Measurement of Near-Field Radiative Heat Transfer at Deep Sub-Wavelength Distances using Nanomechanical Resonators.

Near-field radiative heat transfer (NFRHT) measurements often rely on custom microdevices that can be difficult to reproduce after their original demonstration. Here we study NFRHT using plain silicon nitride (SiN) membrane nanomechanical resonators─a widely available substrate used in applications such as electron microscopy and optomechanics─and on which other materials can easily be deposited. We report measurements down to a minimal distance of 180 nm between a large radius of curvature (15.5 mm) glass radiator and a SiN membrane resonator. At such deep sub-wavelength distance, heat transfer is dominated by surface polariton resonances over a (0.25 mm)2 effective area, which is comparable to plane-plane experiments employing custom microfabricated devices. We also discuss how measurements using nanomechanical resonators create opportunities for simultaneously measuring near-field radiative heat transfer and thermal radiation forces (e.g., thermal corrections to Casimir forces).

Cleavage of an Aromatic C-C Bond in Ferrocene by Insertion of an Iridium Nitrido Nitrogen Atom.

The intermolecular cleavage of C-C bonds is a rare event. Herein, we report on a late transition-metal terminal nitrido complex, which upon oxidation undergoes insertion of the nitrido nitrogen atom into the aromatic C-C bond of ferrocene. This reaction path was confirmed through 15N and deuterium isotope labeling experiments of the nitrido complex and ferrocenium, respectively. Cyclic voltammetry and UV/vis spectroscopy monitoring of the reaction revealed that oxidation is the initial step, yielding the tentative radical cationic nitrido complex, which is experimentally supported by extended X and Q-band electron paramagnetic resonance (EPR) and ENDOR, UV/vis, vT 1H NMR, and vibrational spectroscopic data. Density functional theory (DFT) and multireference calculations of this highly reactive intermediate revealed an S = 1/2 ground state. The high reactivity can be traced to the increased electrophilicity in the oxidized complex. Based on high-level PNO-UCCSD(T) calculations and UV/vis kinetic measurements, it is proposed that the reaction proceeds by initial electrophilic exo attack of the nitrido nitrogen atom at the cyclopentadienyl ring and consecutive ring expansion to a pyridine ring.

γ-Sultam-cored N,N-ligands in the ruthenium(ii)-catalyzed asymmetric transfer hydrogenation of aryl ketones.

The synthesis of new enantiopure syn- and anti-3-(α-aminobenzyl)-benzo-γ-sultam ligands 6 and their application in the ruthenium(ii)-catalyzed asymmetric transfer hydrogenation (ATH) of ketones using formic acid/triethylamine is described. In particular, benzo-fused cyclic ketones afforded excellent enantioselectivities in reasonable time employing a low loading of the syn ligand-containing catalyst. A never-before-seen dynamic kinetic resolution (DKR) during reduction of a γ-keto carboxylic ester (S7) derivative of 1-indanone is realized leading as well to excellent induction.

P-stereogenic phospholanes or phosphorinanes from o-biarylylphosphines: two bridges not too far.

The discovery of a concise regiodivergent asymmetric route to nonclassical P-stereogenic 5- or 6-membered benzophosphacycles, under conditions-dependent radical (oxidative addition) versus anionic (S(N)Ar) benzannulation, is reported.

