Alkali Metal Metal(ates) Containing Divalent Earth Abundant Transition Metals

Recent advances in cooperative chemistry have shown the enormous potential of main group heterobimetallic complexes for the functionalisation of aromatic molecules. Going beyond main group metal chemistry, here we provide an overview on the synthesis, structure and reactivity of bimetallic complexes which combine an alkali-metal (AM= Li, Na) with a divalent earth-abundant transition metal (M= Mn, Fe, Co, Ni), containing the utility silyl amide HMDS (HMDS = N(SiMe3)2). Advancing the understanding on how cooperative effects operate in these bimetallic (ate) systems, selected examples of their applications in deprotonative metalation are also discussed with special emphasis on the constitution of the metalated intermediates

Tuning NaCo(II) Bimetallic Cooperativity to Perform Co–H Exchange / C–F Bond Activation Processes in Polyfluoroarenes

Recent advances in cooperative chemistry have shown the potential of heterobimetallic complexes combining an alkali-metal with an earth abundant divalent transition metal for the functionalisation of synthetically relevant aromatic molecules via deprotonative metalation. Pairing sodium with cobalt (II), here we provide an overview of the reactivity of bimetallic [NaCo(HMDS)3] [HMDS = N(SiMe3)2] towards C-H and C-F functionalisation of a wide range of perfluorinated molecules. These studies also uncover the enormous potential of this heterobimetallic base to perform Co-H exchanges with excellent selectivity and exceptional stoichiometric control as well as shedding light on the key role played by the alkali-metal

Persistent microembolic signals in the cerebral circulation on transcranial Doppler after intravenous sulfur hexafluoride microbubble infusion

BACKGROUND AND PURPOSE: Microembolic signals (MES) are detectable by transcranial Doppler monitoring and associated with increased risk of first or recurrent ischemic stroke. MES detection can also illuminate stroke etiology and the effect of prophylactic treatment. MES detection cannot accurately distinguish between stroke‐related microemboli and ultrasound contrast agents. These agents contain microbubbles and are frequently used in neuro‐ and cardiovascular diagnostics. We aimed to assess how long after contrast infusion microbubbles are detectable by transcranial Doppler monitoring. METHODS: Ten healthy volunteers received an intravenous infusion of stabilized sulfur hexafluoride microbubbles (SonoVue®) for 30 minutes. The infusion was followed by continuous unilateral Doppler monitoring (TCD‐X, Atys Medical, Soucieu‐en‐Jarrest, France) for 3.5 hours. RESULTS: MES persisted for 12 to 77 minutes (median 40.5 minutes), and the frequency tended to decrease gradually until cessation. CONCLUSIONS: None of the subjects had detectable MES for more than 77 minutes after ultrasound contrast infusion. MES detection with the intent to detect stroke‐related microemboli should wait for at least this long after completed infusion.publishedVersio

Characteristics and predictors of stroke mimics in young patients in the norwegian tenecteplase stroke trial (NOR-TEST)

