A Meta-Analysis of the Impact of Resveratrol Supplementation on Markers of Renal Function and Blood Pressure in Type 2 Diabetic Patients on Hypoglycemic Therapy

Evidence on the beneficial effects of resveratrol supplementation on cardiovascular disease-related profiles in patients with type 2 diabetes (T2D) is conflicting, while its impact on renal function and blood pressure measurements remains to be established in these patients. The current meta-analysis included randomized controlled trials (RCTs) reporting on the impact of resveratrol supplementation on markers of renal function and blood pressure in patients with T2D on hypoglycemic medication. Electronic databases such as MEDLINE, Cochrane Library, Scopus, and EMBASE were searched for eligible studies from inception up to June 2020. The random and fixed effects model was used in the meta-analysis. A total of five RCTs met the inclusion criteria and involved 388 participants with T2D. Notably, most of the participants were on metformin therapy, or metformin in combination with other hypoglycemic drugs such as insulin and glibenclamide. Pooled estimates showed that resveratrol supplementation in patients with T2D lowered the levels of fasting glucose (SMD: −0.06 [95% CI: −0.24, 0.12]; I² = 4%, p = 0.39) and insulin (SMD: −0.08 [95% CI: −0.50, 0.34], I² = 73%, p = 0.002) when compared to those on placebo. In addition, supplementation significantly lowered systolic blood pressure (SMD: −5.77 [95% CI: −8.61, −2.93], I² = 66%, p = 0.02) in these patients. Although resveratrol supplementation did not affect creatinine or urea levels, it reduced the total protein content (SMD: −0.19 [95% CI: −0.36, −0.02]; I² = 91%, p = 0.001). In all, resveratrol supplementation in hypoglycemic therapy improves glucose control and lowers blood pressure; however, additional evidence is necessary to confirm its effect on renal function in patients with T2D.     

Reversible carbon–boron bond formation at platinum centers through σ-BH complexes

A reversible carbon–boron bond formation has been observed in the reaction of the coordinatively unsaturated, cyclometalated, Pt(ii) complex [Pt(I^tBuⁱPr′)(I^tBuⁱPr)][BAr^F], 1, with tricoordinated boranes HBR₂. X-ray diffraction studies provided structural snapshots of the sequence of reactions involved in the process. At low temperature, we observed the initial formation of the unprecedented σ-BH complexes [Pt(HBR₂)(I^tBuⁱPr′)(I^tBuⁱPr)][BAr^F], one of which has been isolated. From −15 to +10 °C, the σ-BH species undergo a carbon–boron coupling process leading to the platinum hydride derivative [Pt(H)(I^tBuⁱPr–BR₂)(I^tBuⁱPr)][BAr^F], 4. Surprisingly, these compounds are thermally unstable undergoing carbon–boron bond cleavage at room temperature that results in the 14-electron Pt(ii) boryl species [Pt(BR₂)(I^tBuⁱPr)₂][BAr^F], 2. This unusual reaction process has been corroborated by computational methods, which indicate that the carbon–boron coupling products 4 are formed under kinetic control whereas the platinum boryl species 2, arising from competitive C–H bond coupling, are thermodynamically more stable. These findings provide valuable information about the factors governing productive carbon–boron coupling reactions at transition metal centers.

A reversible carbon–boron bond formation has been observed in the reaction of the coordinatively unsaturated, cyclometalated, Pt(ii) complex [Pt(I^tBuⁱPr′)(I^tBuⁱPr)][BAr^F], 1, with tricoordinated boranes HBR₂.     

