated HMQC (D-HMQC) experiment. We demonstrate that (1)H-(1)H dipolar decoupling sequences during t1, such as symmetry-based schemes, phase-modulated Lee-Goldburg (PMLG) and Decoupling Using Mind-Boggling Optimization (DUMBO), provide better resolution than continuous wave (1)H irradiation. We also report that high resolution requires the preservation of (1)H isotropic chemical shifts during the decoupling sequences. When observing indirectly broad spectra presenting numerous spinning sidebands, the D-HMQC sequence must be fully rotor-synchronized owing to the rotor-synchronized indirect sampling and dipolar recoupling sequence employed. In this case, we propose a solution to reduce artefact sidebands caused by the modulation of window delays before and after the decoupling application during the t1 period. Moreover, we show that (1)H-(1)H dipolar decoupling sequence using Smooth Amplitude Modulation (SAM) minimizes the t1-noise. The performances of the various decoupling schemes are assessed via numerical simulations and compared to 2D (1)H-{(13)C} D-HMQC experiments on [U-(13)C]-L-histidine⋅HCl⋅H2O at various magnetic fields and Magic Angle spinning (MAS) frequencies. Great resolution and sensitivity enhancements resulting from decoupling during t1 period enable the detection of heteronuclear correlation between aliphatic protons and ammonium (14)N sites in L-histidine⋅HCl⋅H2O.

Observation of proximities between spin-1/2 and quadrupolar nuclei: which heteronuclear dipolar recoupling method is preferable?

We have recently shown that the dipolar-mediated heteronuclear multiple-quantum coherence (D-HMQC) method allows observing through-space proximities between spin-1/2 ((1)H, (13)C, (31)P...) and quadrupolar ((23)Na, (27)Al...) nuclei. However, the D-HMQC effectiveness depends on the choice of the heteronuclear dipolar recoupling sequence. Here, we compare the efficiency and the robustness of four rotor-synchronized sequences: the symmetry-based ones, R4(1)(2)R4(1)(-2) and its super-cycled version, SR4(1)(2), and two schemes based on simultaneous amplitude and frequency modulations, denoted SFAM-1 and SFAM-2. For the SFAM methods, we point out efficient recoupling conditions that facilitate their experimental optimization and we introduce analytical expressions for the buildup of D-HMQC signal in the case of an isolated spin pair. We show that the main differences between these four sequences lie in the number of adjustable parameters and in their robustness with respect to chemical shift and homonuclear dipolar interactions. The relative performances of these four recoupling sequences are analyzed using average Hamiltonian theory, numerical simulations, and (27)Al-{(31)P} D-HMQC experiments on crystalline aluminophosphate.

Structural characterisation of phosphate materials: new insights into the spatial proximities between phosphorus and quadrupolar nuclei using the D-HMQC MAS NMR technique.

We show in this article how the spatial proximity between phosphorus and quadrupolar nuclei can be efficiently and easily investigated with the D-HMQC (Dipolar Hetero-nuclear Multiple-Quantum Coherences) NMR technique. Compared to the commonly used CP-HETCOR (Cross-Polarisation HETero-nuclear CORrelation) sequence, the D-HMQC pulse scheme exhibits a higher sensitivity and a better robustness with respect to spinning frequency, electronic shielding and quadrupole interaction, and thus does not require time-consuming and complicated optimisation procedures. The advantages of the D-HMQC are demonstrated in this article through the acquisition of (31)P/S through-space two-dimensional correlation NMR spectra providing unreported structural information on (i) a sodium alumino-silicate glass doped with only 3% of P(2)O(5), (ii) a potassium boro-phosphate glass containing BO(3) and BO(4) groups and (iii) a crystalline zirconium vanado-phosphate. All these systems, representative of the most important mixed phosphate network materials, cannot be correctly investigated with the conventional CP-HETCOR NMR technique.

Double-quantum homonuclear NMR correlation spectroscopy of quadrupolar nuclei subjected to magic-angle spinning and high magnetic field.

