Exploiting activation and inactivation mechanisms in type I-C CRISPR-Cas3 for genome-editing applications.

Type I CRISPR-Cas systems utilize the RNA-guided Cascade complex to identify matching DNA targets and the nuclease-helicase Cas3 to degrade them. Among the seven subtypes, type I-C is compact in size and highly active in creating large-sized genome deletions in human cells. Here, we use four cryoelectron microscopy snapshots to define its RNA-guided DNA binding and cleavage mechanisms in high resolution. The non-target DNA strand (NTS) is accommodated by I-C Cascade in a continuous binding groove along the juxtaposed Cas11 subunits. Binding of Cas3 further traps a flexible bulge in NTS, enabling NTS nicking. We identified two anti-CRISPR proteins AcrIC8 and AcrIC9 that strongly inhibit Neisseria lactamica I-C function. Structural analysis showed that AcrIC8 inhibits PAM recognition through allosteric inhibition, whereas AcrIC9 achieves so through direct competition. Both Acrs potently inhibit I-C-mediated genome editing and transcriptional modulation in human cells, providing the first off-switches for type I CRISPR eukaryotic genome engineering.

Implementing a Doping Approach for Poly(methyl methacrylate) Recycling in a Circular Economy.

To mitigate pollution by plastic waste, it is paramount to develop polymers with efficient recyclability while retaining desirable physical properties. A recyclable poly(methyl methacrylate) (PMMA) is synthesized by incorporating a minimal amount of an α-methylstyrene (AMS) analogue into the polymer structure. This P(MMA-co-AMS) copolymer preserves the essential mechanical strength and optical clarity of PMMA, vital for its wide-ranging applications in various commercial and high-tech industries. Doping with AMS significantly enhances the thermal, catalyst-free depolymerization efficiency of PMMA, facilitating the recovery of methyl methacrylate (MMA) with high yield and purity at temperatures ranging from 150 to 210 °C, nearly 250 K lower than current industrial standards. Furthermore, the low recovery temperature permits the isolation of pure MMA from a mixture of assorted common plastics.

Cannabis use frequency and pain interference among people with HIV.

Cannabis is often used by people with HIV (PWH) for pain, yet study results are inconsistent regarding whether and how it affects pain. This study examines whether greater cannabis use frequency is associated with lower pain interference and whether cannabis use modifies the association of pain severity and pain interference among 134 PWH with substance dependence or a lifetime history of injection drug use. Multi-variable linear regression models examined the association between past 30-day cannabis use frequency and pain interference. Additional models evaluated whether cannabis use modified the association between pain severity and pain interference. Cannabis use frequency was not significantly associated with pain interference. However, in a model with interaction between cannabis use frequency and pain severity, greater cannabis use frequency attenuated the strength of the association between pain severity and pain interference (p = 0.049). The adjusted mean difference (AMD) in pain interference was +1.13, + 0.81, and +0.05 points for each 1-point increase in pain severity for those with no cannabis use, 15 days of use, and daily use, respectively. These findings suggest that attenuating the impact of pain severity on pain-related functional impairment is a potential mechanism for a beneficial role of cannabis for PWH.

Intravascular fasciitis of the scalp as a complication of ICP monitor placement: a case report and review of the literature.

BACKGROUND/IMPORTANCE: There are only 56 documented cases of intravascular fasciitis, a rare variant of nodular fasciitis. Of these cases, only 2 involved the scalp. This lesion is amenable to surgical resection, making it important to differentiate it from soft tissue malignancies of the scalp. CLINICAL PRESENTATION: We report an unusual case of intravascular fasciitis involving the scalp at the site of an intracranial pressure (ICP) monitor of a 13-year-old male patient. The lesion was surgically excised with no recurrence upon 1-month follow-up. CONCLUSION: Intravascular fasciitis is a benign, reactive proliferation of soft tissue that may arise at sites of prior trauma. It appears as a soft, painless, mobile lesion, and immunohistochemical studies are required to differentiate it from malignant lesions. The standard of care is surgical resection of the lesion.

