Thioxobimanes.

Dioxobimanes, colloquially known as bimanes, are a well-established family of N-heterobicyclic compounds that share a characteristic core structure, 1,5-diazabicyclo[3.3.0]octadienedione, bearing two endocyclic carbonyl groups. By sequentially thionating these carbonyls in the syn and anti isomers of the known (Me,Me)dioxobimane, we were able to synthesize a series of thioxobimanes, representing the first heavy-chalcogenide bimane variants. These new compounds were extensively characterized spectroscopically and crystallographically, and their aromaticity was probed computationally. Their potential role as ligands for transition metals was demonstrated by synthesizing a representative gold(I)-thioxobimane complex.

Shining light on fluoride detection: a comprehensive study exploring the potential of coumarin precursors as selective turn-on fluorescent chemosensors.

In this study, we report a fluoride chemosensor based on the use of a non-fluorescent pre-coumarin, compound 1. This compound undergoes selective fluoride-triggered formation of coumarin 2, with a concomitant turn-on fluorescence signal. Although compound 1 exists as a mixture of alkene isomers (2 : 1 in favor of the E isomer), only the minor Z-isomer undergoes cyclization. Nonetheless, comprehensive computational and experimental studies provide evidence that in situ isomerization of E-1 to Z-1, followed by fluoride-triggered phenolate evolution and intramolecular cyclization, facilitates the generation of coumarin 2 in high yield. Moreover, this system is an effective turn-on fluorescence sensor for fluoride anions, which displays outstanding selectivity (limited response to other commonly occurring analytes), sensitivity (lowest reported limits of detection for this sensor class), and practicality (works in solution and on paper to generate both fluorometric and colorimetric responses). Ongoing efforts are focused on expanding this paradigm to other pre-coumarin scaffolds, which also undergo analyte-specific coumarin formation accompanied by turn-on fluorescence.

Reaction of FeaqII with Peroxymonosulfate and Peroxydisulfate in the Presence of Bicarbonate: Formation of FeaqIV and Carbonate Radical Anions.

Many advanced oxidation processes (AOPs) use Fenton-like reactions to degrade organic pollutants by activating peroxymonosulfate (HSO5-, PMS) or peroxydisulfate (S2O82-, PDS) with Fe(H2O)62+ (FeaqII). This paper presents results on the kinetics and mechanisms of reactions between FeaqII and PMS or PDS in the absence and presence of bicarbonate (HCO3-) at different pH. In the absence of HCO3-, FeaqIV, rather than the commonly assumed SO4•-, is the dominant oxidizing species. Multianalytical methods verified the selective conversion of dimethyl sulfoxide (DMSO) and phenyl methyl sulfoxide (PMSO) to dimethyl sulfone (DMSO2) and phenyl methyl sulfone (PMSO2), respectively, confirming the generation of FeaqIV by the FeaqII-PMS/PDS systems without HCO3-. Significantly, in the presence of environmentally relevant concentrations of HCO3-, a carbonate radical anion (CO3•-) becomes the dominant reactive species as confirmed by the electron paramagnetic resonance (EPR) analysis. The new findings suggest that the mechanisms of the persulfate-based Fenton-like reactions in natural environments might differ remarkably from those obtained in ideal conditions. Using sulfonamide antibiotics (sulfamethoxazole (SMX) and sulfadimethoxine (SDM)) as model contaminants, our study further demonstrated the different reactivities of FeaqIV and CO3•- in the FeaqII-PMS/PDS systems. The results shed significant light on advancing the persulfate-based AOPs to oxidize pollutants in natural water.

The Role of Common Alcoholic Sacrificial Agents in Photocatalysis: Is It Always Trivial?