Background Several studies have shown that stroke mimics occur more often among young patients. Our aims were to identify the common mimics in young patients under the age of 60 years who received thrombolysis, to analyze the risk of hemorrhage after treatment with thrombolysis, and to identify risk factors and clinical parameters that might identify mimics in this group. Methods Norwegian Tenecteplase Stroke Trial was a phase-3 trial investigating safety and efficacy of tenecteplase vs. alteplase in patients with acute ischemic stroke. Patients diagnosed with either acute cerebral ischemia or transient ischemic attack were categorized as stroke group, and patients with any diagnosis other than ischemic stroke or transient ischemic attack as mimics group. Patients were grouped post-hoc into young (< 60 years) and old (≥ 60 years). Logistic regression analyses were performed with mimics vs. stroke as dependent variable to identify predictors of mimics. Results Of the 1091 patients included in the trial, 211 patients (19.3%) were under the age of 60 years. Out of the 1091 patients, 434 (39.8%) were female, median age 77 years (18–99 years), and median NIHSS was 4. Sixty-nine patients (32.7%) out of the 211 patients under the age of 60 were diagnosed as mimic. Mimics were significantly more frequent among the young (OR = 3.3, 32.7% vs. 12.8%, p = < 0.001). The most frequent mimics diagnoses among patients under 60 years of age were migraine (11.8%), no definite diagnosis (11.4%) and peripheral vertigo (3.3%). Mimics were independently associated with age < 50 years (OR = 4.97, p = < 0.001), not currently working/studying (OR = 3.38, p = 0.002) and not having aphasia on admission (OR = 2.95, p = 0.025). None of the mimics under the age of 60 years had symptomatic or asymptomatic intracerebral hemorrhage as a complication to thrombolysis. Conclusion We found significantly more mimics in the young, of which migraine was the most predominant diagnosis. Thrombolysis with alteplase or tenecteplase did not cause ICH in any mimics under 60 years.publishedVersio

Impaired cerebrovascular reactivity may predict delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

Introduction: Delayed cerebral ischemia (DCI) is a major cause of disability and death after aneurysmal subarachnoid hemorrhage. The literature suggests that impaired cerebrovascular reactivity (CVR) may be a predictor for DCI; still no CVR based prediction model has been developed. Increased knowledge about possible predictors of DCI can improve patient management in high-risk patients and allow for shorter hospital stay in low-risk patients. Method: CVR was examined in 42 patients with aneurysmal subarachnoid hemorrhage and 37 patients treated for unruptured intracranial aneurysm, using acetazolamide test with transcranial Doppler monitoring of blood flow velocities. Patients were followed for development of DCI, separated into clinical deterioration and radiographic infarction. Results: For all patients, regardless of aneurysm rupture status, CVR was on average 5.5 percentage points lower on the ipsilateral side of aneurysm treatment. Patients with clinical deterioration due to DCI had lower CVR than patients without DCI, and the difference was larger on the contralateral side (33.9% vs. 49.2%). Two prediction models were constructed for clinical deterioration due to DCI. The area under the receiver operating characteristic curve was 0.82 in the model using established predictors, and 0.86 in the model that also included CVR. Conclusion: Our findings support the hypothesis that impaired CVR may be an independent predictor of clinical deterioration due to DCI, and may assist in identifying patients at risk after aneurysmal subarachnoid hemorrhage. Ipsilateral CVR reduction occurs in all patients after aneurysm treatment, regardless of DCI development, thus highlighting the need to evaluate ipsi- and contralateral CVR separately.publishedVersio

Continuous Local Intra-Arterial Nimodipine for the Treatment of Cerebral Vasospasm

Vasospasm (VSP) is one of the major causes for prolonged neurologic deficit in patients with aneurysmal subarachnoid hemorrhage. Few case series have reported about continuous local intra-arterial nimodipine administration (CLINA) in refractory VSP. We report our experience with CLINA in a patient with refractory cerebral VSP.publishedVersio

Unlocking the Metalation Applications of TMP‐powered Fe and Co(II) bis(amides): Synthesis, Structure and Mechanistic Insights

Producción CientíficaTypified by LiTMP and TMPMgCl.LiCl, (TMP=2,2,6,6-tetramethylpiperidide), s-block metal amides have found widespread applications in arene deprotonative metalation. On the contrary, transition metal amides lack sufficient basicity to activate these substrates. Breaking new ground in this field, here we present the synthesis and full characterisation of earth-abundant transition metals M(TMP)2 (M=Fe, Co). Uncovering a new reactivity profile towards fluoroarenes, these amide complexes can promote direct M−H exchange processes regioselectively using one or two of their basic amide arms. Remarkably, even when using a perfluorinated substrate, selective C-H metalation occurs leaving C−F bonds intact. Their kinetic basicity can be boosted by LiCl or NBu4Cl additives which enables formation of kinetically activated ate species. Combining spectroscopic and structural studies with DFT calculations, mechanistic insights have been gained on how these low polarity metalation processes take place. M(TMP)2 can also be used to access ferrocene and cobaltocene by direct deprotonation of cyclopentadiene and undergo efficient CO2 insertion of both amide groups under mild reaction conditions.Swiss National Science Foundation (SNF) (projects numbers 206021_ 177033 and 188573), the University of Bern, the Irish Research Council (GOIPG/2021/88, M.M.), and the University of Valladolid (CONVREC-2021-221, M.N.P.-D.

