Ammonium-directed dihydroxylation: metal-free synthesis of the diastereoisomers of 3-aminocyclohexane-1,2-diol

The ammonium-directed, metal-free oxidation of 3-(N,N-dibenzylamino)cyclohex-1-ene with mCPBA in the presence of either trichloroacetic acid or tosic acid has been used as the key step to facilitate the synthesis of all the diastereoisomers of 3-aminocyclohexane-1,2-diol, in >98% de in each case.     

Host-guest Assembly Based on γ-Cyclodextrin-functionalized Multiwalled Carbon Nanotubes for Rutin Electrochemical Sensing

Here, we report multiwalled carbon nanotubes (MWCNTs) functionalized with γ-cyclodextrins (γCD) as a novel electrochemical strategy for Rutin determination, showing superior performance than β-cyclodextrins (βCD) modified MWCNTs, suggesting an adequate environment for host-guest interactions. Under optimized conditions, the sensor showed a linear range of 39–975 nmol L⁻¹ and a limit of detection of 7 nmol L⁻¹. When tested with quercetin, catechin, and caffeine, the platform presented high selectivity with an interference response <10 %. The method was employed to quantify Rutin in spiked pharmaceutical and herbal extracts, providing recovery of 93–98.4 %. Also, HPLC-PDA confirmed the method‘s accuracy.     

High diversity on simple substrates: 1,4-dihalo-2-butenes and other difunctionalized allylic halides for copper-catalyzed S(N)2' reactions

Enantioselective allylic alkylation with an organomagnesium reagent catalyzed by copper thiophene carboxylate (CuTC) was carried out on difunctionalized substrates, such as commercially available 1,4-dichloro-2-butene and 1,4-dibromo-2-butene, and on similar compounds of higher substitution pattern of the olefin for the formation of all-carbon chiral quaternary centers. The high regioselectivity obtained throughout the reactions favored good regiocontrol for the addition of phenyl Grignard reagents. Other difunctionalized substrates (allylic ethers and allylic alcohols) also underwent asymmetric S(N)2' substitution.     

Remotely triggered liposome release by near-infrared light absorption via hollow gold nanoshells

An elusive goal for systemic drug delivery is to provide both spatial and temporal control of drug release. Liposomes have been evaluated as drug delivery vehicles for decades, but their clinical significance has been limited by slow release or poor availability of the encapsulated drug. Here we show that near-complete liposome release can be initiated within seconds by irradiating hollow gold nanoshells (HGNs) with a near-infrared (NIR) pulsed laser. Our findings reveal that different coupling methods such as having the HGNs tethered to, encapsulated within, or suspended freely outside the liposomes, all triggered liposome release but with different levels of efficiency. For the underlying content release mechanism, our experiments suggest that the microbubble formation and collapse due to the rapid temperature increase of the HGN is responsible for liposome disruption, as evidenced by the formation of solid gold particles after the NIR irradiation and the coincidence of a laser power threshold for both triggered release and pressure fluctuations in the solution associated with cavitation. These effects are similar to those induced by ultrasound and our approach is conceptually analogous to the use of optically triggered nano-"sonicators" deep inside the body for drug delivery. We expect HGNs can be coupled with any nanocarriers to promote spatially and temporally controlled drug release. In addition, the capability of external HGNs to permeabilize lipid membranes can facilitate the cellular uptake of macromolecules including proteins and DNA and allow for promising applications in gene therapy.     

Genetic, genomic and physiological state studies on single-needle bio-electrosprayed human cells

Bio-electrospraying, a non-contact jet-based direct cell engineering approach, was recently pioneered and demonstrated for handling a wide range of primary living cells. In those studies, post-treated cells were biologically assessed in comparison to several controls by way of flow cytometry. Although flow cytometry accurately assesses those viable populations of cells, subtle effects at a sub-cellular level could have been missed. Therefore, in the present study we demonstrate metaphase chromosome breakage studies carried out on single-needle bio-electrosprayed human T-lymphocytes, which are compared with several controls. The results indicate that post-treated T-lymphocytes do not demonstrate any increase in chromosome damage in comparison to control cells. These studies further validate bio-electrospraying as a technique with potential for clinical utility.     