MicroRNA-134-5p and the Extent of Arterial Occlusive Disease Are Associated with Risk of Future Adverse Cardiac and Cerebral Events in Diabetic Patients Undergoing Carotid Artery Stenting for Symptomatic Carotid Artery Disease

There is little known about the prognostic value of serum microRNAs (miRs) in diabetic patients with symptomatic internal carotid artery disease (ICAS) who underwent stent supported angioplasty (PTA) for ICAS. The present study aimed to investigate expression levels of selected miRs for future major adverse cardiac and cerebral events (MACCE) as a marker in diabetic patients following ICAS-PTA. The expression levels of 11 chosen circulating serum miRs were compared in 37 diabetic patients with symptomatic ICAS and 64 control group patients with symptomatic ICAS, but free of diabetes. The prospective median follow-up of 84 months was performed for cardiovascular outcomes. Diabetic patients, as compared to control subjects, did not differ with respect to age (p = 0.159), distribution of gender (p = 0.375), hypertension (p = 0.872), hyperlipidemia (p = 0.203), smoking (p = 0.115), coronary heart disease (p = 0.182), lower extremities arterial disease (LEAD, p = 0.731), and miRs expressions except from lower miR-16-5p (p < 0.001). During the follow-up period, MACCE occurred in 16 (43.2%) diabetic and 26 (40.6%) non-diabetic patients (p = 0.624). On multivariate Cox analysis, hazard ratio (HR) and 95% Confidence Intervals (95%CI) for diabetic patients associated with MACCE were miR-134-5p (1.12; 1.05–1.21, p < 0.001), miR-499-5p (0.16; 0.02–1.32, p = 0.089), hs-CRP (1.14; 1.02–1.28; p = 0.022), prior myocardial infarction (8.56, 1.91–38.3, p = 0.004), LEAD (11.9; 2.99–47.9, p = 0.005), and RAS (20.2; 2.4–167.5, p = 0.005), while in non-diabetic subjects, only miR-16-5p (1.0006; 1.0001–1.0012, p = 0.016), miR-208b-3p (2.82; 0.91–8.71, p = 0.071), and hypertension (0.27, 0.08–0.95, p = 0.042) were associated with MACCE. Our study demonstrated that different circulating miRs may be prognostic for MACCE in diabetic versus non-diabetic patients with symptomatic ICAS. Higher expression levels of miR-134 were prognostic for MACCE in diabetic patients, while higher expression levels of miR-16 were prognostic in non-diabetic patients.     

Antioxidant and Starch-Hydrolyzing Enzymes Inhibitory Properties of Striga-Resistant Yellow-Orange Maize Hybrids

Most of the health benefits derived from cereals are attributed to their bioactive compounds. This study evaluated the levels of the bioactive compounds, and the antioxidant and starch-hydrolyzing enzymes inhibitory properties of six pipeline Striga-resistant yellow-orange maize hybrids (coded AS1828-1, 4, 6, 8, 9, 11) in vitro. The maize hybrids were grown at the International Institute of Tropical Agriculture (IITA), Nigeria. The bioactive compounds (total phenolics, tannins, flavonoids, and phytate) levels, antioxidant (DPPH^• and ABTS^•+ scavenging capacity and reducing power) and starch-hydrolyzing enzymes (α-amylase and α-glucosidase) inhibitory activities of the maize hybrids were determined by spectrophotometry. At the same time, carotenoids were quantified using a reverse-phase HPLC system. The ranges of the bioactive compounds were: 11.25–14.14 mg GAE/g (total phenolics), 3.62–4.67 mg QE/g (total flavonoids), 3.63–6.29 mg/g (tannins), 3.66–4.31% (phytate), 8.92–12.11 µg/g (total xanthophylls), 2.42–2.89 µg/g (total β-carotene), and 3.17–3.77 µg/g (total provitamin A carotenoids). Extracts of the maize hybrids scavenged DPPH^• (SC₅₀: 9.07–26.35 mg/mL) and ABTS^•+ (2.65–7.68 TEAC mmol/g), reduced Fe³⁺ to Fe²⁺ (0.25 ± 0.64–0.43 ± 0.01 mg GAE/g), and inhibited α-amylase and α-glucosidase, with IC₅₀ ranges of 26.28–52.55 mg/mL and 47.72–63.98 mg/mL, respectively. Among the six clones of the maize hybrids, AS1828-9 had the highest (p < 0.05) levels of tannins and phytate and the strongest antioxidant and starch-hydrolyzing enzymes inhibitory activities. Significant correlations were observed between total phenolics and the following: ABTS^•+ (p < 0.01, r = 0.757), DPPH^• SC₅₀ (p < 0.01, r = −0.867), reducing power (p < 0.05, r = 0.633), α-amylase IC₅₀ (p < 0.01, r = −0.836) and α-glucosidase IC₅₀ (p < 0.05, r = −0.582). Hence, the Striga-resistant yellow-orange maize hybrids (especially AS1828-9) may be beneficial for alleviating oxidative stress and postprandial hyperglycemia.     

