Condensed Matter Systems Exposed to Radiation: Multiscale Theory, Simulations, and Experiment.

This roadmap reviews the new, highly interdisciplinary research field studying the behavior of condensed matter systems exposed to radiation. The Review highlights several recent advances in the field and provides a roadmap for the development of the field over the next decade. Condensed matter systems exposed to radiation can be inorganic, organic, or biological, finite or infinite, composed of different molecular species or materials, exist in different phases, and operate under different thermodynamic conditions. Many of the key phenomena related to the behavior of irradiated systems are very similar and can be understood based on the same fundamental theoretical principles and computational approaches. The multiscale nature of such phenomena requires the quantitative description of the radiation-induced effects occurring at different spatial and temporal scales, ranging from the atomic to the macroscopic, and the interlinks between such descriptions. The multiscale nature of the effects and the similarity of their manifestation in systems of different origins necessarily bring together different disciplines, such as physics, chemistry, biology, materials science, nanoscience, and biomedical research, demonstrating the numerous interlinks and commonalities between them. This research field is highly relevant to many novel and emerging technologies and medical applications.

Shaping the Future of Fuel: Monolithic Metal-Organic Frameworks for High-Density Gas Storage.

The environmental benefits of cleaner, gaseous fuels such as natural gas and hydrogen are widely reported. Yet, practical usage of these fuels is inhibited by current gas storage technology. Here, we discuss the wide-ranging potential of gas-fuels to revolutionize the energy sector and introduce the limitations of current storage technology that prevent this transition from taking place. The practical capabilities of adsorptive gas storage using porous, crystalline metal-organic frameworks (MOFs) are examined with regard to recent benchmark results and ultimate storage targets in this field. In particular, the industrial limitations of typically powdered MOFs are discussed while recent breakthroughs in MOF processing are highlighted. We offer our perspective on the future of practical, rather than purely academic, MOF developments in the increasingly critical field of environmental fuel storage.

Reactions of Trimethylaluminium: Modelling the Chemical Degradation of Synthetic Lubricants.

In investigating and seeking to mimic the reactivity of trimethylaluminium (TMA) with synthetic, ester-based lubricating oils, the reaction of methyl propionate 1 was explored with 1, 2 and 3 equivalents of the organoaluminium reagent. Spectroscopic analysis points to the formation of the adduct 1(TMA) accompanied only by the low level 1:1 production of Me2 AlOCEtMe2 2 and Me2 AlOMe 3 when an equimolar amount of TMA is applied. The deployment of excess TMA favours reaction to give 2 and 3 over 1(TMA) adduct formation and spectroscopy reveals that in hydrocarbon solution substitution product 2 traps unreacted TMA to yield 2(TMA). The 1 H NMR spectroscopic observation of two Al-Me signals not attributable to free TMA and in the ratio 1:4 suggests the formation of a previously only postulated, symmetrical metallacycle in Me4 Al2 (µ2 -Me)(µ2 -OCEtMe2 ). In the presence of 3, 2(TMA) undergoes thermally induced exchange to yield Me4 Al2 (µ2 -OMe)(µ2 -OCEtMe2 ) 4 and TMA. The reaction of methyl phenylacetate 5 with TMA allows isolation of the crystalline product Me2 AlOCBnMe2 (TMA) 6(TMA), which allows the first observation of the Me4 Al2 (µ2 -Me)(µ2 -OR) motif in the solid state. Distances of 2.133(3) Š(Al-Mebridging ) and 1.951 Š(mean Al-Meterminal ) are recorded. The abstraction of TMA from 6(TMA) by the introduction of Et2 O has yielded 6, which exists as a dimer.

Multicomponent signal unmixing from nanoheterostructures: overcoming the traditional challenges of nanoscale X-ray analysis via machine learning.

The chemical composition of core-shell nanoparticle clusters have been determined through principal component analysis (PCA) and independent component analysis (ICA) of an energy-dispersive X-ray (EDX) spectrum image (SI) acquired in a scanning transmission electron microscope (STEM). The method blindly decomposes the SI into three components, which are found to accurately represent the isolated and unmixed X-ray signals originating from the supporting carbon film, the shell, and the bimetallic core. The composition of the latter is verified by and is in excellent agreement with the separate quantification of bare bimetallic seed nanoparticles.

Structural effects in lithiocuprate chemistry: the elucidation of reactive pentametallic complexes.

