H and C pNMR properties of bis(salicylaldoximato)copper(II) were studied in the solid state using magic-angle-spinning NMR spectroscopy and, for the isolated complex and selected oligomers, using density-functional theory at the PBE0-1/3 //PBE0-D3 level. Large paramagnetic shifts are observed, up to δ( H)=272 ppm and δ( C)=1006 ppm (at 298 K), which are rationalised through spin delocalisation from the metal onto the organic ligand and the resulting contact shifts arising from hyperfine coupling. The observed shift ranges are best reproduced computationally using exchange-correlation functionals with a high fraction of exact exchange (such as PBE0-1/3 ). Through a combination of experimental techniques and first-principles computation, a near-complete assignment of the observed signals is possible. Intermolecular effects on the pNMR shifts, modelled computationally in the dimers and trimers through effective decoupling between the local spins via A-tensor and total spin rescaling in the pNMR expression, are indicated to be small. Addition of electron-donating substituents and benzannelation of the organic ligand is predicted computationally to induce notable changes in the NMR signal pattern, which suggests that pNMR spectroscopy can be a sensitive probe for the spin distribution in paramagnetic phenolic oxime copper complexes.

We present a strategy for predicting the unusual 1 H and 13 C shifts in NMR spectra of paramagnetic bisoximato copper(II) complexes using DFT. We demonstrate good agreement with experimental measurements, although 1 H-13 C correlation spectra show that a combined experimental and theoretical approach remains necessary for full assignment.In recent years, paramagnetic NMR (or "pNMR") has developed greatly, with systems from metalloproteins 1 (dilute, isolated spins) to metal-organic frameworks 2-4 (denser networks of potentially coupled spins) and metal oxides 5 (very dense networks of highly coupled spins) being studied. For dilute spins, the NMR conditions can be selected such that the signal from nuclei near the paramagnetic centre is "invisible" owing to rapid relaxation and only the longer-range throughspace pseudocontact shifts are observed. 1 These are generally on the order of a few ppm and occur over distances such that the unpaired electron can be treated as a point spin, resulting in a simple 1/r 3 relationship with the shift. For dense spin networks such as transition metal oxides, it may be possible to assign the NMR spectra by analysis of bonding pathways (via oxygen). 5 However, in the intermediate regime, including materials such as catalytically-active transition metal complexes and metal-organic frameworks (MOFs), both the through-bond Fermi contact and through-space pseudocontact interactions affect the observed NMR spectrum and assignment can be both nontrivial and counterintuitive. 2,6-9 For example, in the 13 C NMR spectrum of the MOF HKUST-1 (Cu3btc2, btc = benzene-1,3,5-tricarboxylate), 10 the broadest resonance, shifted most by paramagnetic interactions, is not the carboxylate C (separated from Cu 2+ by just two bonds), but rather the adjacent quaternary C (three bonds from Cu). This assignment was confirmed using the relatively costly and timeconsuming approach of specific 13 C labelling in conjunction with 1 H-13 C cross polarisation (CP) NMR, which is generally inefficient for paramagnetic materials. 2 It would, therefore, be desirable to have a more general assignment method that does not rely on the development of bespoke synthetic pathways for efficient isotopic enrichment. Owing to the rapid MAS rates (necessitating the use of small rotors with, consequently, small sample volumes) required for highresolution pNMR spectra, sensitivity is inherently low and it would, therefore, also be advantageous to be able to predict shifts prior to the experimental measurement, particularly as resonances can be several hundred ppm away from their typical diamagnetic range.Periodic density functional theory (DFT) calculations have enjoyed great success in solid-state NMR, allowing the optimisation of experimental structures to an energy minimum and the subsequent calculation of highly accurate NMR parameters [11][12][13] However, pNMR DFT calculations are still in their relative infancy, particularly for periodic solids. The field is more advanced for molecular calculations, which have successfull...

MethodsMale rats were ‘pretreated’ with phosphate-buffered saline (PBS; i.p.) or LPS (1 mg/kg; i.p.) 24 h prior to HS. Mean arterial pressure (MAP) was maintained at 30 ± 2 mmHg for 90 min or until 25% of the shed blood had to be re-injected to sustain MAP. This was followed by resuscitation with the remaining shed blood. Four hours after resuscitation, parameters of organ dysfunction and systemic inflammation were assessed.ResultsHS resulted in renal dysfunction, and liver and muscular injury. At a first glance, LPS preconditioning attenuated organ dysfunction. However, we discovered that HS-rats that had been preconditioned with LPS (a) were not able to sustain a MAP at 30 mmHg for more than 50 min and (b) the volume of blood withdrawn in these animals was significantly less than in the PBS-control group. This effect was associated with an enhanced formation of the nitric oxide (NO) derived from inducible NO synthase (iNOS). Thus, a further control group in which all animals were resuscitated after 50 min of hemorrhage was performed. Then, LPS preconditioning aggravated both circulatory failure and organ dysfunction. Most notably, HS-rats pretreated with LPS exhibited a dramatic increase in NF-κB activation and pro-inflammatory cytokines.ConclusionIn conclusion, LPS preconditioning predisposed animals to an earlier vascular decompensation, which may be mediated by an excess of NO production secondary to induction of iNOS and activation of NF-κB. Moreover, LPS preconditioning increased the formation of pro-inflammatory cytokines, which is likely to have contributed to the observed aggravation of organ injury/dysfunction caused by HS.