Changes in Polar Lipid Composition in Balsam Fir during Seasonal Cold Acclimation and Relationship to Needle Abscission.

Needle abscission in balsam fir has been linked to both cold acclimation and changes in lipid composition. The overall objective of this research is to uncover lipid changes in balsam fir during cold acclimation and link those changes with postharvest abscission. Branches were collected monthly from September to December and were assessed for cold tolerance via membrane leakage and chlorophyll fluorescence changes at -5, -15, -25, -35, and -45 °C. Lipids were extracted and analyzed using mass spectrometry while postharvest needle abscission was determined gravimetrically. Cold tolerance and needle retention each significantly (p < 0.001) improved throughout autumn in balsam fir. There were concurrent increases in DGDG, PC, PG, PE, and PA throughout autumn as well as a decrease in MGDG. Those same lipids were strongly related to cold tolerance, though MGDG had the strongest relationship (R2 = 55.0% and 42.7% from membrane injury and chlorophyll fluorescence, respectively). There was a similar, albeit weaker, relationship between MGDG:DGDG and needle retention (R2 = 24.3%). Generally, a decrease in MGDG:DGDG ratio resulted in better cold tolerance and higher needle retention in balsam fir, possibly due to increased membrane stability. This study confirms the degree of cold acclimation in Nova Scotian balsam fir and presents practical significance to industry by identifying the timing of peak needle retention. It is suggested that MGDG:DGDG might be a beneficial tool for screening balsam fir genotypes with higher needle retention characteristics.

Perceived efficacy of extrusion of maxillary lateral incisors with aligners.

INTRODUCTION: This study aimed to assess the perceived efficacy of aligners (Invisalign; Align Technology, Santa Clara, Calif) at performing extrusive movements of maxillary lateral incisors and to evaluate and compare differences in treatment planning protocols and other interventions used when required between orthodontists and general dentists with various degrees of experience. METHODS: An original 18-question survey was sent by mail to a randomized and geographically proportionate selection of orthodontic specialists (N = 400) and general dentists (N = 400) listed as providers on the Invisalign Web site. The data were analyzed using analysis of variance and chi-square tests. RESULTS: One hundred twenty-six providers responded to the survey (15.8% response rate), including 36 general dentists and 90 orthodontists. Overall, the average perceived efficacy was 4.71 out of 10 (95% confidence interval, 4.28-5.14). The threshold for identification of tracking issues was significantly associated with provider type (P = 0.0305). General dentists were significantly more likely to prefer an optimized attachment (P = 0.0001), whereas orthodontists were significantly more likely to prefer a gingivally-beveled horizontal rectangular attachment (P <0.0001). A refinement scan was the most common intervention method, followed by the bootstrap technique. CONCLUSIONS: The average perceived efficacy for extruding maxillary lateral incisors with aligners was 4.71 out of 10. Orthodontists had a lower tolerance than general dentists for tracking issues. A refinement scan was the most common method of intervention. General dentists and orthodontists differed in their treatment planning preferences and timing of intervention.

Effects of a Short-Term Heat Acclimation Protocol in Elite Amateur Boxers.

ABSTRACT: Stone, BL, Ashley, JD, Skinner, RM, Polanco, JP, Walters, MT, Schilling, BK, and Kellawan, JM. Effects of a short-term heat acclimation protocol in elite amateur boxers. J Strength Cond Res 36(7): 1966-1971, 2022-Boxing requires proficient technical and tactical skills coupled with high levels of physiological capacity. Although heat and humidity negatively affect acute exercise performance, short-term exercise training in hot and humid environments can lead to physiological adaptations that enhance exercise performance in both hot and thermoneutral conditions. In highly trained endurance athletes, exercise-induced acclimation can occur in as little as 5 days (known as short-term heat acclimation [STHA]). However, the impact of a 5-day heat acclimation (5-DayHA) in combat athletes, such as elite amateur boxers, is unknown. The aim of the present investigation was to determine whether a 5-DayHA improves aerobic performance in a thermoneutral environment and causes positive physiological adaptations in elite boxers. Seven elite amateur boxers underwent a 5-DayHA protocol, consisting of 60-minute exercise sessions in an environmental chamber at 32 °C and 70% relative humidity. Repeat sprint test (RST) evaluated aerobic performance in a thermoneutral environment 24 hours before and after the 5-DayHA. Presession and postsession hydration status (urine specific gravity) and body mass were assessed. After a 5-DayHA period, boxers significantly improved RST performance (13 ± 7 to 19 ± 7 sprints, d = 0.92, p = 0.03) but not pre-exercise hydration status (1.02 ± 0.01 to 1.01 ± 0.01, d = 0.82, p = 0.07). Therefore, these findings suggest 5-DayHA enhances aerobic performance in elite-level amateur boxers and may provide a viable training option for elite combat athletes.

