Enhanced Sensitivity and Resolution in 1 H Solid-State NMR Spectroscopy of Paramagnetic Complexes under Very Fast Magic Angle Spinning Nalinda P. Wickramasinghe, Medhat Shaibat, and Yoshitaka Ishii* Department of Chemistry, UniVersity of Illinois at Chicago, Chicago Illinois 60607 Received December 28, 2004; E-mail: yishii@uic.edu Paramagnetic complexes in solids have attracted increasing interest due to their diverse applications in modern material science, 1,2 bioinorganic chemistry, 3 and pharmacology. 4 Character- izing these paramagnetic complexes is essential to understand their functions and design improved systems. However, the methodolo- gies for characterizing paramagnetic systems have been limited, compared to those for diamagnetic systems, in particular, for noncrystalline solids. Electron paramagnetic resonance (EPR) is a standard method for analyzing paramagnetic systems. However, EPR typically requires isotope labeling to obtain structural informa- tion on ligands through a hyperfine dipolar coupling. Solution NMR, a powerful tool for organic compounds, often exhibits limited resolution and sensitivity for paramagnetic materials because of paramagnetic broadening. 5 Also, solution NMR does not provide unique characteristics in solids such as morphologies, which can alter essential properties of materials and drugs. Solid-state NMR (SSNMR) is a powerful method for structural analysis of noncrystalline solids. Among various nuclei, 13 C SSNMR has been most widely applied for its excellent resolution. However, the limited sensitivity of 13 C SSNMR has required larger amount of samples (0.1-1 mmol), compared with other analysis because of low abundance of 13 C. 1 H SSNMR is an attractive alternative to 13 C SSNMR, particularly for unlabeled systems and samples in limited quantities because of its high sensitivity. 6,7 In 1 H high-resolution SSNMR, multiple-pulse 1 H- 1 H RF dipolar decoupling has been required, together with magic angle spinning (MAS) to suppress line broadening due to strong 1 H- 1 H couplings. 6 On the other hand, for paramagnetic complexes, large paramagnetic shifts have inhibited resolution enhancement by multiple-pulse decoupling. Nayman et al. 8 and later Liu et al. 9 demonstrated that moderate spinning about 10 kHz improves resolution for paramag- netic systems. However, this unique idea is only effective for systems in which 1 H- 1 H flip-flop is suppressed by large 1 H shift dispersion or motions. Therefore, few 1 H high-resolution NMR studies have been performed for paramagnetic systems. Recently, our group demonstrated a new approach to obtain high- resolution 13 C SSNMR of paramagnetic systems using very fast MAS (VFMAS; spinning speed, ν R > 20 kHz). 10 Although MAS over 50 kHz is currently available, 11 we define VFMAS as above because MAS at 20 kHz or more induces crucial changes in the spin dynamics for organic solids by eliminating the majority of 1 H- 1 H and 1 H- 13 C dipolar couplings. Faster spinning (ν R > 30 kHz) does not qualitatively alter this spin dynamics, which forms the foundation of our approach. Although 1 H line narrowing by VFMAS has been shown for diamagnetic systems, 7,12 this has not been discussed for paramagnetic systems. In this study, we demonstrate that 1 H high-resolution SSNMR of paramagnetic systems under VFMAS exhibits excellent resolution and unparal- leled sensitivity, permitting SSNMR micro analysis. Figure 1a-c shows the spinning-speed dependence of 1 H MAS spectra of unlabeled Cu(DL-Ala) 2 ‚H 2 O. It is clear that the sensitivity and resolution are both excellent at ν R ) 24 kHz in (a). VFMAS significantly enhanced resolution and sensitivity by removing broadening due to large anisotropic paramagnetic shifts as well as other anisotropic interactions such as 1 H- 1 H dipolar couplings. 10 Compared with the spectrum in (b) at ν R ) 10 kHz, the sensitivity enhancement in (a) is a factor of 12-18. It is worth pointing out that anisotropic paramagnetic shifts are generally proportional to (S + 1)Sγ I /R IS 3 , 5 where γ I is the gyromagnetic ratio for the nuclear spin I, S is an electron spin number, and R IS is a distance between I and the electron spin S at a paramagnetic center. Hence, a higher γ nucleus is subject to a larger anisotropic shift in Hz units (S ) 1 / 2 for this system). Nevertheless, most of the spinning sidebands were suppressed in (a). It is also important to point out that besides VFMAS, fast electron spin exchange by intermolecular spin couplings in solids enhances the resolution of SSNMR. 8,9 In solution NMR, molecules isolated in solvents often have long electron spin relaxation times, which lead to quenching of NMR signals. 13 The assignments given in (a) are based on 2D 13 C/ 1 H correlation NMR, as will be described elsewhere. The assignments agree well with those based on 2 D NMR of selectively 2 D-labeled samples. 9 Although we did not assign the signal at 20 ppm, a corresponding signal was assigned to a minor CD 3 species in 2 D NMR. 9 Figure 1a exhibiting well-resolved center bands was obtained in a total experimental time of only 18 ms because of short 1 H T 1 values. Figure 1d-f shows spinning-speed dependence of 1 H MAS spectra of Mn(acac) 3 (S ) 5 / 2 ). In (f) at ν R ) 5 kHz, there are no resolved signals, and only one center band is visible in (e) at 10 kHz. In contrast, the resolution and sensitivity are both significantly enhanced by VFMAS at 27.8 kHz in (d). Compared with the spectrum at 10 kHz in (e), sensitivity enhancement by a factor of 17 was observed at 27.8 kHz. Because the 1 H paramagnetic anisotropic shifts reach 1000 ppm, a conventional multiple-pulse Figure 1. Spinning speed dependence of 1 H MAS spectra of (a-c) Cu(DL-Ala)2‚(H2O) and (d-f) Mn(acac)3. The spinning speed is indicated in the figure. The inset in (d) is the expanded center line region. The spectra were obtained at 1 H frequency of 400.2 MHz with 1-pulse excitation and a rotor synchronous echo with 4 scans for each spectrum. The sample amount was 17 and 14 mg for Cu(DL-Ala)2 and Mn(acac)3, respectively. The assignment for Cu(DL-Ala)2 and Mn(acac)3 was obtained from separate 2D 13 C/ 1 H correlation NMR experiments. The total experimental times were only (a-c) 18 ms and (d-f) 12 ms. Other experimental details are available in the Supporting Information. Published on Web 04/05/2005 5796 9 J. AM. CHEM. SOC. 2005, 127, 5796-5797 10.1021/ja042188i CCC: $30.25 © 2005 American Chemical Society