TMPLi (TMP=2,2,6,6-tetramethylpiperidide) reacts with Cu(I) salts in the presence of Et2O to give the dimers [{(TMP)2Cu(X)Li2 (OEt2)}2] (X=CN, halide). In contrast, the use of DMPLi (DMP=cis-2,6-dimethylpiperidide) gives an unprecedented structural motif; [{(DMP)2CuLi(OEt2)}2LiX] (X=halide). This formulation suggests a hitherto unexplored route to the in situ formation of Gilman-type bases that are of proven reactivity in directed ortho cupration.

Water sorption studies with mesoporous multivariate monoliths based on UiO-66.

Hierarchical linker thermolysis has been used to enhance the porosity of monolithic UiO-66-based metal-organic frameworks (MOFs) containing 30 wt% 2-aminoterephthalic acid (BDC-NH2) linker. In this multivariate (i.e. mixed-linker) MOF, the thermolabile BDC-NH2 linker decomposed at ∼350 °C, inducing mesopore formation. The nitrogen sorption of these monolithic MOFs was probed, and an increase in gas uptake of more than 200 cm3 g-1 was observed after activation by heating, together with an increase in pore volume and mean pore width, indicating the creation of mesopores. Water sorption studies were conducted on these monoliths to explore their performance in that context. Before heating, monoUiO-66-NH2-30%-B showed maximum water vapour uptake of 61.0 wt%, which exceeded that reported for either parent monolith, while the highly mesoporous monolith (monoUiO-66-NH2-30%-A) had a lower maximum water vapour uptake of 36.2 wt%. This work extends the idea of hierarchical linker thermolysis, which has been applied to powder MOFs, to monolithic MOFs for the first time and supports the theory that it can enhance pore sizes in these materials. It also demonstrates the importance of hydrophilic functional groups (in this case, NH2) for improving water uptake in materials.

Enhancing Drug Delivery Efficacy Through Bilayer Coating of Zirconium-Based Metal-Organic Frameworks: Sustained Release and Improved Chemical Stability and Cellular Uptake for Cancer Therapy.

The development of nanoparticle (NP)-based drug carriers has presented an exciting opportunity to address challenges in oncology. Among the 100,000 available possibilities, zirconium-based metal-organic frameworks (MOFs) have emerged as promising candidates in biomedical applications. Zr-MOFs can be easily synthesized as small-size NPs compatible with intravenous injection, whereas the ease of decorating their external surfaces with functional groups allows for targeted treatment. Despite these benefits, Zr-MOFs suffer degradation and aggregation in real, in vivo conditions, whereas the loaded drugs will suffer the burst effect-i.e., the fast release of drugs in less than 48 h. To tackle these issues, we developed a simple but effective bilayer coating strategy in a generic, two-step process. In this work, bilayer-coated MOF NU-901 remained well dispersed in biologically relevant fluids such as buffers and cell growth media. Additionally, the coating enhances the long-term stability of drug-loaded MOFs in water by simultaneously preventing sustained leakage of the drug and aggregation of the MOF particles. We evaluated our materials for the encapsulation and transport of pemetrexed, the standard-of-care chemotherapy in mesothelioma. The bilayer coating allowed for a slowed release of pemetrexed over 7 days, superior to the typical 48 h release found in bare MOFs. This slow release and the related performance were studied in vitro using both A549 lung cancer and 3T mesothelioma cells. Using high-resolution microscopy, we found the successful uptake of bilayer-coated MOFs by the cells with an accumulation in the lysosomes. The pemetrex-loaded NU-901 was indeed cytotoxic to 3T and A549 cancer cells. Finally, we demonstrated the general approach by extending the coating strategy using two additional lipids and four surfactants. This research highlights how a simple yet effective bilayer coating provides new insights into the design of promising MOF-based drug delivery systems.

On the role of abnormal DL(CO) in ex-smokers without airflow limitation: symptoms, exercise capacity and hyperpolarised helium-3 MRI.