Speckle illumination SFDI for projector-free optical property mapping.

Spatial frequency domain imaging can map tissue scattering and absorption properties over a wide field of view, making it useful for clinical applications such as wound assessment and surgical guidance. This technique has previously required the projection of fully characterized illumination patterns. Here, we show that random and unknown speckle illumination can be used to sample the modulation transfer function of tissues at known spatial frequencies, allowing the quantitative mapping of optical properties with simple laser diode illumination. We compute low- and high-spatial frequency response parameters from the local power spectral density for each pixel and use a lookup table to accurately estimate absorption and scattering coefficients in tissue phantoms, in vivo human hand, and ex vivo swine esophagus. Because speckle patterns can be generated over a large depth of field and field of view with simple coherent illumination, this approach may enable optical property mapping in new form-factors and applications, including endoscopy.

Palladium-Catalyzed Intermolecular Acylative Heck Reactions with Imides as Acyl Electrophiles.

We disclose palladium-catalyzed, intermolecular, acylative Heck reactions that use imides as acyl electrophiles. The catalyst generated from [Pd(allyl)Cl]2 and DPEphos promotes the reaction between N-benzoylglutarimides and norbornene in the presence of silver phosphate. The acylative Heck reaction encompasses an array of N-benzoylglutarimide electrophiles that contain electron-donating, halogenated, and electron-withdrawing substituents to generate α,ß-unsaturated ketones in moderate to high yields (25-82%). The bicylic α,ß-unsaturated ketones are readily transformed into polycyclic architectures via thermal hetero-Diels-Alder reactions that occur by the dimerization of the α,ß-unsaturated ketones.

Sociodemographic disparities in non-diabetic hyperglycaemia and the transition to type 2 diabetes: evidence from the English Longitudinal Study of Ageing.

AIM: To explore whether there are social inequalities in non-diabetic hyperglycaemia (NDH) and in transitions to type 2 diabetes mellitus and NDH low-risk status in England. METHODS: Some 9143 men and women aged over 50 years were analysed from waves 2, 4, 6 and 8 (2004-2016) of the English Longitudinal Study of Ageing (ELSA). Participants were categorized as: NDH 'low-risk' [HbA1c < 42 mmol/mol (< 6.0%)], NDH [HbA1c 42-47 mmol/mol (6.0-6.4%)] and type 2 diabetes [HbA1c > 47 mmol/mol (> 6.4%)]. Logistic regression models estimated the association between sociodemographic characteristics and NDH, and the transitions from NDH to diagnosed or undiagnosed type 2 diabetes and low-risk status in future waves. RESULTS: NDH was more prevalent in older participants, those reporting a disability, those living in deprived areas and in more disadvantaged social classes. Older participants with NDH were less likely to progress to undiagnosed type 2 diabetes [odds ratio (OR) 0.27, 95% confidence interval (CI) 0.08, 0.96]. NDH individuals with limiting long-standing illness (OR 1.72, 95% CI 1.16, 2.53), who were economically inactive (OR 1.60, 95% CI 1.02, 2.51) or from disadvantaged social classes (OR 1.63, 95% CI 1.02, 2.61) were more likely to progress to type 2 diabetes. Socially disadvantaged individuals were less likely (OR 0.64, 95% CI 0.41, 0.98) to progress to NDH low-risk status. CONCLUSIONS: There were socio-economic differences in NDH prevalence, transition to type 2 diabetes and transition to NDH low-risk status. Disparities in transitions included the greater likelihood of disadvantaged social groups with NDH developing type 2 diabetes and greater likelihood of advantaged social groups with NDH becoming low-risk. These socio-economic differences should be taken into account when targeting prevention initiatives.