Medium-term Oncological Efficacy and Patient-reported Outcomes After Focal High-intensity Focused Ultrasound: The FOXPRO Trial.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI)/transrectal ultrasound (TRUS) fusion-guided high-intensity focused ultrasound (HIFU) is a focal treatment option for MRI-visible localized prostate cancer (PCa). High-quality evidence regarding the clinical efficacy remains limited. OBJECTIVE: To assess medium-term oncological efficacy along with patient-reported outcome measures (PROMs). DESIGN, SETTING, AND PARTICIPANTS: This prospective single-center cohort study was performed from 2014 to 2020. Patients with primary International Society of Urological Pathologists (ISUP) grade group (GG) ≤2 by combined MRI/TRUS fusion and systematic prostate biopsy and prostate-specific antigen (PSA) <10 ng/ml were included. INTERVENTION: MRI/TRUS fusion-guided focal HIFU therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the cancer-free rate of the HIFU-treated lesion by biopsy after 1 yr. Secondary endpoints included salvage treatment-free survival (STFS), metastasis-free survival (MFS), overall survival (OS), and PROMs according to International Consortium for Health Outcomes Measurement recommendations. RESULTS AND LIMITATIONS: Fifty patients were included (median [range] age 68 [48-80] yr; median PSA 6.5 [1.2-9.9] ng/ml; GG 1 54% [n = 27], and GG 2 46% [n = 23]). The median (range) PSA decrease from baseline to 12 mo was 51% (35.9-72.7%). In total, 37/50 patients (74%) underwent a 1-yr biopsy. PCa was detected in 23 patients (46%; GG 1 20% [n = 10]; GG >1 26% [n = 13]; infield 40% [n = 20]). At a median follow-up of 42 (13-73) mo, PCa was detected in 30 men (60%). Among all patients, 19 (38%) underwent salvage treatments (median [95% confidence interval] STFS 53 [44.3-61.7] mo). MFS and OS were 100% and 98%, respectively. The Expanded Prostate Cancer Index Composite-26 sexual domain decreased by 20.8 points (p = 0.372). CONCLUSIONS: MRI/TRUS-guided focal HIFU therapy results in complete cancer ablation in only half of the treated patients after 1 yr, with further recurrences at medium-term follow-up. A decline of potency occurs in a subset of patients. PATIENT SUMMARY: Focal image-guided high-intensity focused ultrasound therapy controls cancer in one of two patients. Its impact on urinary continence and erectile function is low.

Synthesis and reactivity of dinuclear copper(I) pyridine diimine complexes.

The reaction of a tethered pyridine diimine (PDI) ligand with copper(I) chloride yielded a µ-chlorido bridged cationic dicopper(I) PDI complex, which is a rare structural motif. The geometric constraint of the ligand is fostering attractive van der Waals interactions between the coplanar pyridine units. This is supported by an Atoms in Molecules (AIM) and NCI (non-covalent interaction) analysis. Reaction with carbon monoxide yields the corresponding mono- and dicarbonyl complexes, which display reversible binding of carbon monoxide. This equilibrium was studied by 13C-NMR exchange spectroscopy and complemented by DFT and LNO-CCSD(T) calculations.

Profiling the tuneable R-SMS-Phos structure in the rhodium(I)-catalyzed hydrogenation of olefins: the last stand?

A diversified family of enantiopure P-stereogenic "R-SMS-Phos" {R-SMS-Phos = 1,2-bis[(o-RO-phenyl)(phenyl)phosphino]ethane} ligands wherein R = branched or heteroatom-substituted alkyl, aralkyl, silyl, acyl, sulfonyl, etc. was screened for the Rh(I)-catalyzed hydrogenation of a representative set of olefinic substrates. This systematic and detailed investigation revealed a marked beneficial impact on enantioselectivity and catalyst activity in comparison to Knowles' ultimate DiPAMP {DiPAMP = 1,2-bis[(o-anisyl)(phenyl)phosphino]ethane} design. Mutant ligands with highly enhanced properties possessing particular features wherein the DiPAMP structure is found embedded were identified.

trans-Diastereoselective Ru(II)-Catalyzed Asymmetric Transfer Hydrogenation of α-Acetamido Benzocyclic Ketones via Dynamic Kinetic Resolution.

A highly efficient enantio- and diastereoselective catalyzed asymmetric transfer hydrogenation via dynamic kinetic resolution (DKR-ATH) of α,ß-dehydro-α-acetamido and α-acetamido benzocyclic ketones to ent- trans-ß-amido alcohols is disclosed employing a new ansa-Ru(II) complex of an enantiomerically pure syn- N, N-ligand, i.e. ent- syn-ULTAM-(CH2)3Ph. DFT calculations of the transition state structures revealed an atypical two-pronged substrate attractive stabilization engaging the commonly encountered CH/π electrostatic interaction and a new additional O═S═O···HNAc H-bond hence favoring the trans-configured products.