BACKGROUND: The functional effects of abnormal diffusing capacity for carbon monoxide (DLCO) in ex-smokers without chronic obstructive pulmonary disease (COPD) are not well understood. OBJECTIVE: We aimed to evaluate and compare well established clinical, physiological and emerging imaging measurements in ex-smokers with normal spirometry and abnormal DLCO with a group of ex-smokers with normal spirometry and DLCO and ex-smokers with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I COPD. METHODS: We enrolled 38 ex-smokers and 15 subjects with stage I COPD who underwent spirometry, plethysmography, St George's Respiratory Questionnaire (SGRQ), 6 min Walk Test (6MWT), x-ray CT and hyperpolarised helium-3 ((3)He) MRI. The 6MWT distance (6MWD), SGRQ scores, (3)He MRI apparent diffusion coefficients (ADC) and CT attenuation values below -950 HU (RA950) were evaluated. RESULTS: Of 38 ex-smokers without COPD, 19 subjects had abnormal DLCO with significantly worse ADC (p=0.01), 6MWD (p=0.008) and SGRQ (p=0.01) but not RA950 (p=0.53) compared with 19 ex-smokers with normal DLCO. Stage I COPD subjects showed significantly worse ADC (p=0.02), RA950 (p=0.0008) and 6MWD (p=0.005), but not SGRQ (p=0.59) compared with subjects with abnormal DLCO. There was a significant correlation for (3)He ADC with SGRQ (r=0.34, p=0.02) and 6MWD (r=-0.51, p=0.0002). CONCLUSIONS: In ex-smokers with normal spirometry and CT but abnormal DLCO, there were significantly worse symptoms, 6MWD and (3)He ADC compared with ex-smokers with normal DLCO, providing evidence of the impact of mild or early stage emphysema and a better understanding of abnormal DLCO and hyperpolarised (3)He MRI in ex-smokers without COPD.

Hyperpolarized (3) He and (129) Xe MRI: differences in asthma before bronchodilation.

PURPOSE: To compare hyperpolarized helium-3 ((3) He) and xenon-129 ((129) Xe) MRI in asthmatics before and after salbutamol inhalation. MATERIALS AND METHODS: Seven asthmatics provided written informed consent and underwent spirometry, plethysmography, and MRI before and after salbutamol inhalation. (3) He and (129) Xe ventilation defect percent (VDP) and ventilation coefficient of variation (COV) were measured. To characterize the airways spatially related to ventilation defects, wall area percent (WA%) and lumen area (LA) were evaluated for two subjects who had thoracic x-ray computed tomography (CT) acquired 1 year before MRI. RESULTS: Before salbutamol inhalation, (129) Xe VDP (8 ± 5%) was significantly greater than (3) He VDP (6 ± 5%, P = 0.003). Post-salbutamol, there was a significant improvement in both (129) Xe (5 ± 4%, P < 0.0001) and (3) He (4 ± 3%, P = 0.001) VDP, and the improvement in (129) Xe VDP was significantly greater (P = 0.008). (129) Xe MRI COV (Pre: 0.309 ± 0.028, Post: 0.296 ± 0.036) was significantly greater than (3) He MRI COV (Pre: 0.282 ± 0.018, Post: 0.269 ± 0.024), pre- (P < 0.0001) and post-salbutamol (P < 0.0001) and the decrease in COV post-salbutamol was significant ((129) Xe, P = 0.002; (3) He, P < 0.0001). For a single asthmatic, a sub-segmental (129) Xe MRI ventilation defect that was visible only before salbutamol inhalation but not visible using (3) He MRI was spatially related to a remodeled fourth generation sub-segmental airway (WA% = 78%, LA = 2.9 mm(2) ). CONCLUSION: In asthma, hyperpolarized (129) Xe MRI may help reveal ventilation abnormalities before bronchodilation that are not observed using hyperpolarized (3) He MRI.

Manipulating morphology and composition in colloidal heterometallic nanopods and nanodendrites.

Branched Pt nanoparticles represent an exciting class of nanomaterials with high surface areas suitable for applications in electrocatalysis. Introducing a second metal can enhance performance and reduce cost. External factors such as capping agents and temperature have been used to offer insights into nanopod formation and to encourage their kinetic evolution. More recently, nanodendrites have been reported, though synthesis has generally been empirical; making controlled variation of morphology while maintaining bimetallic composition an elusive target. We report the combination of Pt with Fe under a range of conditions, yielding individually bimetallic nanoparticles whose construction sheds new light on nanopod and/or nanodendrite formation. Fine control of metal precursor reduction through modulating capping agents, reagents, and temperature initially directs nanopod synthesis. Morphology control is retained while composition is then varied from Pt-rich to Pt-poor. Additionally, conditions are identified that promote the collision-based branching of nanopod arms. This allows synthesis to be redirected for the selective growth of compositionally controlled nanodendrites in predictable fashion.

Assessment of oil-interceptor performance for solid removal in highway runoff.