Serum concentrations of DDE, PCBs, and other persistent organic pollutants and mammographic breast density in Triana, Alabama, a highly exposed population.

INTRODUCTION: Although some persistent organic pollutants (POPs) are considered human carcinogens, results from studies evaluating exposures and breast cancer risk have been inconsistent, potentially related to varying ages at exposure. Additionally, few studies evaluated the association between POPs exposure and mammographic breast density (MBD), an intermediate biomarker of breast cancer risk. We carried out a cross-sectional study to investigate associations between serum POPs concentrations and MBD measured in 1998 in female residents of Triana, Alabama, in a predominately African American population with high POPs exposures, particularly to p,p'-DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane). METHODS: We measured lipid-adjusted serum concentrations (ng/g lipid) of p,p'-DDT and its main metabolite p,p'-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene), polychlorinated biphenyls (PCBs), ß-hexachlorocyclohexane (ß-HCCH), heptachlor epoxide, oxychlordane, trans-nonachlor, mirex, and aldrin for each woman in our study (n = 210). We also measured two MBD metrics, percent MBD (%MBD) and area of MBD (aMBD). Using adjusted Spearman correlation coefficients (rs) we evaluated correlations between %MBD and aMBD with individual POPs in the overall population and by age group (19-40, 41-54, and 55-91 years) and also estimated adjusted mean measures of MBD with 95% confidence intervals across tertiles of analytes using generalized linear models (GLM). We calculated p-values for multiplicative interaction by age group using GLM. Additional analyses excluded women with current hormone replacement therapy (HRT) use and evaluated early-life exposure (prior to age 18) during the heaviest contamination period in Triana (1947-90). RESULTS: Among all women, we found no correlation between p,p'-DDE and %MBD, but after age stratification and exclusion of HRT users, there was a suggestion of a difference by age group, with younger women having a weak positive correlation (rs = 0.12, p = 0.37) and older women having a weak negative correlation (rs = -0.12, p = 0.43); pinteraction = 0.06. In contrast, PCBs were weakly positively correlated with %MBD among all women, with the correlation magnitudes increasing after excluding current HRT users (rs-total PCBs = 0.17, p = 0.03). After age stratification and exclusion of HRT users, correlations for PCBs were higher among younger and middle-age women, with only a handful of these correlations being statistically significant. For ß-HCCH, the strongest finding was a negative correlation among older women (rs = -0.26, p = 0.07). Correlations were positive predominantly in the younger age group for heptachlor epoxide (rs = 0.27, p = 0.04), oxychlordane (rs = 0.35, p = 0.006), and trans-nonachlor (rs = 0.37, p = 0.003), and largely null for the middle and older age groups; pinteraction range: 0.03-0.05. Similar patterns were found in GLM analyses using tertiles of exposure and aMBD as the metric for MBD. Women exposed during the heaviest chemical contamination period in Triana prior to age 18 had positive correlations between %MBD and PCBs, heptachlor epoxide, mirex, oxychlordane, and trans-nonachlor. CONCLUSIONS: In this population, despite high exposures to p,p'-DDT and thus high serum concentrations of its main metabolite, p,p'-DDE, we did not find strong evidence of a positive association with MBD. In fact, there was some evidence of a negative association among older women for p,p'-DDE; a similar pattern was found for ß-HCCH. However, younger women with higher serum levels of PCBs, heptachlor epoxide, oxychlordane, and trans-nonachlor, who were likely exposed in early life, had higher MBD. These findings should be replicated in larger studies.