Dependence of the Ripeness Stage on the Antioxidant and Antimicrobial Properties of Walnut (Juglans regia L.) Green Husk Extracts from Industrial By-Products

Walnut green husk (WGH) is a waste generated by the walnut (Juglans regia L.) harvest industry. It represents a natural source of polyphenols, compounds with antioxidant and antimicrobial activities, but their activity could be dependent on the ripeness stage of the raw material. In this study, the effect of the different ripeness stages—open (OH) and closed (CH) husks—on the antioxidant and antimicrobial properties of WGH extracts were analyzed, emphasizing the influence of the extracts in inhibiting Escherichia coli growth. The ripeness stage of WGH significantly affected the antioxidant activity of the extracts. This was attributed to the different polyphenol profiles related to the mechanical stress when the husk opened compared to the closed sample. The antimicrobial activity showed inhibition of E. coli growth. OH-extracts at 96 µg/mL caused the lowest specific growth rate (µ_max = 0.003 h⁻¹) and the greatest inhibition percentage (I = 93%) compared to CH-extract (µ_max = 0.01 h⁻¹; I = 69%). The obtained results showed the potential of the walnut green husk, principally open husk, as an economical source of antioxidant and antimicrobial agents with potential use in the food industry.     

Biomimetic catalytic aerobic oxidation of C–sp(3)–H bonds under mild conditions using galactose oxidase model compound CuIIL

Developing highly efficient catalytic protocols for C–sp(3)–H bond aerobic oxidation under mild conditions is a long-desired goal of chemists. Inspired by nature, a biomimetic approach for the aerobic oxidation of C–sp(3)–H by galactose oxidase model compound Cu^IIL and NHPI (N-hydroxyphthalimide) was developed. The Cu^IIL–NHPI system exhibited excellent performance in the oxidation of C–sp(3)–H bonds to ketones, especially for light alkanes. The biomimetic catalytic protocol had a broad substrate scope. Mechanistic studies revealed that the Cu^I-radical intermediate species generated from the intramolecular redox process of Cu^IILH₂ was critical for O₂ activation. Kinetic experiments showed that the activation of NHPI was the rate-determining step. Furthermore, activation of NHPI in the Cu^IIL–NHPI system was demonstrated by time-resolved EPR results. The persistent PINO (phthalimide-N-oxyl) radical mechanism for the aerobic oxidation of C–sp(3)–H bond was demonstrated.

A biomimetic catalytic approach for the aerobic oxidation of C–sp(3)–H bonds using galactose oxidase model compound was developed. EPR showed that the Cu^I-radical intermediate species was critical for O₂ activation.     

Optimising the Polyphenolic Content and Antioxidant Activity of Green Rooibos (Aspalathus linearis) Using Beta-Cyclodextrin Assisted Extraction

Antioxidant activity associated with green rooibos infusions is attributed to the activity of polyphenols, particularly aspalathin and nothofagin. This study aimed to optimise β-cyclodextrin (β-CD)-assisted extraction of crude green rooibos (CGRE) via total polyphenolic content (TPC) and antioxidant activity assays. Response surface methodology (RSM) permitted optimisation of β-CD concentration (0–15 mM), temperature (40–90 °C) and time (15–60 min). Optimal extraction conditions were: 15 mM β-CD: 40 °C: 60 min with a desirability of 0.985 yielding TPC of 398.25 mg GAE·g⁻¹, metal chelation (MTC) of 93%, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging of 1689.7 µmol TE·g⁻¹, ferric reducing antioxidant power (FRAP) of 2097.53 µmol AAE·g⁻¹ and oxygen radical absorbance capacity (ORAC) of 11,162.82 TE·g⁻¹. Aspalathin, hyperoside and orientin were the major flavonoids, with quercetin, luteolin and chrysoeriol detected in trace quantities. Differences (p < 0.05) between aqueous and β-CD assisted CGRE was only observed for aspalathin reporting the highest content of 172.25 mg·g⁻¹ of dry matter for extracts produced at optimal extraction conditions. Positive, strong correlations between TPC and antioxidant assays were observed and exhibited regression coefficient (R²) between 0.929–0.978 at p < 0.001. These results demonstrated the capacity of β-CD in increasing polyphenol content of green rooibos.     

