Ruthenium(II)-Catalyzed Oxidative Annulation of Imidazo[1,5-a]quinolin-2-iums Salts and Internal Alkynes via C-H Bond Activation.

Ruthenium(II)-catalyzed synthesis of π-conjugated fused imidazo[1,5-a]quinolin-2-ium derivatives have been achieved via C-H activation of quinoline-functionalized NHC (NHC=N-heterocyclic carbene) and oxidative coupling with internal alkynes. The reaction occurred with high efficiency, broad substrate scope, tolerates a wide range of functional groups and utilized into a gram-scale. Synthetic applications of the coupled product have been exemplified in the late-stage derivatization of various highly functionalized scaffolds. Moreover, most of the annulated products exhibit intense fluorescence and have potential applications in optoelectronic devices. Mechanistic studies have provided insights into the spectroscopic characterization of key five-membered ruthenacycle intermediate and Ru(0) sandwich species. Based on several control experiments, deuterium-kinetic isotope effect, and thermodynamic activation parameters the mechanistic finding demonstrated that fused imidazo-[1,5-a]quinolin-2-ium C(2)-H bond cleavage is the rate-determining step and ruling out the possibility of reductive elimination for controlling the rate of reaction.

Chemo- and Regioselective Catalytic Cross-Coupling Reaction of Ketones for the Synthesis of ß, γ-Disubstituted ß, γ-Unsaturated Ketones.

C-C bond forming reaction of ketone with aldehyde is well-studied for the synthesis of α, ß-unsaturated ketones, however, the reaction with two different ketones to unsaturated carbonyl compound has not yet been systematically studied. Probably due to the relatively low reactivity of ketones as electrophiles (aldol acceptors), its propensity for retro-aldol reaction. The reactions often suffer from unsatisfactory chemoselectivity (self- vs. crossed aldol products) and regioselectivity (thermodynamic vs. kinetic enolate). In this quest, we report here for the first time selective cross-coupling reaction of ketones to ß-branched ß, γ-unsaturated ketones by using ruthenium catalysis. Interestingly, single crossed aldol condensation products are formed even in reactions where a mixture of products is possible. Reaction is highly chemoselective, regioselective and produces H2 O as the only byproducts making the protocol environmentally benign. Method is compatible with a wide variety of sensitive functional group and applicable for even problematic aliphatic ketones as substrates. Notably, acetone was found as a three-carbon feedstock for the syntheses of simple ß, γ-unsaturated ketone compounds. The process can further be extended to the gram-scale reaction and late-stage functionalization of natural products. With the help of DFT calculations, several control experiments, and deuterium-labeling experiments, the mechanistic finding demonstrated that initial aldol-condensation of ketones to a ß, ß-disubstituted α, ß-unsaturated ketone, which further isomerizes to a ß, γ- unsaturated ketone via η3 -allyl ruthenium complex.

Facile synthesis of tetrahydroquinoline containing dithiocarbamate derivatives via one-pot sequential multicomponent reaction.

An efficient sequential multi-component method for the synthesis of tetrahydroquinoline containing dithiocarbamates has been developed. This reaction involved a boronic acid-catalysed reduction of quinolines to tertrahydroquinolines, followed by nucleophilic addition reaction with carbon disulphide to form dithiocarbamic acids and subsequent S-arylation via external base-free Chan-Evans-Lam coupling in a one-pot operation. The methodology is compatible with a wide variety of functional groups and also useful in the late-stage functionalization of pharmaceuticals. The dual role of the boronic acid as a catalyst (in the reduction of quinolines) and as a reagent (in the S-arylation) has been demonstrated for the first time herein.

Shrinking lung syndrome mimicking diaphragmatic palsy in systemic lupus erythematosus.

A 25-year-old woman presented with 1 year of progressive orthopnoea, initially explained as bilateral diaphragmatic paresis caused by seronegative myasthenia gravis. She required assisted ventilation and received pyridostigmine and corticosteroids. She had minimal (particularly proximal) symmetrical tetraparesis with apparent bilateral diaphragmatic weakness, but had normal sensation. Further investigation suggested an overlap myositis with shrinking lung syndrome from systemic lupus erythematosus. She improved following immunosuppression with pulse corticosteroids and rituximab, and at 3 months no longer needed bilevel positive airway pressure support.

Direct C(3)5-H Polyfluoroarylation of 2-Amino/alkoxy Pyridines Enabled by a Transient and Electron-deficient Palladium Intermediate.