Oil interceptors are traditional SuDS devices used in highway runoff treatment to remove both floatable impurities (leaves, oil) and total suspended solids (TSS). This paper presents the results of an examination of the performance of an oil interceptor based on particle size distribution (PSD) and TSS during three rainfall events. The interceptor is situated on one of the busiest motorways in the UK (where peak traffic flow is 30,000 vehicles per hour). Although the overall data collected for this study provided evidence that the interceptor removed, in most cases, 70% of TSS, the data for particle size distribution (PSD) showed that the interceptor did not always cope with particle separation for particles of less than 25 µm diameter.

Hyperpolarized 3He and 129Xe MR imaging in healthy volunteers and patients with chronic obstructive pulmonary disease.

PURPOSE: To quantitatively compare hyperpolarized helium 3 (3He) and xenon 129 (129Xe) magnetic resonance (MR) images obtained within 5 minutes in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD) and to evaluate the correlations between 3He and 129Xe MR imaging measurements and those from spirometry and plethysmography. MATERIALS AND METHODS: This study was approved by an ethics board and compliant with HIPAA. Written informed consent was obtained from all subjects. Eight healthy volunteers and 10 patients with COPD underwent MR imaging, spirometry, and plethysmography. Ventilation defect percentages (VDPs) at 3He and 129Xe imaging were obtained by using semiautomated segmentation. Apparent diffusion coefficients (ADCs) were calculated from 3He (b=1.6 sec/cm2) and 129Xe (b=12 sec/cm2) diffusion-weighted images. VDPs at hyperpolarized 3He and 129Xe imaging were compared with a two-tailed Wilcoxon signed rank test and analysis of variance; Pearson correlation coefficients were used to evaluate the relationships among measurements. RESULTS: 129Xe VDP was significantly greater than 3He VDP for patients with COPD (P<.0001) but not for healthy volunteers (P=.35), although 3He and 129Xe VDPs showed a significant correlation for all subjects (r=0.91, P<.0001). The forced expiratory volume in 1 second (FEV1) showed a similar and significant correlation with 3He VDP (r=-0.84, P<.0001) and 129Xe VDP (r=-0.89, P<.0001), although the correlation between the FEV1/forced vital capacity (FVC) ratio and 129Xe VDP (r=-0.95, P<.0001) was significantly greater (P=.01) than that for FEV1/FVC and 3He VDP (r=-0.84, P<.0001). A significant correlation was also observed for 3He and 129Xe ADC (r=0.97, P<.0001); 129Xe ADC was significantly correlated with diffusing capacity of lung for carbon monoxide (r=-0.79, P=.03) and computed tomographic emphysema measurements (areas with attenuation values in the 15th percentile: r=-0.91, P=.0003; relative areas with attenuation values of less than -950 HU: r=0.87, P=.001). CONCLUSION: In patients with COPD, the VDP obtained with hyperpolarized 29Xe MR imaging was significantly greater than that with 3He MR imaging, suggesting incomplete or delayed filling of lung regions that may be related to the different properties of 129Xe gas and physiologic and/or anatomic abnormalities in COPD.

Lithiated tertiary carbanions display variable coordination modes: evidence from DFT and NMR studies.

Density functional calculations reveal that, whereas the reaction of 2-propyl-N,N-diisopropylbenzamide (6) with tBuLi in the presence of potentially tridentate donor ligands may result in lateral deprotonation of 6, the behavior of the Lewis base is non-trivial. The ability of N and O donor centers in the co-solvent to resist Li(+) coordination is found to be synonymous with interaction of lithium with the formally deprotonated carbanion center. Low-energy structures have been identified whose predicted (1)H and (13)C NMR spectroscopic shifts are in excellent agreement with experiment. Reaction of 2-isopropyl-N,N-diisopropylbenzamide (5) with tBuLi in the presence of bidentate Lewis base N,N,N',N'-tetramethylethylenediamine (TMEDA) yields material that is suggested by NMR spectroscopy to be laterally deprotonated and to have the formulation 5-Li(l)·TMEDA. In spite of the tertiary aliphatic group at the 2-position in 5, X-ray crystallography reveals that the crystalline material isolated from the treatment of 5/(-)-sparteine with tBuLi is a lateral lithiate in which amide coordination and solvation by bidentate Lewis base results in the Li(+) ion interacting with the deprotonated α-C of the 2-iPr group (2.483(8) Å). The tertiary carbanion center remains essentially flat and the adjacent aromatic system is highly distorted. The use of a chiral co-solvent results in two diastereomeric conformers, and their direct observation in solution suggests that interconversion is slow on the NMR timescale.

New Cu-based catalysts supported on TiO2 films for Ullmann S(N)Ar-type C-O coupling reactions.