Delocalization tunable by ligand substitution in [L2Al]n− complexes highlights a mechanism for strong electronic coupling

Ligand-based mixed valent (MV) complexes of Al(iii) incorporating electron donating (ED) and electron withdrawing (EW) substituents on bis(imino)pyridine ligands (I₂P) have been prepared. The MV states containing EW groups are both assigned as Class II/III, and those with ED functional groups are Class III and Class II/III in the (I₂P⁻)(I₂P²⁻)Al and [(I₂P²⁻)(I₂P³⁻)Al]²⁻ charge states, respectively. No abrupt changes in delocalization are observed with ED and EW groups and from this we infer that ligand and metal valence p-orbitals are well-matched in energy and the absence of LMCT and MLCT bands supports the delocalized electronic structures. The MV ligand charge states (I₂P⁻)(I₂P²⁻)Al and [(I₂P²⁻)(I₂P³⁻)Al]²⁻ show intervalence charge transfer (IVCT) transitions in the regions 6850–7740 and 7410–9780 cm⁻¹, respectively. Alkali metal cations in solution had no effect on the IVCT bands of [(I₂P²⁻)(I₂P³⁻)Al]²⁻ complexes containing –PhNMe₂ or –PhF₅ substituents. Minor localization of charge in [(I₂P²⁻)(I₂P³⁻)Al]²⁻ was observed when –PhOMe substituents are included.

Organo-aluminum mixed-valent complexes combine properties of both organic and transition element mixed-valent compounds. This supports delocalized electronic structures that are structurally and electronically tunable.     

Nanostructured Lipid Carriers (NLC) for Biologically Active Green Tea and Fennel Natural Oils Delivery: Larvicidal and Adulticidal Activities against Culex pipiens

(1) Background: The control of mosquitoes with essential oils is a growing demand. (2) Methods: This study evaluated the novel larvicidal and adulticidal activity of fennel and green tea oils and their nanostructured lipid carriers (NLC) against Culex pipiens (C. pipiens) in the laboratory, field conditions and evaluated their effect against non-target organisms. SLN type II nanoformulations were synthesized and characterized using dynamic light scattering (DLS), zeta potential and transmission electron microscope. (3) Results: The synthesized NLCs showed spherical shaped, homogenous, narrow, and monomodal particle size distribution. The mortality percent (MO%) post-treatment (PT) with 2000 ppm for 24 h with fennel oil and NLC fennel (NLC-F) reached 85% (LC₅₀ = 643.81 ppm) and 100% (LC₅₀ = 251.71), whereas MO% for green tea oil and NLC green tea (NLC-GT) were 80% (LC₅₀ = 746.52 ppm) and 100% (LC₅₀ = 278.63 ppm), respectively. Field trial data showed that the larval reduction percent of fennel oil and NLC-F reached 89.8% and 97.4%, 24 h PT and the reduction percent of green tea oil and NLC-GT reached 89% and 93%, 24 h PT with persistence reached 8 and 7 days, for NLC-F and NLC-GT, respectively. The adulticidal effects showed that NLC-F and NLC-GT (100% mortality) were more effective than fennel and green tea oils (90.0% and 83.33%), with 24 h PT, respectively. Moreover, their reduction of adult density after spraying with LC₉₅ X2 for 15 min, with fennel oil, NLC-F, and green tea oil, NLC-GT were 83.6%, 100%, 79.1%, and 100%, respectively, with persistence (>50%) lasting for three days. The predation rate of the mosquitofish, Gambusia affinis, and the bug, Sphaerodema urinator, was not affected in both oil and its NLC, while the predation rate of the beetle, Cybister tripunctatus increased (66% and 68.3%) by green tea oil and NLC-GT, respectively. (4) Conclusions: NLCs nanoformulation encapsulated essential oils was prepared successfully with unique properties of size, morphology, and stability. In vitro larvicidal and adulticidal effects against C. pipiens supported with field evaluations have been performed using essential oils and their nanoformulations. The biological evaluation of nanoformulations manifested potential results toward both larvicidal and adulticidal compared to the essential oils themselves, especially NLC encapsulated fennel oil which had promising larvicidal and adulticidal activity.     