Herein, we present an unprecedented azine-limited C5-H polyfluoroarylation of 2-aminopyridines enabled by a transient and electron-deficient perfluoroaryl-Pd species via C-H/C-H coupling. The protocol further allows C3(5)-H polyfluoroarylation of 2-alkoxypyridines guided by sterics and electronics for the first time. The late-stage C-H functionalization of drugs, drug derivatives, and natural product derivatives and synthesis of C5-aryl drug derivatives further demonstrated the method's utility. The preliminary mechanistic studies reveal that the synergistic combination of the bulky yet electrophilic perfluoroaryl-Pd species and the partial nucleophilicity of the C5-position of 2-amino/alkoxy-pyridines is the origin of reactivity and selectivity. Importantly, the first experimental evidence for the role of diisopropyl sulfide is provided.

Clinical and radiological spectrum of anti-myelin oligodendrocyte glycoprotein (MOG) antibody encephalitis: single-center observational study.

OBJECTIVE: The objective was to describe the clinical presentations, radiologic features, and outcomes of patients with autoimmune encephalitis associated with myelin oligodendrocyte glycoprotein antibody (MOG). BACKGROUND: During the past decade, the spectrum of the myelin oligodendrocyte glycoprotein antibody-associated diseases (MOGAD) has expanded. Recently, patients with MOG antibody encephalitis (MOG-E) who do not fulfill the criteria for ADEM have been reported. In this study, we aimed to describe the spectrum of MOG-E. METHODS: Sixty-four patients with MOGAD were screened for encephalitis-like presentation. We collected the clinical, radiological, laboratory, and outcome data of the patients who presented with encephalitis and compared it with the non-encephalitis group. RESULTS: We identified sixteen patients (nine males and seven females) with MOG-E. The median age of the encephalitis population was significantly lower than the non-encephalitis group (14.5 years (11.75-18) vs. 28 years (19.75-42), p = 0.0004). Twelve out of sixteen patients (75%) had fever at the time of encephalitis. Headache and seizure were present in 9/16 (56.2%) and 7/16 (43.75%) patients, respectively. FLAIR cortical hyperintensity was present in 10/16 (62.5%) patients. Supratentorial deep gray nuclei were involved in 10/16 (62.5%) patients. Three patients had tumefactive demyelination, and one patient had a leukodystrophy-like lesion. Twelve of 16 (75%) patients had a good clinical outcome. Patient with leukodystrophy pattern and other with generalized CNS atrophy showed a chronic progressive course. CONCLUSION: MOG-E can have heterogeneous radiological presentations. FLAIR cortical hyperintensity, tumefactive demyelination, and leukodystrophy-like presentations are novel radiological presentations associated with MOGAD. Though majority of MOG-E have a good clinical outcome, few patients can have chronic progressive disease even on immunosuppressive therapy.

Prevalence and determinants of post-stroke sleep disorders: a cross-sectional hospital-based study.

INTRODUCTION: Post-stroke sleep disorders (PSSD) are an important part of post-stroke disability. PSSD is neglected as a part of stroke rehabilitation. We aimed to study the prevalence and determinants of PSSD in a hospital based, single center setting. METHODS: In a cross-sectional study, adult patients (≥ 18 years) with stroke (one month to one year after the onset), were enrolled in the study. Demographic, clinical, radiological, and motor and functional disabilities were assessed. Sleep quality was assessed with Pittsburg Sleep Quality Index (PSQI) and STOP BANG questionnaire (for obstructive sleep apnea [OSA]). Patients with poor sleep quality (PSQI > 5) were analyzed for risk factors. RESULTS: A total of 103 patients were recruited in the study period (January 2021 to June 2022). The self-reported prevalence of PSSD was 16% which increased to 72% when the PSQI was administered. High risk of OSA was present in 33%. In bivariate analysis, factors associated with PSQI > 5 were involvement of ≥ 2 lobes, lower body mass index (BMI), worse modified Rankin Scale (mRS), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A) and Stroke Specific Quality of Life (SSQoL). In multivariate analysis, only depression was associated with PSQI > 5 (OR: 1.3 (1.0; 1.7); p-value = 0.03). CONCLUSION: PSSD had a prevalence of 72%. In multivariate analysis, the factor associated with PSQI > 5 was worse HAM-D score.

Idiopathic brachial plexopathy after pacemaker implant.

