Carbodicarbenes and Striking Redox Transitions of their Conjugate Acids: Influence of NHC versus CAAC as Donor Substituents.

Herein, a new type of carbodicarbene (CDC) comprising two different classes of carbenes is reported; NHC and CAAC as donor substituents and compare the molecular structure and coordination to Au(I)Cl to those of NHC-only and CAAC-only analogues. The conjugate acids of these three CDCs exhibit notable redox properties. Their reactions with [NO][SbF6 ] were investigated. The reduction of the conjugate acid of CAAC-only based CDC with KC8 results in the formation of hydrogen abstracted/eliminated products, which proceed through a neutral radical intermediate, detected by EPR spectroscopy. In contrast, the reduction of conjugate acids of NHC-only and NHC/CAAC based CDCs led to intermolecular reductive (reversible) carbon-carbon sigma bond formation. The resulting relatively elongated carbon-carbon sigma bonds were found to be readily oxidized. They were, thus, demonstrated to be potent reducing agents, underlining their potential utility as organic electron donors and n-dopants in organic semiconductor molecules.

Chalcogen Stabilized bis-Hydridoborate Complexes of Cobalt: Analogues of Tetracyclo[4.3.0.02,4 .03,5 ]nonane.

Treatment of Li[BH3 ER] (E=Se or Te, R=Ph; E=S, R=CH2 Ph) with [Cp*CoCl]2 led to the formation of hydridoborate complexes, [{CoCp*Ph}{Cp*Co}{µ-EPh}{µ-κ2 -E,H-EBH3 }], 1a and 1 b (1 a: E=Se; 1 b: E=Te) and a bis-hydridoborate species [Cp*Co{µ-κ2 -Se,H-SeBH3 }]2 , 2. All the complexes, 1 a, 1 b and 2 are stabilized by ß-agostic type interaction in which 1 b represents a novel bimetallic borate complex with a rare B-Te bond. QTAIM analysis furnished direct proof for the existence of a shared and dative B-chalcogen and Co-chalcogen interactions, respectively. In parallel to the formation of the hydridoborate complexes, the reactions also yielded tetracyclic species, [Cp*Co{κ3 -E,H,H-E(BH2 )2 -C5 Me5 H3 }], 3 a and 3 b (3 a: E=Se and 3 b: E=S), wherein the bridgehead boron atoms are surrounded by one chalcogen, one cobalt and two carbon atoms of a cyclopentane ring. Molecules 3 a and 3 b are best described as the structural mimic of tetracyclo[4.3.0.02,4 .03,5 ]nonane having identical structure and similar valence electron counts.

"Triple-Decker Sandwich" Containing Planar {B2E2Pd} Ring (E = S or Se).

In an effort to generate triple-decker complexes comprising a {PdCl2}moiety in the middle deck, we have explored the reactivity of [(Cp*M)2{µ-B2H2E2}], 1-4 (1: M = Co, E = S; 2: M = Co, E = Se; 3: M = Rh, E = Se; and 4: M = Ir, E = Se; Cp* = η5-C5Me5), with [PdCl2(COD)] (COD = 1,5-cyclooctadiene). The reactions led to the formation of a series of trinuclear heterometallic triple-decker complexes, [(Cp*M)2{µ-B2H2E2Pd(Cl)2}], 5-8 (5: M = Co, E = S; 6: M = Co, E = Se; 7: M = Rh, E = Se; and 8: M = Ir, E = Se). Formation of the complexes 5-8 occurred almost instinctively as a single product with the elimination of the COD ligand. These complexes are examples of novel triple-decker species having a planar bridging palladacycle ligand, in which the Pd metal exists as Pd(II) in an uncommon pseudo-octahedral environment with an elongated M-Pd bonding interaction. The new species, 5-8, have been characterized spectroscopically, and the structures of 5-7 were confirmed by single-crystal X-ray diffraction studies. The structure and bonding of these molecules were further analyzed with the help of density functional theory studies that found a strong electron donation from the B2E2 (E = S or Se) fragment of the middle ring to the axial metals, while a weak bonding interaction between group 9 metals and Pd.

Trithia-diborinane and Bis(bridging-boryl) Complexes of Ruthenium Derived from a [BH3(SCHS)]- Ion.