Bacterial Diversity Correlates with Overall Survival in Cancers of the Head and Neck,Liver, and Stomach

One in five cancers is attributed to infectious agents, and the extent of the impact on the initiation, progression, and disease outcomes may be underestimated. Infection-associated cancers are commonly attributed to viral, and to a lesser extent, parasitic and bacterial etiologies. There is growing evidence that microbial community variation rather than a single agent can influence cancer development, progression, response to therapy, and outcome. We evaluated microbial sequences from a subset of infection-associated cancers—namely, head and neck squamous cell carcinoma (HNSC), liver hepatocellular carcinoma (LIHC), and stomach adenocarcinoma (STAD) from The Cancer Genome Atlas (TCGA). A total of 470 paired tumor and adjacent normal samples were analyzed. In STAD, concurrent presence of EBV and Selemonas sputigena with a high diversity index were associated with poorer survival (HR: 2.23, 95% CI 1.26–3.94, p = 0.006 and HR: 2.31, 95% CI 1.1–4.9, p = 0.03, respectively). In LIHC, lower microbial diversity was associated with poorer overall survival (HR: 2.57, 95% CI: 1.2, 5.5, p = 0.14). Bacterial within-sample diversity correlates with overall survival in infection-associated cancers in a subset of TCGA cohorts.     

Lanthanide MOFs for inducing molecular chirality of achiral stilbazolium with strong circularly polarized luminescence and efficient energy transfer for color tuning

We present herein an innovative host–guest method to achieve induced molecular chirality from an achiral stilbazolium dye (DSM). The host–guest system is exquisitely designed by encapsulating the dye molecule in the molecule-sized chiral channel of homochiral lanthanide metal–organic frameworks (P-(+)/M-(−)-TbBTC), in which the P- or M-configuration of the dye is unidirectionally generated via a spatial confinement effect of the MOF and solidified by the dangling water molecules in the channel. Induced chirality of DSM is characterized by solid-state circularly polarized luminescence (CPL) and micro-area polarized emission of DSM@TbTBC, both excited with 514 nm light. A luminescence dissymmetry factor of 10⁻³ is obtained and the photoluminescence quantum yield (PLQY) of the encapsulated DSM in DSM@TbTBC is ∼10%, which is close to the PLQY value of DSM in dilute dichloromethane. Color-tuning from green to red is achieved, owing to efficient energy transfer (up to 56%) from Ln³⁺ to the dye. Therefore, this study for the first time exhibits an elegant host–guest system that shows induced strong CPL emission and enables efficient energy transfer from the host chiral Ln-MOF to the achiral guest DSM with the emission color tuned from green to red.

Homochiral Ln-MOFs are synthesized to encapsulate achiral dyes to induce strong circularly polarized luminescence with a luminescence dissymmetry factor of 10⁻³.     