A middle-aged woman presented with symptomatic complete heart block and underwent an uneventful dual chamber pacemaker implantation. Three weeks post procedure, she developed left arm pain and weakness, with neurological localization to the lower trunk of left brachial plexus. Possibilities of traumatic compression by the device/leads or postoperative idiopathic brachial plexopathy were considered. After ruling out traumatic causes, she was started on oral steroids, to which she responded remarkably. This case highlights the importance of recognizing this rare cause of brachial plexopathy following pacemaker implantation, because not only does an expedited diagnosis and medical treatment lead to prompt recovery with minimal neurological deficits, but it also circumvents an unnecessary surgical re-exploration.

Site-Selective Deoxygenative Amination of Azine N-Oxides with Carbodiimides under Catalyst-, Activator-, Base-, and Solvent-Free Conditions.

An operationally simple method for synthesizing 2-amino azines via [3+2] dipolar cycloaddition of azine N-oxide with carbodiimide has been demonstrated. The reaction can proceed smoothly under simple heating conditions without any transition metal catalyst, activator, base, and solvent. This transformation demonstrates a broad substrate scope and produces CO2 as the only co-product. The applicability of this method is highlighted by the late-stage modification of bioactive molecules, including quinine, (±)-α-tocopherol, and tryptamine modified quinoline.

Phosphorus containing porous organic polymers: synthetic techniques and applications in organic synthesis and catalysis.

The phosphorus-containing porous organic polymer is a trending material for the synthesis of heterogeneous catalysts. Decades of investigations have established phosphines as versatile ligands in homogeneous catalysis. Recently, phosphine-based heterogeneous catalysts were synthesized to exploit the same electronic properties while leveraging extra stability and reusability. In the last few decades, the catalysts were applied in diverse organic transformations, including hydroformylation, hydrogenation, C-C, C-N and C-X coupling, hydrosilylation, oxidative-carbonylation reactions, and so on. However, even though these polymers possess a multifunctional character, they face multiple synthetic issues in controlling the pore size, increasing the surface area, and creating a single type of active site. This review summarizes the developments in this field over the last few decades, highlighting the current limitation and future scope.

Boric acid catalyzed chemoselective reduction of quinolines.

Boric acid promoted transfer hydrogenation of substituted quinolines to synthetically versatile 1,2,3,4-tetrahydroquinolines (1,2,3,4-THQs) was described under mild reaction conditions using a Hantzsch ester as a mild organic hydrogen source. This methodology is practical and efficient, where isolated yields are excellent and reducible functional groups are well tolerated in the N-heteroarene moiety. The reaction parameters and tentative mechanistic pathways are demonstrated by various control experiments and NMR studies. The present work can also be scaled up to obtain gram quantities and the utility of the developed process is illustrated by the transformation of 1,2,3,4-THQs into a series of biologically important molecules including the antiarrhythmic drug nicainoprol.

Mercury(II) Complexes of Anionic N-Heterocyclic Carbene Ligands: Steric Effects of the Backbone Substituent.

Mercury(II) complexes (Me-maloNHCDipp)HgCl (1b), (t-Bu-maloNHCDipp)HgCl (2b) and (t-Bu-maloNHCDipp)HgMe (2c) supported by anionic N-heterocyclic carbenes have been obtained in good yields from the reaction of the potassium salt of N-heterocyclic carbene ligand precursors and mercury(II) salts, HgCl2 and MeHgI. These molecules have been characterized by 1H-NMR, 13C-NMR and IR spectroscopy and elemental analysis. X-ray crystal structures of 1b and 2b are also presented. Interestingly, complex 1b is polymeric {(Me-maloNHCDipp)HgCl}n in the solid state, as a result of inter-molecular Hg-O contacts, and features rare three coordinate mercury sites with a T-shaped arrangement, whereas the (t-Bu-maloNHCDipp)HgCl (2b) is monomeric and has a linear, two-coordinate mercury center. The formation of T-shaped structure and the aggregation of complex 1b is attributable to the reduced steric demand of the N-heterocyclic carbene ligand backbone substituent.

Awareness regarding eye donation among staff of a tertiary eye care hospital in North India.