Altered expression of p63 isoforms and expansion of p63- and club cell secretory protein-positive epithelial cells in the lung as novel features of aging.

Aging is a key contributor for subclinical progression of late-onset lung diseases. Basal, club, and type II alveolar epithelial cells (AECs) are lung epithelial progenitors whose capacities of differentiation are extensively studied. The timely transition of these cells in response to environmental changes helps maintain the intricate organization of lung structure. However, it remains unclear how aging affects their behavior. This paper demonstrates that the protein expression profiles of a type II AEC marker, prosurfactant protein C (pro-SPC), and a basal cell marker, p63, are altered in the lungs of 14-mo-old versus 7- to 9-wk-old mice. Expression of NH2-terminal-truncated forms of p63 (ΔNp63), a basal cell marker, and claudin-10, a club cell marker, in cytoplasmic extracts of lungs of 14-mo-old mice was upregulated. In contrast, nuclear expression of full-length forms of p63 (TAp63) decreases with age. These alterations in protein expression profiles coincide with dramatic changes in lung functions including compliance. Whole tissue lysates of middle-aged versus aged rhesus monkey lungs display similar age-associated alterations in pro-SPC expression. An age-associated decrease of TAp63 in nuclear lysates was observed in aged monkey group. Moreover, the lungs of 14-mo-old versus 7- to 9-wk-old mice display a wider spreading of ΔNp63-positive CCSP-positive bronchiolar epithelial cells. This expansion did not involve upregulation of Ki67, a representative proliferation marker. Collectively, it is postulated that 1) this expansion is secondary to a transition of progenitor cells committed to club cells from ΔNp63-negative to ΔNp63-positive status, and 2) high levels of cytoplasmic ΔNp63 expression trigger club cell migration.

Epigenetics of Mucus Hypersecretion in Chronic Respiratory Diseases.

Asthma, chronic obstructive pulmonary disease, and cystic fibrosis are three chronic pulmonary diseases that affect an estimated 420 million individuals across the globe. A key factor contributing to each of these conditions is mucus hypersecretion. Although management of these diseases is vastly studied, researchers have only begun to scratch the surface of the mechanisms contributing to mucus hypersecretion. Epigenetic regulation of mucus hypersecretion, other than microRNA post-translational modification, is even more scarcely researched. Detailed study of epigenetic mechanisms, such as DNA methylation and histone modification, could not only help to better the understanding of these respiratory conditions but also reveal new treatments for them. Because mucus hypersecretion is such a complex event, there are innumerable genes involved in the process, which are beyond the scope of a single review. Therefore, the purpose of this review is to narrow the focus and summarize specific epigenetic research that has been conducted on a few aspects of mucus hypersecretion in asthma, chronic obstructive pulmonary disease, cystic fibrosis, and some cancers. Specifically, this review emphasizes the contribution of DNA methylation and histone modification of particular genes involved in mucus hypersecretion to identify possible targets for the development of future therapies for these conditions. Elucidating the role of epigenetics in these respiratory diseases may provide a breath of fresh air to millions of affected individuals around the world.

A mitochondrial delicacy: dynamin-related protein 1 and mitochondrial dynamics.

The constant physiological flux of mitochondrial fission and fusion is inextricably tied to the maintenance of cellular bioenergetics and the fluidity of mitochondrial networks. Yet, the intricacies of this dynamic duo remain unclear in diseases that encompass mitochondrial dysregulation. Particularly, the role of the GTPase fission protein dynamin-related protein 1 (Drp1) is of profound interest. Studies have identified that Drp1 participates in complex signaling pathways, suggesting that the function of mitochondria in pathophysiology may extend far beyond energetics alone. Research indicates that, in stressed conditions, Drp1 translocation to the mitochondria leads to elevated fragmentation and mitophagy; however, despite this, there is limited knowledge about the mechanistic regulation of Drp1 in disease conditions. This review highlights literature about fission, fusion, and, more importantly, discusses Drp1 in cardiac, neural, carcinogenic, renal, and pulmonary diseases. The therapeutic desirability for further research into its contribution to diseases that involve mitochondrial dysregulation is also discussed.