Glypican-3-Targeted Alpha Particle Therapy for Hepatocellular Carcinoma

Glypican-3 (GPC3) is expressed in 75% of hepatocellular carcinoma (HCC), but not normal liver, making it a promising HCC therapeutic target. GC33 is a full-length humanized monoclonal IgG1 specific to GPC3 that can localize to HCC in vivo. GC33 alone failed to demonstrate therapeutic efficacy when evaluated in patients with HCC; however, we posit that cytotoxic functionalization of the antibody with therapeutic radionuclides, may be warranted. Alpha particles, which are emitted by radioisotopes such as Actinium-225 (Ac-225) exhibit high linear energy transfer and short pathlength that, when targeted to tumors, can effectively kill cancer and limit bystander cytotoxicity. Macropa, an 18-member heterocyclic crown ether, can stably chelate Ac-225 at room temperature. Here, we synthesized and evaluated the efficacy of [²²⁵Ac]Ac–Macropa–GC33 in mice engrafted with the GPC3-expressing human liver cancer cell line HepG2. Following a pilot dose-finding study, mice (n = 10 per group) were treated with (1) PBS, (2) mass-equivalent unmodified GC33, (3) 18.5 kBq [²²⁵Ac]Ac–Macropa–IgG1 (isotype control), (4) 9.25 kBq [²²⁵Ac]Ac–Macropa–GC33, and (5) 18.5 kBq [²²⁵Ac]Ac–Macropa–GC33. While significant toxicity was observed in all groups receiving radioconjugates, the 9.25 kBq [²²⁵Ac]Ac–Macropa–GC33 group demonstrated a modest survival advantage compared to PBS (p = 0.0012) and 18.5 kBq [²²⁵Ac]Ac–IgG1 (p = 0.0412). Hematological analysis demonstrated a marked, rapid reduction in white blood cells in all radioconjugate-treated groups compared to the PBS and unmodified GC33 control groups. Our studies highlight a significant disadvantage of using directly-labeled biomolecules with long blood circulation times for TAT. Strategies to mitigate such treatment toxicity include dose fractionation, pretargeting, and using smaller targeting ligands.     

Oxidative Stress Is Increased in Combined Oral Contraceptives Users and Is Positively Associated with High-Sensitivity C-Reactive Protein

Information concerning the mechanisms underlying oxidative stress and low-grade inflammation in young healthy women predisposing eventually to future diseases is scarce. We investigated the relationship of oxidative stress and high-sensitivity C-reactive protein (hsCRP) in fertile-age women by oral combined contraceptive (OC) use. Caucasian Italian healthy non-obese women (n = 290; 100 OC-users; 190 non-OC-users; mean age 23.2 ± 4.7 years) were analyzed. Blood hydroperoxides, as oxidative stress biomarkers, were assessed by Free Oxygen Radical Test (FORT). Serum hsCRP was determined by an ultra-sensitive method (hsCRP). Markedly elevated oxidative stress (≥400 FORT Units) was found in 77.0% of OC-users and 1.6% of non-OC-users, odds ratio (OR) = 209, 95% CI = 60.9–715.4, p < 0.001. Elevated hsCRP levels ≥ 2.0 mg/L, considered risky for cardiovascular diseases (CVDs), were found in 41.0% of OC-users and 9.5% of non-OC-users, OR = 6.6, 95%CI 3.5–12.4, p < 0.001. Hydroperoxides were strongly positively correlated to hsCRP in all women (r_s = 0.622, p < 0.001), in OC-users (r_s = 0.442, p < 0.001), and in non-OC-users (r_s = 0.426, p < 0.001). Women with hydroperoxides ≥ 400 FORT Units were eight times as likely to have hsCRP ≥ 2 mg/L. In non-OC-users only, hydroperoxides values were positively correlated with weight and body mass index, but negatively correlated with red meat, fish and chocolate consumption. Our research is the first finding a strong positive correlation of serum hydroperoxides with hsCRP, a marker of low-grade chronic inflammation, in young healthy women. Further research is needed to elucidate the potential role of these two biomarkers in OC-use associated side-effects, like thromboembolism and other CVDs.     

Backbonding contributions to small molecule chemisorption in a metal–organic framework with open copper(i) centers

Metal–organic frameworks are promising materials for applications such as gas capture, separation, and storage, due to their ability to selectively adsorb small molecules. The metal–organic framework Cu^I-MFU-4l, which contains coordinatively unsaturated copper(i) centers, can engage in backbonding interactions with various small molecule guests, motivating the design of frameworks that engage in backbonding and other electronic interactions for highly efficient and selective adsorption. Here, we examine several gases expected to bind to the open copper(i) sites in Cu^I-MFU-4l via different electronic interactions, including σ-donation, π-backbonding, and formal electron transfer. We show that in situ Cu L-edge near edge X-ray absorption fine structure (NEXAFS) spectroscopy can elucidate π-backbonding by directly probing excitations to unoccupied backbonding orbitals with Cu d-character, even for gases that participate in other dominant interactions, such as ligand-to-metal σ-donation. First-principles calculations based on density functional theory and time-dependent density functional theory additionally reveal the backbonding molecular orbitals associated with these spectroscopic transitions. The energies of the transitions correlate with the energy levels of the isolated small molecule adsorbates, and the transition intensities are proportional to the binding energies of the guest molecules within Cu^I-MFU-4l. By elucidating the molecular and electronic structure origins of backbonding interactions between electron rich metal centers in metal–organic frameworks and small molecule guests, it is possible to develop guidelines for further molecular-level design of solid-state adsorbents for energy-efficient separations of relevance to industry.