Stereopure Functionalized Benzosultams via Ruthenium(II)-Catalyzed Dynamic Kinetic Resolution-Asymmetric Transfer Hydrogenation.

A highly diastereo- and enantioselective Ru(II)-catalyzed dynamic kinetic resolution-asymmetric transfer hydrogenation (DKR-ATH) of α-(N-sulfonylimino) and α-(N-sulfonylamino) aryl ketones to 4-hydroxy-benzo-δ- and 3-(α-hydroxy-arylmethyl)-benzo-γ-sultams is presented. By employing enantiopure ansa-Ru[PipSO2DPEN(CH2)4Ph] cat. II with S/C = 10 000 in a HCO2H/Et3N binary mix, up to >99.9% ee and dr >99:1 are obtained with 100% conversion under mild conditions. Application to access the stereopure "structurally simplified TsDPEN" N,N-ligand syn-3-(α-aminobenzyl)-benzo-γ-sultam ("syn-ULTAM") and its structural isomer trans-4-amino-3-phenyl-benzo-δ-sultam (trans-4) is demonstrated.

Highly enantioselective transfer hydrogenation of fluoroalkyl ketones.

[Structure: see text] The asymmetric transfer hydrogenation of fluoroalkyl ketones mediated by [Ru(eta6-arene)((S,S)-R2NSO2DPEN)] catalysts using HCO2H-Et3N afforded the corresponding alcohols with high ee's and in excellent yields.

Efficient asymmetric syntheses of 1-phenyl-phosphindane, derivatives, and 2- or 3-oxa analogues: mission accomplished.

A highly enantioselective synthesis of unsubstituted 1-phenyl-phosphindane and its P-borane and P-oxide derivatives was effectively established via a new fluoride-triggered desilylative carbocyclization strategy. Preparation of the "oxygen atom-doped" 1-phenyl-3-oxa-1-phosphindane-P-borane analogue was otherwise achieved via a tandem P-α-iodination-intra-O-alkylation.

Asymmetric transfer hydrogenation of 1-naphthyl ketones by an ansa-Ru(II) complex of a DPEN-SO2N(Me)-(CH2)2(η(6)-p-Tol) combined ligand.

The first second-generation designer Ru(II) catalyst 1b featuring an enantiopure N,C-(N-ethylene-N-methyl-sulfamoyl)-tethered (DPEN-κ(2)N,N')/η(6)-toluene hybrid ligand is introduced. Using an S/C = 1000 in HCO2H-Et3N 5:2 transfer hydrogenation medium, secondary 1-naphthyl alcohols are obtained in up to >99.9% ee under mild conditions. Mechanistic factors are discussed.

Impact on hydrogenation catalytic cycle of the R groups' cyclic feature in "R-SMS-Phos".

A series of R-SMS-Phos ligands was evaluated in the Rh(I)-catalyzed hydrogenation of a set of olefins showing a marked influence of the cyclic nature and structure of the R groups. Overall, cPen- and Cy-SMS-Phos performed efficiently, while Ph- and Bn-SMS-Phos exhibited slower kinetics and furnished lower ee's also compared with C(6)F(5)CH(2)-SMS-Phos. The Rh(I)-(Cy-SMS-Phos) catalyst was screened under mild conditions displaying excellent enantioselectivities and high TOFs. Cases of catalysis under catalyst or substrate control were identified.

Heavyweight "R-SMS-Phos" ligands in the olefins' hydrogenation arena.