We present a new application of the R2(2)(1) symmetry-based dipolar recoupling scheme, for exciting directly double-quantum (2Q) coherences between the central transition of homonuclear half-integer quadrupolar nuclei. With respect to previously published 2Q-recoupling methods (M. Eden, D. Zhou, J. Yu, Chem. Phys. Lett. 431 (2006) 397), the R2(2)(1) sequence is used without pi/2 bracketing pulses and with an original super-cycling. This leads to an improved efficiency (a factor of two for spin-5/2) and to a much higher robustness to radio-frequency field inhomogeneity and resonance offset. The 2Q-coherence excitation performances are demonstrated experimentally by (27)Al NMR experiments on the aluminophosphates berlinite, VPI5, AlPO(4)-14, and AlPO(4)-CJ3. The two-dimensional 2Q-1Q correlation experiments incorporating these recoupling sequences allow the observation of 2Q cross-peaks between central transitions, even at high magnetic field where the difference in offset between octahedral and tetrahedral (27)Al sites exceeds 10 kHz.

Double-quantum NMR spectroscopy of 31P species submitted to very large CSAs.

We introduce an original pulse sequence, BR2(2)(1)(taupitau), which is a block super-cycled R2(2)(1) sequence employing as basic element a pi pulse sandwiched by 'window' intervals. This homonuclear dipolar recoupling method allows the efficient excitation of double-quantum coherences between spin-1/2 nuclei submitted to very large chemical shift anisotropy. We demonstrate that this technique can be employed in double-quantum<-->single-quantum (31)P homonuclear correlation experiment at high magnetic field (B(0)>or=14 T) and high MAS frequencies (nu(R)>or=30 kHz). The performances of BR2(2)(1)(taupitau) are compared to those of the double-quantum recoupling methods, such as BABA and bracketed fp-RFDR, which were already employed at fast MAS rates. The BR2(2)(1)(taupitau) sequence displays a higher robustness to CSA and offset than the other existing techniques.

Robust and efficient spin-locked symmetry-based double-quantum homonuclear dipolar recoupling for probing (1)H-(1)H proximity in the solid-state.

We report a novel symmetry-based method, using inversion elements bracketed by spin locks, for exciting double-quantum (DQ) coherences between spin-1/2 nuclei, such as protons. Compared to previous DQ-recoupling techniques, this new pulse sequence requires moderate rf field, even at ultra-fast MAS speeds. Furthermore, it is easy to implement and it displays higher robustness to both chemical shift anisotropy and to spreads in resonance frequencies. These advances greatly facilitate the observation of (1)H-(1)H proximities at high fields and high MAS frequencies.

Correlation NMR spectroscopy involving quadrupolar nuclei.

We review the recent developments proposed for integer or half-integer quadrupolar nuclei, focussing on the methods to observe them under high-resolution and to analyze their through-space and through-bond connectivities.

Heteronuclear dipolar decoupling effects on multiple-quantum and satellite-transition magic-angle spinning NMR spectra.

We here report on the influence of heteronuclear dipolar decoupling on the (27)Al 3QMAS, 5QMAS, and the double-quantum filter-satellite-transition magic-angle spinning (DQF-STMAS) spectra of a strongly dipolar-coupled system, gibbsite. The requirements for heteronuclear dipolar decoupling increase with the order of coherence evolving in the indirect dimension of a two-dimensional (2D) experiment. The isotropic line width of the high-resolution 2D spectra, in samples like gibbsite, is composed of four parts: the distribution of isotropic shifts (delta(ISO), delta(QIS)), the homogeneous broadening related to the proton-proton flip-flop terms, the (27)Al-(27)Al homonulcear dipolar couplings, and the (1)H-(27)Al heteronuclear dipolar couplings. It is shown that, even in the case of gibbsite, where a strong proton-proton bath exists, the main resolution limiting factor in these experiments resides in the (1)H-(27)Al dipolar interaction.

Through-space MP-CPMAS experiments between spin-1/2 and half-integer quadrupolar nuclei in solid-state NMR.

We present a new CPMAS method that allows the acquisition of through-space 2D HETCOR spectra between spin-1/2 nuclei and half-integer quadrupolar nuclei in the solid state. It uses rotor-synchronized selective pulses on the quadrupolar nucleus and continuous-wave RF irradiation on the spin-1/2 nucleus to create hetero-nuclear dipolar coherences. The method is more robust, more efficient, and easier to set up than the standard CPMAS transfer.

Comparison of several hetero-nuclear dipolar recoupling NMR methods to be used in MAS HMQC/HSQC.