In situ near edge X-ray absorption fine structure spectroscopy directly probes unoccupied states associated with backbonding interactions between the open metal site in a metal–organic framework and various small molecule guests.     

Arylation of gem-difluoroalkenes using a Pd/Cu Co-catalytic system that avoids β-fluoride elimination

Pd^II/Cu^I co-catalyze an arylation reaction of gem-difluoroalkenes using arylsulfonyl chlorides to deliver α,α-difluorobenzyl products. The reaction proceeds through a β,β-difluoroalkyl–Pd intermediate that typically undergoes unimolecular β-F elimination to deliver monofluorinated alkene products in a net C–F functionalization reaction. However to avoid β-F elimination, we offer the β,β-difluoroalkyl–Pd intermediate an alternate low-energy route involving β-H elimination to ultimately deliver difluorinated products in a net arylation/isomerization sequence. Overall, this reaction enables exploration of new reactivities of unstable fluorinated alkyl–metal species, while also providing new opportunities for transforming readily available fluorinated alkenes into more elaborate substructures.

Pd^II/Cu^I co-catalyze a desulfitative arylation of aliphatic gem-difluoroalkenes in a radical arylation/migratory insertion sequence that avoids β-F elimination.     

Rhodium-catalysed tetradehydro-Diels–Alder reactions of enediynes via a rhodium-stabilized cyclic allene

Efficient methods for the synthesis of fused-aromatic rings is a critical endeavour in the creation of new pharmaceuticals and materials. A direct method for preparing these systems is the tetradehydro-Diels–Alder reaction, however this is limited by the need for harsh reaction conditions. A potential, but underdeveloped, route to these systems is via transition metal-catalysed cycloaromatisation of ene-diynes. Herein, tethered unconjugated enediynes have been shown to undergo a facile room-temperature Rh^I-catalysed intramolecular tetradehydro-Diels–Alder reaction to produce highly substituted isobenzofurans, isoindolines and an indane. Furthermore, experimental and computational studies suggest a novel mechanism involving an unprecedented and complex Rh^I/Rh^III/Rh^I/Rh^III redox cycle involving the formation of an unusual strained 7-membered rhodacyclic allene intermediate and a Rh^III-stabilized 6-membered ring allene complex.

Room temperature Rh-catalysed tetradehydro-Diels–Alder reaction via an unusual Rh-stabilised allene.     

Stabilizing a three-center single-electron metal–metal bond in a fullerene cage

Trimetallic carbide clusterfullerenes (TCCFs) encapsulating a quinary M₃C₂ cluster represent a special family of endohedral fullerenes with an open-shell electronic configuration. Herein, a novel TCCF based on a medium-sized rare earth metal, dysprosium (Dy), is synthesized for the first time. The molecular structure of Dy₃C₂@I_h(7)-C₈₀ determined by single crystal X-ray diffraction shows that the encapsulated Dy₃C₂ cluster adopts a bat ray configuration, in which the acetylide unit C₂ is elevated above the Dy₃ plane by ∼1.66 Å, while Dy–Dy distances are ∼3.4 Å. DFT computational analysis of the electronic structure reveals that the endohedral cluster has an unusual formal charge distribution of (Dy₃)⁸⁺(C₂)²⁻@C₈₀⁶⁻ and features an unprecedented three-center single-electron Dy–Dy–Dy bond, which has never been reported for lanthanide compounds. Moreover, this electronic structure is different from that of the analogous Sc₃C₂@I_h(7)-C₈₀ with a (Sc₃)⁹⁺(C₂)³⁻@C₈₀⁶⁻ charge distribution and no metal–metal bonding.

