The PET-Tracer Zr-Df-IAB22M2C Enables Monitoring of Intratumoral CD8 T-cell Infiltrates in Tumor-Bearing Humanized Mice after T-cell Bispecific Antibody Treatment.

CD8-expressing T cells are the main effector cells in cancer immunotherapy. Treatment-induced changes in intratumoral CD8 T cells may represent a biomarker to identify patients responding to cancer immunotherapy. Here, we have used a Zr-radiolabeled human CD8-specific minibody (Zr-Df-IAB22M2C) to monitor CD8 T-cell tumor infiltrates by PET.

Preclinical studies for a phase 1 clinical trial of autologous hematopoietic stem cell gene therapy for sickle cell disease.

Background Aims: Gene therapy by autologous hematopoietic stem cell transplantation (HSCT) represents a new approach to treat sickle cell disease (SCD). Optimization of the manufacture, characterization and testing of the transduced hematopoietic stem cell final cell product (FCP), as well as an in depth in vivo toxicology study, are critical for advancing this approach to clinical trials.

Methods: Data are shown to evaluate and establish the feasibility of isolating, transducing with the Lenti/β-FB vector and cryopreserving CD34 cells from human bone marrow (BM) at clinical scale.

Rational design of small molecule inhibitors targeting the Rac GTPase-p67(phox) signaling axis in inflammation.

The NADPH oxidase enzyme complex, NOX2, is responsible for reactive oxygen species production in neutrophils and has been recognized as a key mediator of inflammation. Here, we have performed rational design and in silico screen to identify a small molecule inhibitor, Phox-I1, targeting the interactive site of p67(phox) with Rac GTPase, which is a necessary step of the signaling leading to NOX2 activation. Phox-I1 binds to p67(phox) with a submicromolar affinity and abrogates Rac1 binding and is effective in inhibiting NOX2-mediated superoxide production dose-dependently in human and murine neutrophils without detectable toxicity.

Targeting rho GTPases by peptidic structures.

Rho GTPases represent a family of small GTP-binding proteins that are involved in many important cellular functions relevant to cancer including cell cytoskeleton organization, migration, transcription, and proliferation. Since deregulation of members of Rho GTPase family is often found associated with many disease states, targeting of Rho GTPases and related signaling pathways for potential therapeutic benefits has been extensively pursued. Recent progress in this field of studies by peptide and peptidomemic inhibitors has provided important validations to this principle.

Protection of lithium metal surfaces using chlorosilanes.

In this paper, we present a new approach for protecting metallic lithium surfaces based on a reaction between the thin native layer of lithium hydroxide present on the surface and various chlorosilane derivatives. The chemical composition of the resulting layer and the chemistry involved in layer formation were analyzed by polarization modulated infrared reflection absorption spectroscopy (PM-IRRAS), X-ray photoelectron spectroscopy (XPS), and energy dispersive X-ray analysis (EDX). Spectroscopy shows the disappearance of surface hydroxide groups and the appearance of silicon and chloride on the lithium surface.

Using light to induce energy and electron transfer or molecular motions in multicomponent systems.

Light-induced processes are at the basis of fundamental natural phenomena as well as of a variety of applications. Since the functions that can arise from the interaction between light and matter depend on the degree of complexity and organization of the receiving 'matter', the research on these processes has progressively moved from molecular to supramolecular (multicomponent) systems, thereby originating the field of supramolecular photochemistry. In this context, examples of photochemical molecular devices and machines--that is, multicomponent chemical systems capable to perform specific functions under light stimulation--have been developed.

Synthesis of an end-capped sexithiophene bearing fused tetrathiafulvalene (TTF) units.

[structure: see text] We report the synthesis of a novel end-capped sexithiophene derivative bearing two pendent, fused tetrathiafulvalene (TTF) units linked to the main chain through 1,4-dithiin heterocycles. Cyclic voltammetry and absorption spectroscopy are used to investigate the electronic properties of this hybrid electroactive material. The oligomer has a band gap of 2.

Cyclohexenylphenyldiazene: a simple surrogate of the azobenzene photochromic unit.

We have carried out an experimental and computational study on the ground- and excited-state photochemical and photophysical properties of (1-cyclohexenyl)phenyldiazene (CPD), a species formally derived from azobenzene in which one of the phenyl rings is replaced by a 1-cyclohexene substituent. The results show that CPD does substantially behave like azobenzene, but with a higher (approximately 70%) Phi(Z-->E) (npi*) photoisomerization quantum yield, calling for CPD as an effective alternative of azobenzene itself with new functionalization possibilities. By use of state-of-the-art ab initio CASPT2//CASSCF minimum energy path computations, we have identified the most efficient decay and isomerization routes of the absorbing singlet (pipi*), S1 (npi*), T1, and S0 states of CPD.