Physicochemical properties of the high-field MRI-relevant [Gd(DTTA-Me)(H2O)2]- complex

To study the physicochemical properties of the DTTA chelating moiety (H4DTTA = diethylenetriaminetetraacetic acid = N,N'-[iminobis(ethane-2,1-diyl)]bis[N-(carboxymethyl)glycine]), used in several compounds proposed as magnetic resonance imaging (MRI) contrast agents, the methylated derivative H4DTTA-Me (N,N'-[(methylimino)bis(ethane-2,1-diyl)]bis[N-(carboxymethyl)glycine]) was synthesized. Protonation constants of the ligand were determined in an aqueous solution by potentimetry and (1)H NMR pH titration and compared to various DTTA derivatives. Stability constants were measured for the chelates formed with Gd(3+) (log K(GdL) = 18.60 +/- 0.10) and Zn(2+) (log K(ZnL) = 17.69 +/- 0.10). A novel approach of determining the relative conditional stability constant of two paramagnetic complexes in a direct way by (1)H NMR relaxometry is presented and was used for the Gd(3+) complexes [Gd(DTTA-Me)(H2O)2](-) (L1) and [Gd(DTPA-BMA)(H2O)] (L2) [K(L1/L2)*(at pH 8.3, 25 degrees C) = 6.4 +/- 0.3]. The transmetalation reaction of the Gd(3+) complex with Zn(2+) in a phosphate buffer solution (pH 7.0) was measured to be twice as fast for [Gd(DTTA-Me)(H2O)2](-) in comparison to that for [Gd(DTPA-BMA)(H2O)]. This can be rationalized by the higher affinity of Zn(2+) toward DTTA-Me(4-) if compared to DTPA-BMA(3-). The formation of a ternary complex with L-lactate, which is common for DO3A-based heptadentate complexes, has not been observed for [Gd(DTTA-Me)(H2O)2](-) as monitored by (1)H NMR relaxometric titrations. From the results, it was concluded that the heptadentate DTTA-Me(4-) behaves similarly to the commercial octadentate DTPA-BMA(3-) with respect to stability. The use of [Gd(DTTA-Me)(H2O)2](-) as an MRI contrast agent in vitro and in animal studies is conceivable, mainly at high magnetic fields, where an increase of the inner-sphere-coordination water actually seems to be the most certain way to increase the relaxivity.     

Synthetic and mechanistic aspects of a new method for ruthenium-metalation of porphyrins and Schiff-bases

A new method is presented for metalation of a wide range of free-base, neutral, cationic, and anionic porphyrins in refluxing dimethylformamide (DMF) using an easily prepared [Ru(DMF) 6](OTf) 3 complex, and comparisons are made with the more familiar metalation procedure using Ru 3(CO) 12. Both procedures generate Ru (II)(porp)(CO)L complexes (L = solvent); use of the Ru (III)-triflate precursor gives yields comparable to, or greater than, those obtained with the carbonyl, and generates no Ru-chlorin impurities. Mechanistic studies on the meso-tetraphenylporphyrin system reveal that the DMF furnishes the CO, which in the presence of essential water reduces the metal, and metalation likely occurs via a Ru (II)-CO species. Corresponding metalation of tetradentate Schiff-bases gives trans-[Ru (III)(Schiff- base)(DMF) 2]OTf complexes in yields of approximately 50%, a limitation being the accompanying hydrolysis of the Schiff-base through the presence of trace water.     

Single switch surface hopping for molecular dynamics with transitions

A trajectory surface hopping algorithm is proposed, which stems from a mathematically rigorous analysis of propagation through conical intersections of potential energy surfaces. Since nonadiabatic transitions are only performed when a classical trajectory attains one of its local minimal surface gaps, the algorithm is called single switch surface hopping. Numerical experiments for a two mode Jahn-Teller system are presented, which illustrate the asymptotic justification of the method as well as its good performance in the physically relevant parameter range.     

Some Poisson structures and Lax equations associated with the Toeplitz lattice and the Schur lattice

The Toeplitz lattice is a Hamiltonian system whose Poisson structure is known. In this paper, we unveil the origins of this Poisson structure and derive from it the associated Lax equations for this lattice. We first construct a Poisson subvariety H _n of GL _n (C), which we view as a real or complex Poisson–Lie group whose Poisson structure comes from a quadratic R-bracket on gl _n (C) for a fixed R-matrix. The existence of Hamiltonians, associated to the Toeplitz lattice for the Poisson structure on H _n , combined with the properties of the quadratic R-bracket allow us to give explicit formulas for the Lax equation. Then we derive from it the integrability in the sense of Liouville of the Toeplitz lattice. When we view the lattice as being defined over R, we can construct a Poisson subvariety H _n ^τ of U _n which is itself a Poisson–Dirac subvariety of GL _n ^R (C). We then construct a Hamiltonian for the Poisson structure induced on H _n ^τ , corresponding to another system which derives from the Toeplitz lattice the modified Schur lattice. Thanks to the properties of Poisson–Dirac subvarieties, we give an explicit Lax equation for the new system and derive from it a Lax equation for the Schur lattice. We also deduce the integrability in the sense of Liouville of the modified Schur lattice.