Photocatalytic hydrogen production is proposed as a sustainable energy source. Simultaneous reduction and oxidation of water is a complex multistep reaction with high overpotential. Photocatalytic processes involving semiconductors transfer electrons from the valence band to the conduction band. Sacrificial substrates that react with the photochemically formed holes in the valence band are often used to study the mechanism of H2 production, as they scavenge the holes and hinder charge carrier recombination (electron-hole pairs). Here, we show that the desired sacrificial agent is one forming a radical that is a fairly strong reducing agent, and whose oxidized form is not a good electron acceptor that might suppress the hydrogen evolution reaction (HER). In an acidic medium, methanol was found to fulfill both these requirements better than ethanol and propan-2-ol in the TiO2 -(M0 -NPs) (M=Au or Pt) system, whereas in an alkaline medium, the alcohols exhibit a reverse order of activity. Moreover, we report that CH2 (OH)2 is by far the most efficient sacrificial agent in a nontrivial mechanism in acidic media. Our study provides general guidelines for choosing an appropriate sacrificial substrate and helps to explain the variance in the performance of alcohol scavenger-based photocatalytic systems.

1,1-diamino-2,2-dinitroethylenes are always zwitterions.

The nitration of tetraiodoethylene (7) yields 1,1-diiodo-2,2-dinitroethylene (8). The latter reacts with alkylamines 9 or alkyldiamines 11 to give the corresponding acyclic 1,1-diamino-2,2-dinitroethylenes 10 or their cyclic analogs 12, respectively. On the basis of liquid and solid-state (13)C and (15)N NMR data, x-ray analysis and ab initio calculations, we suggest that the title compounds are always zwitterionic and that the C(A)-C(N) bond is not a true double bond.

A dipodal bimane-ditriazole-diCu(II) complex serves as an ultrasensitive water sensor.

An ultrasensitive fluorescent water sensor based on a dipodal bimane-Cu(II) complex is reported here. This complex, which is non-fluorescent in the absence of water, demonstrates a remarkable turn-on fluorescence in the presence of extremely low (0.000786% v/v) concentrations of water, via highly selective water-induced displacement of copper and restoration of the innate bimane fluorescence.

Surface modifications of carbon nanodots reveal the chemical source of their bright fluorescence.

Fluorescent carbon nanodots (CNDs) have drawn increasing attention in recent years. These cost-effective and eco-friendly nanomaterials with bright fluorescence have been investigated as promising materials for electrooptic and bioimaging applications. However, the chemical source stimulating their strong fluorescence has not been completely identified to date. Depending on the chemical composition, two absorption peaks are observed in the visible range. In this study, we applied selected chemical modifications to CNDs in order to elucidate the correlation between the chemical structure and optical behavior of CNDs. Varying the amount of acetic acid in the synthesis process resulted in different effects on the absorbance and fluorescence photo-spectra. Specifically, at a low concentration (10%), the fluorescence is dramatically red shifted from 340 to 405 nm. Comprehensive characterization of the chemical modification by FTIR and XPS allows identification of the role of acetic acid in the reaction mechanism leading to the modified photoactivity. The functional group responsible for the 405 nm peak was identified as HPPT. We describe a chemical mechanism involving acetic acid that leads to an increased concentration of HPPT groups on the surface of the CNDs. Applying two additional independent chemical and consequently optical modifications namely solution pH and annealing on the nanodots further supports our proposed explanation. Understanding the molecular origin of CND fluorescence may promote the design and control of effective CND fluorescence in optical applications.

Discovery of Dolastatinol: A Synthetic Analog of Dolastatin 10 and Low Nanomolar Inhibitor of Tubulin Polymerization.

We developed a highly potent anticancer agent, dolastatinol, which is a methylene hydroxyl derivative of dolastatin 10. Dolastatinol is a synthetic analog of dolastatin 10, synthesized by a solid-phase peptide Fmoc chemistry protocol on 2-chlorotrityl chloride resin utilizing a pH-triggering self-immolative monosuccinate linker. The introduction of the C-terminus hydroxyl methylene functionality preserves the anticancer properties of the parent dolastatin 10, including strong suppression of the cell proliferation, migration, high cytotoxicity. Our research establishes a new facile route toward the further development of C-terminus-modified dolastatin-10-based microtubule inhibitors for anticancer treatment.

The FeII(citrate) Fenton reaction under physiological conditions.