We compare several hetero-nuclear dipolar recoupling sequences available for HMQC or HSQC experiments applied to spin-1/2 and quadrupolar nuclei. These sequences, which are applied to a single channel, are based either on the rotary resonance recoupling (R3) irradiation, or on two continuous rotor-synchronized modulations (SFAM1 and SFAM2), or on four symmetry-based sequences (R2(1)1,SR4(1)2,R12(3)5,R20(5)9), or on the REDOR scheme. We analyze systems exhibiting purely hetero-nuclear dipolar interactions as well as systems where homo-nuclear dipolar interactions need to be canceled. A special attention is given to the behavior of these sequences at very fast MAS. It is shown that R3 methods behave poorly due to the narrowness of their rf-matching curves, and that the best methods are SR4(1)2 and SFAM (SFAM1 or SFAM2 if homo-nuclear interactions are not negligible). REDOR can also recouple efficiently hetero-nuclear dipolar interactions, provided the sequence is sent on the non-observed channel and homo-nuclear dipolar interactions are negligible. We anticipate that at ultra-fast spinning speed, SFAM1 and SFAM2 will be the most efficient methods.

Measurement of through-space connectivities between spin-1/2 and quadrupolar nuclei in solid-state NMR: the TEDOR-MQMAS method.

We present the transferred echo double-resonance multiple-quantum MAS (TEDOR-MQMAS) method that allows to analyze under high resolution the through-bond connectivities between spin-1/2 and quadrupolar nuclei. This method avoids some of the limitations related to the spin-lock of half-integer quadrupolar nuclei under MAS. However, the losses observed during the TEDOR transfer are related to the T'(2) constants, and they may thus be more important than those observed during the CP-MAS transfer, which are related to T(1rho) > T'(2).

Through-space R3-HETCOR experiments between spin-1/2 and half-integer quadrupolar nuclei in solid-state NMR.

We present several new methods that allow to obtain through-space 2D HETCOR spectra between spin-1/2 and half-integer quadrupolar nuclei in the solid state. These methods use the rotary-resonance concept to create hetero-nuclear coherences through the dipolar interaction instead of scalar coupling into the HMQC and refocused INEPT experiments for spin n/2 (n>1). In opposite to those based on the cross-polarization transfer to quadrupolar nuclei, the methods are very robust and easy to set-up.

Resolution enhancement using a new multiple-pulse decoupling sequence for quadrupolar nuclei.

A new decoupling composite pulse sequence is proposed to remove the broadening on spin S=1/2 magic-angle spinning (MAS) spectra arising from the scalar coupling with a quadrupolar nucleus I. It is illustrated on the (31)P spectrum of an aluminophosphate, AlPO(4)-14, which is broadened by the presence of (27)Al/(31)P scalar couplings. The multiple-pulse (MP) sequence has the advantage over the continuous wave (CW) irradiation to efficiently annul the scalar dephasing without reintroducing the dipolar interaction. The MP decoupling sequence is first described in a rotor-synchronised version (RS-MP) where one parameter only needs to be adjusted. It clearly avoids the dipolar recoupling in order to achieve a better resolution than using the CW sequence. In a second improved version, the MP sequence is experimentally studied in the vicinity of the perfect rotor-synchronised conditions. The linewidth at half maximum (FWHM) of 65 Hz using (27)Al CW decoupling decreases to 48 Hz with RS-MP decoupling and to 30 Hz with rotor-asynchronised MP (RA-MP) decoupling. The main phenomena are explained using both experimental results and numerical simulations.

HMQC and refocused-INEPT experiments involving half-integer quadrupolar nuclei in solids.

Hetero-nuclear coherence transfers in HMQC and refocused-INEPT experiments involving half-integer quadrupolar nuclei in solids are analyzed. 1D and 2D schemes are considered under MAS for the general case of multi-spin systems SI(n) (n4), where S is an observed nucleus. These results are also discussed in the context of high-resolution schemes featuring MQMAS or STMAS. The theoretical predictions are verified experimentally in a series of 1D and 2D experiments performed at 9.4 and 18.8T.

Homogeneous broadenings in 2D solid-state NMR of half-integer quadrupolar nuclei.

The question of the homogeneous broadening that occurs in 2D solid-state NMR experiments is examined. This homogeneous broadening is mathematically introduced in a simple way, versus the irreversible decay rates related to the coherences that are involved during t1 and t2. We give the pulse sequences and coherence transfer pathways that are used to measure these decay rates. On AlPO4 berlinite, we have measured the 27Al echo-type relaxation times of the central and satellite transitions on 1Q levels, so that of coherences that are situated on 2Q, 3Q, and 5Q levels. We compare the broadenings that can be deduced from these relaxation times to those directly observed on the isotropic projection of berlinite with multiple-quantum magic-angle spinning (MAS), or satellite-transition MAS. We show that the choice of the high-resolution method, should be done according to the spin value and the corresponding homogeneous broadening.