Thyroid hormone: a resurgent treatment for an emergent concern.

The story of thyroid hormone in human physiology is one of mixed emotions. Studying past literature on its use leads one to believe that it serves only a few functions in a handful of diseases. In reality, the pathophysiological role of thyroid hormone is an uncharted expanse. Over the past few decades, research on thyroid hormone has been understandably monopolized by studies of hypo- and hyperthyroidism and cancers. However, in our focused pursuit, we have neglected to observe its role in systems that are not so easily relatable. Recent evidence in lung disease suggests that the thyroid hormone is capable of preserving mitochondria in an indirect manner. This is an exciting revelation given the profound implications of mitochondrial dysfunction in several lung diseases. When paired with known links between thyroid hormone and fibrotic pathways, thyroid hormone-based therapies become more enticing for research. In this article, we inspect the sudden awareness surrounding thyroid hormone and discuss why it is of paramount importance that further studies scrutinize the potential of thyroid hormone, and/or thyromimetics, as therapies for lung diseases.

Crossover between Athermal Jamming and the Thermal Glass Transition of Suspensions.

The non-Newtonian flow behavior of thermal and athermal disordered systems of dispersed uniform particles at high densities have strikingly similar features. By investigating the flow curves of yield-stress fluids and colloidal glasses having different volume fractions, particle sizes, and interactions, we show that both thermal and athermal systems exhibit power-law scaling with respect to the glass and jamming point, respectively, with the same exponents. All yield-stress flow curves can be scaled onto a single universal curve using the Laplace pressure as the stress scale for athermal systems and the osmotic pressure for the thermal systems. Strikingly, the details of interparticle interactions do not matter for the rescaling, showing that they are akin to usual phase transitions of the same universality class. The rescaling allows us to predict the flow properties of these systems from the volume fraction and known material properties.

Detecting state changes for ecosystem conservation with long-term monitoring of species composition.

Effective conservation requires an understanding not only of contemporary vegetation distributions in the landscape, but also cognizance of vegetation transitions over time with the goal of maintaining persistence of all states within the landscape. Using a state and transition model framework, we investigated temporal transitions over 31 years in species composition among five upland swamp vegetation communities in southeastern Australia. We applied fuzzy clustering to document transitions across communities; evaluated the resilience and resistance of communities to change; and explored the relationship between ecosystem states and major environmental factors posited to structure the system. We also evaluated the predictive ability of an established vegetation dynamics model. We found that community composition remained stable or underwent reversible or directional transitions depending on the vegetation type. Wetter communities (Ti-tree thicket and Cyperoid heath) were more stable (i.e., resistant) while drier communities showed a greater propensity to transition (i.e., had lower resistance) under the observed disturbance regime (low variance fire intervals). The resilience of drier communities differed under this regime, with Banksia thicket showing reversible compositional change, while Restioid heath and Sedgeland showed directional change. In accord with an established conceptual model, we found that communities were distributed along a hydrological gradient. In addition, vegetation structure, along with light penetration to ground level, differentiated communities. However, internal dynamics of drier communities were complex: differences in fire regime (penultimate fire interval in 2014 and number of fires since 1965) were unable to predict differences in community membership among sites. Aspects of the fire regime are expected to be more important predictors if fire intervals vary more strongly among sites in the future. Fuzzy clustering of compositional data allows managers to track community transitions over time and facilitates planned interventions for conservation purposes.

Comparative profiling of well-defined copper reagents and precursors for the trifluoromethylation of aryl iodides.

A number of copper reagents were compared for their effectiveness in trifluoromethylating 4-iodobiphenyl, 4-iodotoluene, and 2-iodotoluene. Yields over time were plotted in order to refine our understanding of each reagent performance, identify any bottlenecks, and provide more insight into the rates of the reactions. Interestingly, differences in reactivity were observed when a well-defined [LCuCF3] complex was employed directly or generated in situ from precursors by published reports. Relative reactivities were also found to highly dependent on the nature of the iodoarenes.