The Fenton reaction of FeII(citrate) in the presence and absence of bicarbonate (HCO3-) is studied. It is found that the rate constant of the Fenton reaction (kobs) increases with increasing [citrate]. kobs also increase with increasing [HCO3-]; this effect is most significant at biological citrate concentrations. Methane and ethane gases are formed from (CH3)2SO when the Fenton reaction is carried out in the presence of large [citrate] due to the reaction of the citrate radical, (-2OC)CH2C(OH)(CO2-)CH(CO2-)/(-2OC)CH2C(O)(CO2-)CH2(CO2-) with (CH3)2SO. In the absence of citrate (CH3)2SO2 is the main product of the Fenton reaction. However, in the presence of 0.10 mM citrate, no (CH3)2SO2 is formed, some (CH3)SOOH is formed, along with a low yield of beta-ketoglutaric acid. Formation of (CH3)SOOH and beta-ketoglutaric acid are due to the citrate radical and FeIV(citrate). In the presence of bicarbonate formation of abundant beta-ketoglutaric acid confirms the formation of carbonate radical anion (CO3-). Thus, bicarbonate affects the mechanism and kinetics of the reaction dramatically. Hydroxyl radicals (OH) are not formed in the presence of bicarbonate and probably also not in its absence. These results point out that hydroxyl radicals, formed by the Fenton reaction, do not initiate oxidative stress in biological systems.

Carbonate-radical-anions, and not hydroxyl radicals, are the products of the Fenton reaction in neutral solutions containing bicarbonate.

The Fenton reaction, Fe(H2O)62+ + H2O2 → Oxidizing product, is of major importance in biology as the major cause of oxidative stress, and in advanced oxidation processes. It is commonly assumed that ·OH is the product of the Fenton reaction. The results presented herein point out that ·OH is indeed the oxidizing product in acidic solutions for [Fe(H2O)62+] > [H2O2]; FeIVaq is the active oxidizing product in neutral solutions; in slightly acidic solutions for [H2O2] > [Fe(H2O)62+] a mixture of ·OH and FeIVaq is formed. However CO3·- is the active oxidizing product in neutral solutions containing HCO3- even at low concentrations, i.e. under physiological conditions. The implications to our understanding of the origins of oxidative stress and of catalytic oxidations in advanced oxidation processes are discussed.

Peptide-Driven Targeted Drug-Delivery System Comprising Turn-On Near-Infrared Fluorescent Xanthene-Cyanine Reporter for Real-Time Monitoring of Drug Release.

Targeted drug delivery (TDD) is an efficient strategy for cancer treatment. However, the real-time monitoring of drug delivery is still challenging because of a pronounced lack of TDD systems capable of providing a near-infrared (NIR) fluorescence signal for the detection of drug-release events. Herein, a new TDD system, comprising a turn-on NIR fluorescent reporter attached to an anticancer drug and targeting peptide, is reported. This system provides both TDD and NIR fluorescence monitoring of drug-release events in target tissue. In this TDD system, a new carboxy-derivatized xanthene-cyanine (XCy) dye is attached to an anticancer drug, chlorambucil (CLB), through a hydrolytically cleavable ester linker and coupled to a targeting peptide, octreotide amide (OCTA), which is specific to somatostatin receptors SSTR-2 and STTR-5 overexpressed on many tumor cells. This OCTA-G-XCy-CLB (G: γ-aminobutyric acid) conjugate exhibits no detectable fluorescence, whereas, upon the hydrolytic cleavage of the ester linker, a bright NIR fluorescence appears at λ≈710 nm; this signals release of the drug. Real-time TDD monitoring is demonstrated for the example of the human pancreatic cancer cell line overexpressing SSTR-2 and STTR-5, in comparison with the noncancerous Chinese hamster ovary cell line, which contains a reduced number of these receptors.

(1)H NMR studies distinguish the water soluble metabolomic profiles of untransformed and RAS-transformed cells.