PURPOSE: To assess the awareness, knowledge and attitude regarding eye donation in staff of a tertiary eye care hospital in North India. METHODS: A prospective, cross-sectional study was conducted on the employees of a tertiary eye care centre (urban area) along with its four secondary centres (rural area). Socio-demographic profile, awareness, knowledge and attitude of 507 employees regarding eye donation were evaluated through a pretested, self-administered questionnaire. Knowledge-based questions were scored. RESULTS: Of the 507 participants, 327 (64.5%) participants were from medical/paramedical field (Group 1) and 180 (35.5%) were from non-medical field (Group 2). Awareness about eye donation was 99%. Twenty (3.95%) participants scored poor (0-8), 90 (17.75%) had a fair score (9-16) and 397 (78.30%) had a good score (17-24). Good knowledge was found in significantly more (P = 0.01) participants in Group 1 (77.37%) as compared to Group 2 (70.1%). Four hundred and fifty-seven (90.13%) participants were willing to pledge their eyes for donation, the prime motivational force being spreading vision to the blind [346 (68.24%)]. The perceived reasons for not pledging were religious [28 (5.52%)], thought of family getting upset [29 (5.72%)] and scepticism regarding proper usage of tissue [64 (12.62%)]. CONCLUSION: The study demonstrated that although there is a substantial awareness about eye donation, there are certain lacunae in the knowledge and perceptions among staff of an eye care hospital. With the correct knowledge and attitude, they can contribute by creating awareness and motivating the people for eye donation while carrying out their routine hospital activities.

Tumefactive acute disseminated encephalomyelitis.

Tumefactive demyelinating lesions are tumour-like presentations of acute demyelinating lesions. They have been described with multiple sclerosis only and not with other varieties of acquired demyelination like acute disseminated encephalomyelitis (ADEM). The uncertainty about the diagnosis at the onset of the disease in tumefactive ADEM makes it important that the physicians should be aware of this entity. Various radiological similarities with more sinister lesions like central nervous system gliomas or lymphomas may lead to this confusion. Appropriate supportive treatment with steroids and follow up is required in these cases to avoid unnecessary interventions.

Zinc-Mediated Carbene Insertion to C-Cl Bonds of Chloromethanes and Isolable Zinc(II) Isocyanide Adducts.

The zinc adduct {[HB(3,5-(CF3)2Pz)3]Zn}(+), which was generated from [HB(3,5-(CF3)2Pz)3]ZnEt and [Ph3C]{B[3,5-(CF3)2C6H3]4}, catalyzes the activation of C-halogen bonds of chloromethanes via carbene insertion. Ethyl diazoacetate serves as the carbene precursor. The presence of {[HB(3,5-(CF3)2Pz)3]Zn}(+) in the reaction mixture was confirmed by obtaining {[HB(3,5-(CF3)2Pz)3]Zn(CN(t)Bu)3}(+) using CN(t)Bu as a trapping agent. {[HB(3,5-(CF3)2Pz)3]Zn(CN(t)Bu)3}(+) loses one zinc-bound CN(t)Bu easily to produce five-coordinate {[HB(3,5-(CF3)2Pz)3]Zn(CN(t)Bu)2}(+).

Zinc(II)-Mediated Carbene Insertion into C-H Bonds in Alkanes.

The cationic zinc adduct {[HB(3,5-(CF3)2Pz)3]Zn(NCMe)2}ClO4 catalyzes the functionalization of tertiary, secondary, and primary C-H bonds of alkanes via carbene insertion. Ethyl diazoacetate serves as the :CHCO2Et carbene precursor. The counteranion, supporting ligand, and coordinating solvents affect the catalytic activity. An in situ generated {[HB(3,5-(CF3)2Pz)3]Zn}(+) species containing a bulkier {B[3,5-(CF3)2C6H3]4}(-) anion gives the best results among the zinc catalysts used.

Inducing single molecule magnetic behavior in a [Co4O4] cubane via a pronounced solvatomagnetic effect.

The pyrazole-based tridentate diol ligand 2-(1-(2-hydroxyethyl)-1H-pyrazol-3-yl)phenol (H2L) forms a cubane-type complex [Co4L4(MeOH)4] (1) that features a {Co4O4} core and four exogenous MeOH ligands. Electrospray ionization mass spectrometry suggests that the MeOH ligands are easily lost, and thermogravimetric analysis evinces a thermally induced release of those methanol molecules from solid material in the temperature range from 380 to 440 K. Desolvation was found to give rise to a pronounced solvatomagnetic effect that causes a switching of the spin ground state of the {Co4O4} core from diamagnetic to magnetic. Furthermore, the desolvated "naked" [Co4L4] cube (1*) shows slow relaxation of the magnetization and butterfly-like magnetic hysteresis at 2 K. A comparatively high relaxation barrier Ueff/kB = 64.4 K and a characteristic relaxation time τ0 = 3.8 × 10(-9) s for 1* have been derived from an Arrhenius plot. These findings thus demonstrate that the emergence of interesting magnetic properties in molecule-based materials can be triggered via a solvatomagnetic process, even for materials that in their solvated form have a diamagnetic (ST = 0) ground state.