A novel trimetallic carbide clusterfullerene, Dy₃C₂@I_h(7)-C₈₀, was successfully synthesized and isolated, and the encapsulated Dy₃C₂ cluster adopts a bat ray configuration featuring an unprecedented three-center single-electron Dy–Dy–Dy bond.     

Validated Simple HPLC-UV Method for Mycophenolic Acid (MPA) Monitoring in Human Plasma. Internal Standardization: Is It Necessary?

The aim of the work was to prepare a simple but reliable HPLC-UV method for the routine monitoring of mycophenolic acid (MPA). Sample preparation was based on plasma protein precipitation with acetonitrile. The isocratic separation of MPA and internal standard (IS) fenbufen was made on Supelcosil LC-CN column (150 × 4.6 mm, 5 µm) using a mobile phase: CH₃CN:H₂O:0.5M KH₂PO₄:H₃PO₄ (260:700:40:0.4, v/v). UV detection was set at 305 nm. The calibration covered the MPA concentration range: 0.1–40 µg/mL. The precision was satisfactory with RSD of 0.97–7.06% for intra-assay and of 1.92–5.15% for inter-assay. The inaccuracy was found between −5.72% and +2.96% (+15.40% at LLOQ) and between −8.82% and +5.31% (+19.00% at LLOQ) for intra- and inter-assay, respectively, fulfilling acceptance criteria. After a two-year period of successful application, the presented method has been retrospectively calibrated using the raw data disregarding the IS in the calculations. The validation and stability parameters were similar for both calculation methods. MPA concentrations were recalculated and compared in 1187 consecutive routine therapeutic drug monitoring (TDM) trough plasma samples from mycophenolate-treated patients. A high agreement (r² = 0.9931, p < 0.0001) of the results was found. A Bland–Altman test revealed a mean bias of −0.011 μg/mL (95% CI: −0.017; −0.005) comprising −0.14% (95% Cl: −0.39; +0.11), whereas the Passing–Bablok regression was y = 0.986x + 0.014. The presented method can be recommended as an attractive analytical tool for medical (hospital) laboratories equipped with solely basic HPLC apparatus. The procedure can be further simplified by disapplying an internal standard while maintaining appropriate precision and accuracy of measurements.     

Enhancing the photothermal conversion of tetrathiafulvalene-based MOFs by redox doping and plasmon resonance

Near-infrared (NIR) photothermal materials hold great promise for use in several applications, particularly in photothermal therapy, diagnosis, and imaging. However, current NIR responsive materials often show narrow absorption bands and low absorption efficiency, and have long response times. Herein, we demonstrate that the NIR absorption of tetrathiafulvalene-based metal–organic frameworks (MOFs) can be tuned by redox doping and using plasmonic nanoparticles. In this work, a MOF containing redox-active tetrathiafulvalene (TTF) units and Dy-carboxylate chains was constructed, Dy-m-TTFTB. The NIR absorption of the as-synthesized Dy-m-TTFTB was further enhanced by Ag⁺ or I₂ oxidation, transforming the neutral TTF into a TTF˙⁺ radical state. Interestingly, treatment with Ag⁺ not only generated TTF˙⁺ radicals, but it also formed Ag nanoparticles (NPs) in situ within the MOF pores. With both TTF˙⁺ radicals and Ag NPs, Ag NPs@Dy-m-TTFTB was shown to exhibit a wide range of absorption wavelengths (200–1000 nm) and also a high NIR photothermal conversion. When the system was irradiated with an 808 nm laser (energy power of 0.7 W cm⁻²), Ag NPs@Dy-m-TTFTB showed a sharp temperature increase of 239.8 °C. This increase was higher than that of pristine Dy-m-TTFTB (90.1 °C) or I₂ treated I₃⁻@Dy-m-TTFTB (213.0 °C).

The photo-response of the redox-active metal–organic framework has been systematically tuned by incorporating plasmonic Ag nanoparticles and tetrathiafulvalene radicals, resulting in efficient near-infrared photothermal conversion materials.