A series of enantiopure P-stereogenic 1,2-bis[(o-RO-phenyl)(phenyl)phosphino]ethane (R-SMS-Phos) ligands wherein R = i-Pr, i-Bu, t-Bu, 3-Pen, and CH(2)TMS was assessed in the Rh(I)-catalyzed hydrogenation of an indicative set of olefins. The best performing t-Bu-SMS-Phos ligand was screened against a wide range of representative classes of standard and new olefinic substrates such as dehydroamido esters, dehydro-alpha-amido-phosphonates, enamides, itaconates, acrylates, enol acetates, alpha-phosphonovinyl benzoates, alpha-(2-pyridyl N-oxide)styrenes, and alpha-(1-hydroxyliminoethyl)styrenes. Excellent enantioselectivities and high TOFs were attained under mild conditions.

Tetracysteine-tagged prion protein allows discrimination between the native and converted forms.

The conformational conversion of prion protein (PrP) from a native conformation to the amyloid form is a hallmark of transmissible spongiform encephalopathies. Conversion is usually monitored by fluorescent dyes, which bind generic amyloids and are less suited for living cell imaging. We report a new method for the synthesis of membrane-permeable and membrane-impermeable biarsenical reagents, which are then used to monitor murine PrP (mPrP) misfolding. We introduced tetracysteine (TC) tags into three different positions of mPrP, which folded into a native-like structure. Whereas mPrPs with a TC tag inserted at the N-terminus or C-terminus supported fibril formation, insertion into the helix 2-helix 3 loop inhibited conversion. We devised a quantitative protease-free method to determine the fraction of converted PrP, based on the ability of the fluorescein arsenical helix binder reagent to differentiate between the monomeric and fibrilized form of TC-tagged PrP, and showed that TC-tagged mPrP could be detected on transfected cells, thereby expanding the potential use of this method for the detection and study of conformational diseases.

Ligand-based NMR spectra demonstrate an additional phytoestrogen binding site for 17beta-hydroxysteroid dehydrogenase type 1.

The enzyme 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) has become an important drug target for breast cancer because it catalyzes the interconversion of estrone to the biologically more potent estradiol which also plays a crucial role in the etiology of breast cancer. Patients with an increased expression of the 17beta-HSD1 gene have a significantly worse outcome than patients without. Inhibitors for 17beta-HSD1 are therefore included in therapy development. Here we have studied binding of 17beta-HSD1 to substrates and a number of inhibitors using NMR spectroscopy. Ligand observed NMR spectra show a strong pH dependence for the phytoestrogens luteolin and apigenin but not for the natural ligands estradiol and estrone. Moreover, NMR competition experiments show that the phytoestrogens do not replace the estrogens despite their similar inhibition levels in the in vitro assay. These results strongly support an additional 17beta-HSD1 binding site for phytoestrogens which is neither the substrate nor the co-factor binding site. Docking experiments suggest the dimer interface as a possible location. An additional binding site for the phytoestrogens may open new opportunities for the design of inhibitors, not only for 17beta-HSD1, but also for other family members of the short chain dehydrogenases.

Study of the reaction of bulky aryllithium reagents with 3,4-dimethyl-2,5-diphenyl-1,3,2-oxazaphospholidine-2-borane derived from ephedrine.

The ring opening of enantiomerically pure 3,4-dimethyl-2,5-diphenyl-1,3,2-oxazaphospholidine-2-borane (1) with a variety of bulky aryllithium reagents was studied. Our results are not in total agreement with those obtained by others. In fact, several 2,6-disubstituted aryl groups were successfully appended to the phosphorus atom, furnishing the corresponding (N-ephedrino)phosphine boranes 2a-g with dr>99:1. However, when the attack on the phosphorus atom is hindered, deprotonation on the benzylic position occurs, leading to the formation of enantiomerically pure trans-(N-methylamino)(phenyl)(1-phenyl-1-propenyloxy)phosphine-P-borane (3). While the attack of 2,2'-dilithio-1,1'-biarenes leads to the corresponding (P-phenyl)phosphole derivatives (4i,j) and to [bis(N-ephedrino)](phenyl)phosphine-P-borane (5), the attack of 1,1'-dilithiometallocenes (M=Fe, Ru) leads to a separable diastereomeric mixture of 1,1'-bis[(N-ephedrino)(phenyl)phosphino-P-borane]metallocenes (2k,l/2k',l') with dr approximately 80:20.