Juvenile idiopathic arthritis and future risk for cardiovascular disease: a multicenter study.

OBJECTIVES: To evaluate the frequency of cardiovascular disease (CVD) and CVD risk factor development in adult patients previously diagnosed with juvenile idiopathic arthritis (JIA). METHOD: A cohort study was conducted utilizing patients at two academic institutions (cohorts 1 and 2). Each institution evaluated the common endpoint of CVD outcomes and CVD risk factor development in adults aged ≥ 30 years and at the 29-year follow-up from disease onset in cohorts 1 and 2, respectively, with comparison to control groups of similar age and sex. RESULTS: Cohort 1 included 41 patients with JIA and follow-up ≥ 30 years of age with comparison to 41 controls. Three patients (7%) had CVD, compared to one control (2%; p = 0.31). Cohort 2 included 170 patients with JIA and a median of 29 years of follow-up from disease onset with comparison to 91 controls. Two patients (2%) had CVD, compared to none of the controls (p = 0.29). The presence of CVD risk factors was found to be increased in the JIA group compared to the controls in three categories: family history of CVD (cohort 1), hypertension (cohort 2), and ever smokers (cohorts 2). CONCLUSIONS: There is no increase in CVD events in patients with JIA 29 years following disease onset when compared to the general population. As these cohorts age, it will be informative to evaluate whether this baseline risk remains present or a trend towards increasing CVD emerges. Continued longitudinal follow-up of these cohorts and larger population-based studies are needed to establish a definitive relationship between JIA and CVD.

Unsymmetrical N-Aryl-1-(pyridin-2-yl)methanimine Ligands in Organonickel(II) Complexes: More Than a Blend of 2,2'-Bipyridine and N,N-Diaryl-α-diimines?

The new organonickel complexes [(R-PyMA)Ni(Mes)X] [R-PyMA = N-aryl-1-(pyridin-2-yl)methanimine; aryl = phenyl, 2,6-Me2-, 3,5-Me2-, 2,4,6-Me3-, 2,6-iPr2-, 3,5-(OMe)2-, 2-NO2-4-Me-, 4-NO2-, 2-CF3-, and 2-CF3-6-F-phenyl; Mes = 2,4,6-trimethylphenyl; X = F, Cl, Br, or I] were obtained as approximate 1/1 cis and trans isomeric mixtures or pure cis isomers depending on the PyMA ligand and X. The [(R-PyMA)Ni(Mes)X] complexes with X = Br or Cl were directly synthesized from the precursors trans-[(PPh3)2Ni(Mes)X], while [(PyMA)Ni(Mes)X] derivatives with X = F or I were obtained from [(PyMA)Ni(Mes)Br] through X exchange reactions. Although density functional theory (DFT) calculations show a preference for the sterically favored cis isomers, both isomers could be observed in many cases; in three cases, even single crystals for X-ray diffraction could be obtained for the trans isomers. Possible intermediates for the isomerization were investigated by DFT calculations. All complexes were studied by multiple spectroscopic means, electrochemistry, and spectroelectrochemistry (for the reduction processes). The long-wavelength metal-to-ligand charge-transfer (MLCT) absorptions vary markedly with the R substituent of the ligand and the cathodic electrochemical potentials to a far smaller degree. Both are almost invariable upon variation of X. All of this is in line with Ni-based and π*-based lowest unoccupied molecular orbitals (LUMOs). In line with the unsymmetric character of the NPy^Nmethanimine ligand, electrochemistry and MLCT transitions seem to not correspond to the same type of π* LUMO, making these PyMA ligands more interesting than the symmetric heteroaromatic polypyridine ligands such as 2,2'-bipyridine (bpy; NPy^NPy) and N,N-diaryl-substituted aliphatic α-diimines (Nmethanimine^Nmethanimine) such as the diaza-1,3-butadienes (DAB). First attempts to use these complexes in Negishi-type cross-coupling reactions were successful.