The field of diborinane is sparsely explored area, and not many compounds are structurally characterized. The room-temperature reaction of [{Cp*RuCl(µ-Cl)}2] (Cp* = η5-C5Me5) with Na[BH3(SCHS)] yielded ruthenium dithioformato [{Cp*Ru(µ,η3-SCHS)}2], 1, and 1-thioformyl-2,6-tetrahydro-1,3,5-trithia-2,6-diborinane complex, [(Cp*Ru){(η2-SCHS)CH2S2(BH2)2}], 2. To investigate the reaction pathway for the formation of 2, we carried out the reaction of [(BH2)4(CH2S2)2], 3, with 1 that yielded compound 2. To the best of our knowledge, it appears that compound 2 is the first example of a ruthenium diborinane complex where the central six-membered ring [CB2S3] adopts the chair conformation. Furthermore, room temperature reaction of 1 with [BH3·thf] resulted in the isolation of agostic-bis(σ-borate) complex, [Cp*Ru(µ-H)2BH(S-CH═S)], 4. Thermolysis of 4 with trace amount of tellurium powder led to formation of bis(bridging-boryl) complex, [{Cp*Ru(µ,η2-HBS2CH2)}2], 5, via dimerization of 4 followed by dehydrogenation. Compound 5 can be considered as a bis(bridging-boryl) species, in which the boryl units are connected to two ruthenium atoms. Theoretical studies and chemical bonding analyses demonstrate the reason for exceptional reactivity and stability of these complexes.

η(4) -HBCC-σ,π-Borataallyl Complexes of Ruthenium Comprising an Agostic Interaction.

Thermolysis of [Cp*Ru(PPh2 (CH2 )PPh2 )BH2 (L2 )] 1 (Cp*=η(5) -C5 Me5 ; L=C7 H4 NS2 ), with terminal alkynes led to the formation of η(4) -σ,π-borataallyl complexes [Cp*Ru(µ-H)B{R-C=CH2 }(L)2 ] (2 a-c) and η(2) -vinylborane complexes [Cp*Ru(R-C=CH2 )BH(L)2 ] (3 a-c) (2 a, 3 a: R=Ph; 2 b, 3 b: R=COOCH3 ; 2 c, 3 c: R=p-CH3 -C6 H4 ; L=C7 H4 NS2 ) through hydroboration reaction. Ruthenium and the HBCC unit of the vinylborane moiety in 2 a-c are linked by a unique η(4) -interaction. Conversions of 1 into 3 a-c proceed through the formation of intermediates 2 a-c. Furthermore, in an attempt to expand the library of these novel complexes, chemistry of σ-borane complex [Cp*RuCO(µ-H)BH2 L] 4 (L=C7 H4 NS2 ) was investigated with both internal and terminal alkynes. Interestingly, under photolytic conditions, 4 reacts with methyl propiolate to generate the η(4) -σ,π-borataallyl complexes [Cp*Ru(µ-H)BH{R-C=CH2 }(L)] 5 and [Cp*Ru(µ-H)BH{HC=CH-R}(L)] 6 (R=COOCH3 ; L=C7 H4 NS2 ) by Markovnikov and anti-Markovnikov hydroboration. In an extension, photolysis of 4 in the presence of dimethyl acetylenedicarboxylate yielded η(4) -σ,π-borataallyl complex [Cp*Ru(µ-H)BH{R-C=CH-R}(L)] 7 (R=COOCH3 ; L=C7 H4 NS2 ). An agostic interaction was also found to be present in 2 a-c and 5-7, which is rare among the borataallyl complexes. All the new compounds have been characterized in solution by IR, (1) H, (11) B, (13) C NMR spectroscopy, mass spectrometry and the structural types were unequivocally established by crystallographic analysis of 2 b, 3 a-c and 5-7. DFT calculations were performed to evaluate possible bonding and electronic structures of the new compounds.

Phase 2 trial of everolimus and carboplatin combination in patients with triple negative metastatic breast cancer.