Metabolomic profiling is an increasingly important method for identifying potential biomarkers in cancer cells with a view towards improved diagnosis and treatment. Nuclear magnetic resonance (NMR) provides a potentially noninvasive means to accurately characterize differences in the metabolomic profiles of cells. In this work, we use (1)H NMR to measure the metabolomic profiles of water soluble metabolites extracted from isogenic control and oncogenic HRAS-, KRAS-, and NRAS-transduced BEAS2B lung epithelial cells to determine the robustness of NMR metabolomic profiling in detecting differences between the transformed cells and their untransformed counterparts as well as differences among the RAS-transformed cells. Unique metabolomic signatures between control and RAS-transformed cell lines as well as among the three RAS isoform-transformed lines were found by applying principal component analysis to the NMR data. This study provides a proof of principle demonstration that NMR-based metabolomic profiling can robustly distinguish untransformed and RAS-transformed cells as well as cells transformed with different RAS oncogenic isoforms. Thus, our data may potentially provide new diagnostic signatures for RAS-transformed cells.

1,3-dipolar cycloadditions of trimethylsilyldiazomethane revisited: steric demand of the dipolarophile and the influence on product distribution.

The 1,3-dipolar cycloaddition of trimethylsilyldiazomethane with alpha,beta-unsaturated esters was examined. The resulting 1-pyrazolines isomerize to regioisomeric 2-pyrazolines (a or b) or undergo desilylation (c). Acrylates yield only b or c. beta-Substituted dipolarophiles may yield all three types of products. This work demonstrates that the distribution of 2-pyrazoline products is highly dependent on the relative configuration of the substituents on the 1-pyrazoline intermediate.

Structures of pahayokolides A and B, cyclic peptides from a Lyngbya sp.

The isolation and structure elucidation of two cyclic peptides, pahayokolides A (1) and B (2), is described. Structural features determined for these compounds include a pendent N-acetyl-N-methyl leucine, both E- and Z-dehydrobutyrines, a homophenylalanine, and an unusual polyhydroxy amino acid that is most likely of mixed polyketide synthase/nonribosomal peptide synthase origin. These peptides were purified from a new species of cyanobacteria of the genus Lyngbya, which was isolated from a periphyton mat from the Florida Everglades.

Novel carboxylated pyrrole- and carbazole-based monomers. Synthesis and electro-oxidation features.

Carboxylated pyrrole (Pyr, a index)- and carbazole (Cbz, b index)-containing monomers 6-7a/b and 9a/b have been readily synthesized from the monobenzyl ester of L-glutamic acid and triamine 2 using Clauson-Kaas and amide coupling reactions. In contrast to Pyr-containing compounds 6-7a, and 9a, the three Cbz-containing monomers 6-7b, and 9b have been found electroactive and were successfully electropolymerized on a Pt electrode resulting in the deposition of corresponding insoluble electroconducting polyCOOH polyCbz-films poly(6-7b) and poly(9b).

Dynamic and static conformational analysis of acylated tetrahydrobenzazepines.

A detailed high-field NMR analysis of several acylated tetrahydrobenzazepines, supported by molecular mechanics calculations, indicates that the heterocyclic ring in these compounds exists in a chair conformation, with the carbonyl oriented anti to the aryl moiety in the dominant rotamer. Surprisingly, ring methylenes are typically diastereotopic at room temperature, as the barriers for the process of enantiomerization of the seven-membered ring are much higher than expected. It is shown that ring inversion is correlated (but not concerted) with rotation of the amide moiety, as the carbonyl is forced out of conjugation with the nitrogen in the transition state.

Crystal structure and rotational barrier of octakis(bromomethyl)naphthalene.

Octakis(bromomethyl)naphthalene (4) adopts in the crystal a chiral conformation with a helical central naphthalene core and the bromomethyl groups disposed in an alternate up-down "in" arrangement. According to MM3 calculations, this conformation is less stable than the corresponding all alternated "out" form, while B3LYP/LANL2DZ calculations suggest the opposite stability order. The topomerization barrier (16.0 kcal mol(-1)) is ascribed to an enantiomerization process requiring 180 degrees rotation of all the bromomethyl groups and reversal of the helical sense of the naphthalene core.

Polyethylated triptycene derivatives.

The octaethyl triptycenes 7 and 8 were synthesized by Diels-Alder reaction of the octaethylanthracene 4with the corresponding benzynes. Low-temperature NMR spectra of 7 and 8 are consistent with the presence of the fully alternated conformation "a" of C(2) symmetry. However, in the determined crystal structures, the compounds adopt a higher energy conformation with a pair of vicinal ethyls oriented in the same direction.