Serum uri acid: neuroprotection in thrombolysis. The Bergen NORSTROKE study

<p>Abstract</p> <p>Background</p> <p>A possible synergic role of serum uric acid (SUA) with thrombolytic therapies is controversial and needs further investigations. We therefore evaluated association of admission SUA with clinical improvement and clinical outcome in patients receiving rt-PA, early admitted patients not receiving rt-PA, and patients admitted after time window for rt-PA.</p> <p>Methods</p> <p>SUA levels were obtained at admission and categorized as low, middle and high, based on 33° and 66° percentile values. Patients were categorized as patients admitted within 3 hours of symptom onset receiving rt-PA (rt-PA group), patients admitted within 3 hours of symptom onset not receiving rt-PA (non-rt-PA group), and patients admitted after time window for rt-PA (late group). Short-term clinical improvement was defined as the difference between NIHSS on admission minus NIHSS day 7. Favorable outcome was defined as mRS 0 - 3 and unfavorable outcome as mRS 4 - 6.</p> <p>Results</p> <p>SUA measurements were available in 1136 patients. Clinical improvement was significantly higher in patients with high SUA levels at admission. After adjustment for possible confounders, SUA level showed a positive correlation with clinical improvement (r = 0.012, 95% CI 0.002-0.022, p = 0.02) and was an independent predictor for favorable stroke outcome (OR 1.004; 95% CI 1.0002-1.009; p = 0.04) only in the rt-PA group.</p> <p>Conclusions</p> <p>SUA may not be neuroprotective alone, but may provide a beneficial effect in patients receiving thrombolysis.</p

Management of Acute Ischemic Stroke.

OBJECTIVES: Concise synthetic review of the state of the art of management of acute ischemic stroke. DATA SOURCES: Available literature on PubMed. STUDY SELECTION: We selected landmark studies, recent clinical trials, observational studies, and professional guidelines on the management of stroke including the last 10 years. DATA EXTRACTION: Eligible studies were identified and results leading to guideline recommendations were summarized. DATA SYNTHESIS: Stroke mortality has been declining over the past 6 decades, and as a result, stroke has fallen from the second to the fifth leading cause of death in the United States. This trend may follow recent advances in the management of stroke, which highlight the importance of early recognition and early revascularization. Recent studies have shown that early recognition, emergency interventional treatment of acute ischemic stroke, and treatment in dedicated stroke centers can significantly reduce stroke-related morbidity and mortality. However, stroke remains the second leading cause of death worldwide and the number one cause for acquired long-term disability, resulting in a global annual economic burden. CONCLUSIONS: Appropriate treatment of ischemic stroke is essential in the reduction of mortality and morbidity. Management of stroke involves a multidisciplinary approach that starts and extends beyond hospital admission

Applying Na/Co( ii ) bimetallic partnerships to promote multiple Co–H exchanges in polyfluoroarenes

Heterobimetallic base NaCo(HMDS)3 [HMDS = N(SiMe3)2] enables regioselective di-cobaltation of activated polyfluoroarenes under mild reaction conditions. For 1,3,5-C6H2X3 (X= Cl, F), NaCo(HMDS)3 in excess at 80 °C impressively induces the collective cleavage of five bonds (two C–H and three C–X) of the substrates via a cascade activation process that cannot be replicated by LiCo(HMDS)3 or KCo(HMDS)3