INTRODUCTION: Rapamycin acts synergistically with platinum agents to induce apoptosis and inhibit proliferation in breast cancer cell lines. Combination of everolimus also known as RAD001 (oral mammalian target of rapamycin (mTOR) inhibitor) and carboplatin may have activity in metastatic triple-negative breast cancer (TNBC). METHODS: The primary objective of this study was to determine clinical benefit rate (CBR), that is (complete remission (CR) + partial remission (PR) + stable disease (SD) lasting ≥6 months) and the toxicity of everolimus/carboplatin in women with metastatic TNBC. Prior carboplatin was allowed. Treatment consisted of intravenous carboplatin area under the curve (AUC) 6 (later decreased to AUC 5 and subsequently to AUC 4) every 3 weeks with daily 5 mg everolimus. RESULTS: We enrolled 25 patients in this study. Median age was 58 years. There were one CR, six PRs, seven SDs and eight PDs (progression of disease). CBR was 36% (95% confidence interval (CI) 21.1 to 57.4%). One SD was achieved in a patient progressing on single agent carboplatin. The median progression free survival (PFS) was 3 months (95% CI 1.6 to 4.6 months) and overall survival (OS) was 16.6 months (95% CI 7.3 months to not reached). There were seven patients (28%) with ≥ grade 3 thrombocytopenia; three (12%) with grade 3 neutropenia (no bleeding/febrile neutropenia) and one (4%) with grade 3 anemia. Greater hematological toxicity was seen in the first seven patients treated with carboplatin AUC5/6. After the amendment for starting dose of carboplatin to AUC 4, the regimen was well tolerated with only one out of 18 patients with grade 3 neutropenia and two patients with grade 3 thrombocytopenia. There was only one case of mucositis. CONCLUSION: Everolimus-carboplatin was efficacious in metastatic TNBC. Dose limiting hematological toxicity was observed when AUC5/6 of carboplatin was combined with everolimus. However, carboplatin AUC 4 was well tolerated in combination with everolimus with continuing responses. TRIAL REGISTRATIONS: ClinicalTrials.gov NCT01127763.

The Role of County-Level Persistent Poverty in Stroke Mortality in the USA.

Stroke is a major health concern in the USA, disproportionately affecting socioeconomically disadvantaged groups. This study investigates the link between persistent poverty and stroke mortality rates in residents aged 65 and above, positing that sustained economic challenges at the county level correlate with an increase in stroke-related deaths. Persistent poverty refers to a long-term state where a significant portion of a population lives below the poverty threshold for an extended period, typically measured over several decades. It captures the chronic nature of economic hardship faced by a community across multiple generations. Utilizing data from the CDC Wonder database and the American Community Survey, we conducted a comprehensive analysis across US counties, differentiating them by persistent poverty status. Our results indicate a statistically significant link between persistent poverty and increased mortality from ischemic and hemorrhagic strokes; counties afflicted by long-standing poverty were associated with an additional 33.49 ischemic and 8.16 hemorrhagic stroke deaths per 100,000 residents annually compared to their wealthier counterparts. These disparities persisted when controlling for known stroke risk factors and other socioeconomic variables. These results highlight the need for targeted public health strategies and interventions to address the disparities in stroke mortality rates and the broader implications for healthcare equity. The study underscores the vital role of socioeconomic context in health outcomes and the urgency of addressing long-term poverty as a key determinant of public health.

The impact of historical redlining on neurosurgeon distribution and reimbursement in modern neighborhoods.

Background: This study examines the lasting impact of historical redlining on contemporary neurosurgical care access, highlighting the need for equitable healthcare in historically marginalized communities. Objective: To investigate how redlining affects neurosurgeon distribution and reimbursement in U.S. neighborhoods, analyzing implications for healthcare access. Methods: An observational study was conducted using data from the Center for Medicare and Medicaid Services (CMS) National File, Home Owner's Loan Corporation (HOLC) neighborhood grades, and demographic data to evaluate neurosurgical representation across 91 U.S. cities, categorized by HOLC Grades (A, B, C, D) and gentrification status. Results: Of the 257 neighborhoods, Grade A, B, C, and D neighborhoods comprised 5.40%, 18.80%, 45.8%, and 30.0% of the sample, respectively. Grade A, B, and C neighborhoods had more White and Asian residents and less Black residents compared to Grade D neighborhoods (p < 0.001). HOLC Grade A (OR = 4.37, 95%CI: 2.08, 9.16, p < 0.001), B (OR = 1.99, 95%CI: 1.18, 3.38, p = 0.011), and C (OR = 2.37, 95%CI: 1.57, 3.59, p < 0.001) neighborhoods were associated with a higher representation of neurosurgeons compared to Grade D neighborhoods. Reimbursement disparities were also apparent: neurosurgeons practicing in HOLC Grade D neighborhoods received significantly lower reimbursements than those in Grade A neighborhoods ($109,163.77 vs. $142,999.88, p < 0.001), Grade B neighborhoods ($109,163.77 vs. $131,459.02, p < 0.001), and Grade C neighborhoods ($109,163.77 vs. $129,070.733, p < 0.001). Conclusion: Historical redlining continues to shape access to highly specialized healthcare such as neurosurgery. Efforts to address these disparities must consider historical context and strive to achieve more equitable access to specialized care.