New routes for the preparation of highly active TiO(2)-supported Cu and CuZn catalysts have been developed for C-O coupling reactions. Slurries of a titania precursor were dip-coated onto glass beads to obtain either structured mesoporous or non-porous titania thin films. The Cu and CuZn nanoparticles, synthesized using a reduction by solvent method, were deposited onto calcined films to obtain a Cu loading of 2 wt%. The catalysts were characterized by inductively coupled plasma (ICP) spectroscopy, temperature-programmed oxidation/reduction (TPO/TPR) techniques, (63)Cu nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction (XRD), scanning and transmission electron microscopy (S/TEM-EDX) and X-ray photo-electron spectroscopy (XPS). The activity and stability of the catalysts obtained have been studied in the C-O Ullmann coupling of 4-chloropyridine and potassium phenolate. The titania-supported nanoparticles retained catalyst activity for up to 12 h. However, catalyst deactivation was observed for longer operation times due to oxidation of the Cu nanoparticles. The oxidation rate could be significantly reduced over the CuZn/TiO(2) catalytic films due to the presence of Zn. The 4-phenoxypyridine yield was 64% on the Cu/nonporous TiO(2) at 120 °C. The highest product yield of 84% was obtained on the Cu/mesoporous TiO(2) at 140 °C, corresponding to an initial reaction rate of 104 mmol g(cat) (-1) s(-1). The activation energy on the Cu/mesoporous TiO(2) catalyst was found to be (144±5) kJ mol(-1), which is close to the value obtained for the reaction over unsupported CuZn nanoparticles (123±3 kJ mol(-1)) and almost twice the value observed over the catalysts deposited onto the non-porous TiO(2) support (75±2 kJ mol(-1)).

Performance linked to residence time distribution by a novel wool-based bioreactor for tertiary sewage treatment.

Laboratory-scale experiments were carried out using up-flow 7 L Submerged Aerated Filter reactors packed with wool fibre or commercial plastic pall rings, Kaldnes, (70% by volume) support media for the tertiary treatment of sewage. The performance of the wool bioreactor was more consistent than that with Kaldnes medium, for both TOC removal (93%) and SS removal (90%). Both plastic and wool-packed bioreactors achieved complete nitrification at the load of about 0.4 kgCOD/m(3)/day. The sludge yield of the wool bioreactor was almost half that of the bioreactor with Kaldnes suggesting that wool could retain residual organics and particulates. The wool however was degraded and it was concluded that wool would have to be considered as additional sacrificial adsorption capacity rather than an alternative medium. The performance was linked to the residence time distribution studies and these changes in the wool structure. Biomass growth increased the retention of the tracer in the wool reactor by, it was suggested, exposing a greater surface area. Results from the plastic media on the other hand showed increased mixing possibly by increasing the mobility of the plastic. Aeration increased the mixing in both reactors, and patterns were in all cases predominantly well-mixed.

On the control of secondary carbanion structure utilising ligand effects during directed metallation.

N,N-Diisopropyl-2-propylbenzamide 6-H undergoes lateral deprotonation by t-BuLi in the presence of the Lewis base PMDTA (N,N,N',N″,N″-pentamethyldiethylenetriamine) to give a benzyllithium 6-Li(l)·PMDTA that incorporates a trigonal planar secondary carbanion. In the solid state, the amide directing group and the PMDTA additive work together to abstract the metal ion from the deprotonated α-C of the propyl group (4.107(4) Å). A short distance of 1.376(3) Å is observed between the deprotonated carbon centre and a planar aromatic system that shows a pattern of bond lengths which contrasts with that reported for related tertiary carbanion systems. Analogous benzylic deprotonation is seen if 6-H is treated with t-BuLi in the presence of diglyme to give 6-Li(l)·DGME. X-ray crystallography now shows that the metal ion more closely approaches the tertiary carbanion (2.418(6) Å) but that the planarity of the deprotonated carbon centre and the bonding pattern in the organic anion seen in the PMDTA complex are retained. DFT analysis corroborates both the short distance between aromatic ring and carbanion centre and the unperturbed nature of aromaticity in 6-Li(l)·L (L = Lewis base). The observation of two structure-types for the carbanion in solution is explained theoretically and by NMR spectroscopy in terms of cis and trans isomerism imparted by partial double bond character in the arene-(α-C) bond.

Understanding metal concentration and speciation in motorway runoff.