A low band gap conjugated polymer for supercapacitor devices.

We present the electrochemical polymerization and characterization of a stable and dopable polyindophenine derivative starting from monomer 5. The fabrication of supercapacitor devices was carried out by direct electrochemical polymerization on an ITO-coated slide. Furthermore, the galvanostatic and potentiostatic experiments conducted on these supercapacitors have shown that the polyindophenine-derivative material has very good cyclability, over a potential range of 1.

Photoinduced energy- and electron-transfer processes in dinuclear Ru(II)-Os(II), Ru(II)-Os(III), and Ru(III)-Os(II) trisbipyridine complexes containing a shape-persistent macrocyclic spacer.

The PF6- salt of the dinuclear [(bpy)2Ru(1)Os(bpy)2]4+ complex, where 1 is a phenylacetylene macrocycle which incorporates two 2,2'-bipyridine (bpy) chelating units in opposite sites of its shape-persistent structure, was prepared. In acetonitrile solution, the Ru- and Os-based units display their characteristic absorption spectra and electrochemical properties as in the parent homodinuclear compounds. The luminescence spectrum, however, shows that the emission band of the Ru(II) unit is almost completely quenched with concomitant sensitization of the emission of the Os(II) unit.

Synthesis and supramolecular properties of molecular clips with anthracene sidewalls.

Novel molecular clips with anthracene sidewalls (1 a-c) were synthesized; they form stable host-guest complexes with a variety of electron-deficient aromatic and quinoid molecules. According to single-crystal structure analyses of clip 1 c and 1,2,4,5-tetracyanobenzene (TCNB) complex 14@1 b, the clips' anthracene sidewalls have to be compressed substantially during the complex formation to provide attractive pi-pi interactions between the aromatic guest molecule and the two anthracene sidewalls in the complex. The compression and expansion of aromatic sidewalls are calculated by molecular mechanics to be low-energy processes, so the energy required for compression of the anthracene sidewalls during complex formation is apparently overcompensated by the gain in energy resulting from the attractive pi-pi interactions.

Complete charge pooling is prevented in viologen-based dendrimers by self-protection.

We have investigated the electrochemical behavior, and chemical and photosensitized reduction of two dendrimers based on a 1,3,5-trisubstituted benzenoid core, which contain 9 and 21 4,4'-bipyridinium (usually called viologen) units, respectively, in their branches and are terminated with tetraarylmethane groups. For comparison purposes, the behavior of reference compounds that contain a single viologen unit have also been investigated. We have found that only part of the viologen units can be reduced in the dendrimer species.

Controllable donor-acceptor neutral [2]rotaxanes.

In pursuit of a neutral bistable [2]rotaxane made up of two tetraarylmethane stoppers--both carrying one isopropyl and two tert-butyl groups located at the para positions on each of three of the four aryl rings--known to permit the slippage of the pi-electron-donating 1,5-dinaphtho[38]crown-10 (1/5DNP38C10) at the thermodynamic instigation of pi-electron-accepting recognition sites, in this case, pyromellitic diimide (PmI) and 1,4,5,8-naphthalenetetracarboxylate diimide (NpI) units separated from each other along the rod section of the rotaxane's dumbbell component, and from the para positions of the fourth aryl group of the two stoppers by pentamethylene chains, a modular approach was employed in the synthesis of the dumbbell-shaped compound NpPmD, as well as of its two degenerate counterparts, one (PmPmD) which contains two PmI units and the other (NpNpD) which contains two NpI units. The bistable [2]rotaxane NpPmR, as well as its two degenerate analogues PmPmR and NpNpR, were obtained from the corresponding dumbbell-shaped compounds NpPmD, PmPmD, and NpNpD and 1/5DNP38C10 by slippage. Dynamic 1H NMR spectroscopy in CD2Cl2 revealed that shuttling of the 1/5DNP38C10 ring occurs in NpNpR and PmPmR, with activation barriers of 277 K of 14.

Polyvalent scaffolds. Counting the number of seats available for eosin guest molecules in viologen-based host dendrimers.

We have prepared and investigated two dendrimers based on a 1,3,5-trisubstituted benzenoid-type core, containing 9 and 21 viologen units in their branches, respectively, and terminated with tetraarylmethane derivatives. We have shown that, in dichloromethane solution, such highly charged cationic species give rise to strong host-guest complexes with the dianionic form of the red dye eosin. Upon complexation, the absorption spectrum of eosin becomes broader and is slightly displaced toward lower energies, whereas the strong fluorescence of eosin is completely quenched.