A phase 2 study of oxaliplatin combined with continuous infusion topotecan for patients with previously treated ovarian cancer.

BACKGROUND: Phase 2 trials suggest that prolonged intravenous (IV) infusion of the topoisomerase 1 inhibitor topotecan may be less toxic than when given by standard IV bolus 5-day administration. Oxaliplatin exhibits efficacy in platinum-pretreated disease and shows preclinical synergy with topoisomerase 1 inhibitors. We sought to determine the efficacy and safety of oxaliplatin plus infusion topotecan in recurrent platinum-pretreated ovarian cancer. METHODS: Patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancers previously treated with 1 to 2 prior regimens including platinum and taxane received oxaliplatin (85 mg/m(2) day 1 and day 15) and topotecan (0.4 mg/m(2) per day) by continuous IV infusion over 14 days every 4 weeks. The primary objective of the trial was to estimate the objective response rate in platinum-resistant disease (stratum 1) and in platinum-sensitive disease (stratum 2). Toxicities were assessed in all patients. RESULTS: Thirty-eight patients received 144 cycles of therapy (median, 4; range, 1-6). The most common grade 3 and grade 4 toxicities included thrombocytopenia (grade 3, 37%; and grade 4, 19%), neutropenia (grade 3, 37%; grade 4, 11%), and anemia (grade 3, 15%). Response occurred in 4 of 19 patients in stratum I (21%; 95% confidence intervals, 6%-46%) and 9 of 19 patients in stratum 2 (47%; 95% CI, 24%-71%). Three in each stratum had lengthy complete responses. CONCLUSIONS: Biweekly oxaliplatin plus a 14-day continuous IV infusion of topotecan, given monthly, is an active regimen in platinum-pretreated ovarian cancer and merits additional evaluation.

Analysis of factors associated with the failure of treatment in thoracolumbar burst fractures treated with short-segment posterior spinal fixation.

BACKGROUND: The treatment of thoracolumbar burst fractures continues to pose challenges. Although short-segment posterior spinal fixation (SSPSF) has shown satisfactory clinical outcomes, it is accompanied by a relatively high rate of treatment failure. This study aimed to assess factors associated with treatment failure in thoracolumbar burst fractures treated with SSPSF. METHODS: The clinical data of 241 consecutive patients with a traumatic thoracolumbar burst fracture who underwent SSPSF at our center between Apr 2016 and Apr 2021 were retrospectively reviewed. Patients were divided into two groups (failure of the treatment group and non-failure of the treatment group). We compared potential risk factors for the failure of treatment including age, gender, body mass index, smoking, diabetes, vertebral body compression rate, use of crosslinks, percentage of anterior height compression, presence of index level instrumentation, Cobb angle, interpedicular distance (IPD), canal compromise, Load Sharing Classification (LSC) score, use of posterolateral fusion, and pain intensity between the two groups. RESULTS: A sum of 137 (56.8%) males and 104 (43.2%) females were enrolled where the mean age and follow-up of the participants were 48.34 ± 10.23 years and 18.67 ± 5.23 months, respectively. Treatment failure was observed in 34 cases (14.1%). The results of the binary logistic regression analysis revealed that the lack of index level instrumentation (OR 2.21; 95% CI 1.78-3.04; P = 0.014), LSC score (odds ratio [OR] 2.64; 95% confidence interval [95% CI], 1.34-3.77; P = 0.007), and IPD (OR 1.77; 95% CI 1.51-2.67; P = 0.023) were independently associated with a higher rate of failure of treatment. CONCLUSIONS: The findings of this study revealed that increased rates of treatment failure in thoracolumbar burst fractures treated with SSPSF were associated with factors such as the absence of index level instrumentation, higher LSC scores, and larger IPD. These findings could be helpful in the proper management of patients with unstable thoracolumbar burst fractures.