Although highway runoff has historically been extensively studied, the increasing complexity of stormwater management means that there are still significant gaps regarding the reduction of soluble metals. The work reported in this paper addresses these challenges by analysing the presence and behaviour of iron, copper and zinc in runoff from junction 24 of the M1 motorway in the UK (peak traffic flow: 30,000 vehicles per hour) and comparing it with other urban sources of metals found in the same catchment (a local brook and sewage treatment works). The sampling site included an interceptor and a treatment lagoon and the event monitoring indicated a trend by which the metals did not change their concentration or particulate soluble proportion immediately, hence showing that pre- and post-storm conditions are important factors when analysing the solubility of metals and their behaviour. The data provided further evidence of the important influence of storm characteristics on metal concentrations in highway runoff, in particular the effects of an antecedent dry weather period (ADWP). In addition, this study also helped us to better understand how the release of sodium the application of de-icer for road maintenance in winter affects the availability of zinc.

Visible light photocatalysts from low-grade iron ore: the environmentally benign production of magnetite/carbon (Fe3O4/C) nanocomposites.

Magnetite (Fe3O4) nanoparticles coated with dextrose and gluconic acid possessing both super-paramagnetism and excellent optical properties have been productively synthesized through a straightforward, efficient and cost-efficient hydrothermal reduction route using Fe3+ as sole metal precursor acquired from accumulated iron ore tailings-a mining waste that usually represents a major environmental threat. Fe3O4/C nanocomposites were fully elucidated by FEGSEM and TEM, revealing a combination of platelets (<1 µm) capped by particles (<10 nm) and magnetite which was verified by XPS, which demonstrated also oxygen deficiency. A dextrose/gluconic acid coating was elucidated by Fourier transform-infrared (FT-IR) spectroscopy and thermogravimetric analysis (TGA). The Fe3O4/C nanocomposites were found to be superparamagnetic at room temperature. Meanwhile, their optical properties were investigated by UV-visible diffuse reflectance spectroscopy (UV-vis DRS) and photoluminescence (PL) spectroscopy; an Eg of 1.86 eV was determined, and emissions at 612 and 650 nm (ex. 250 nm) were consistent with the XPS identification of oxygen vacancies. The efficacy of the as-synthesized magnetically recoverable magnetite/carbon (Fe3O4/C) nanocomposites has been exhibited in the photocatalytic degradation of the toxic textile (industrial) dye bodactive red BNC-BS.

Ligand effects in the formation of tertiary carbanions from substituted tertiary aromatic amides.

Reaction of 2-isopropyl-(N,N-diisopropyl)-benzamide 5 with tBuLi in ether results in ortho deprotonation and the formation of a hemisolvate based on a tetranuclear dimer of (5-Li(o))(2)⋅Et(2)O. The solid-state structure exhibits a dimer core in which the amide oxygen atoms fail to stabilize the metal ions but are instead available for interaction with two metalated monomers that reside peripheral to the core. Reaction of 5 with tBuLi in the presence of the tridentate Lewis base PMDTA (N,N,N',N'',N''-pentamethyldiethylenetriamine) takes a different course. In spite of the tertiary aliphatic group at the 2-position in 5, X-ray crystallography revealed that a remarkable benzylic (lateral) deprotonation had occurred, giving the tertiary benzyllithium 5-Li(l)⋅PMDTA. The solid-state structure reveals that amide coordination and solvation by PMDTA combine to distance the Li(+) ion from the deprotonated α-C of the 2-iPr group (3.859(4) Å), thus giving an essentially flat tertiary carbanion and a highly distorted aromatic system. DFT analysis suggests that the metal ion resides closer to the carbanion center in solution. In line with this, the same (benzylic) deprotonation is noted if the reaction is attempted in the presence of tridentate diglyme, with X-ray crystallography revealing that the metal is now closer to the tertiary carbanion (2.497(4) Å). Electrophilic quenches of lithiated 5 have allowed, for the first time, the formation of quaternary benzylic substituents by lateral lithiation.

Deprotonative metalation of chloro- and bromopyridines using amido-based bimetallic species and regioselectivity-computed CH acidity relationships.

A series of chloro- and bromopyridines have been deprotometalated by using a range of 2,2,6,6-tetramethylpiperidino-based mixed lithium-metal combinations. Whereas lithium-zinc and lithium-cadmium bases afforded different mono- and diiodides after subsequent interception with iodine, complete regioselectivities were observed with the corresponding lithium-copper combination, as demonstrated by subsequent trapping with benzoyl chlorides. The obtained selectivities have been discussed in light of the CH acidities of the substrates, determined both in the gas phase and as a solution in THF by using the DFT B3LYP method.