Synthesis and Physicochemical Characterization of New C‐Functionalized Derivatives of the Gadolinium(III) Complex with 3,6,10‐Tris(carboxymethyl)‐3,6,10‐triazadodecanedioic Acid (H5ttda) Exhibiting Fast Water Exchange – Potential Paramagnetic Reporters for Molecular Imaging

To confirm the observation that [Gd(ttda)] derivatives have a significantly shorter residence time τ_M of the coordinated H₂O molecule than [Gd(dtpa)], four new C‐functionalized [Gd(ttda)] complexes, [Gd(4‐Me‐ttda)] ( 1 ), [Gd(4‐Ph‐ttda)] ( 2 ), [Gd(9‐Me‐ttda)] ( 3 ), and [Gd(9‐Ph‐ttda)] ( 4 ), were prepared and characterized (H₅ttda=3,6,10‐tris(carboxymethyl)‐3,6,10‐triazadodecanedioic acid; H₅dtpa=3,6,9‐tris(carboxymethyl)‐3,6,9‐triazaundecanedioic acid). The temperature dependence of the proton relaxivity for these complexes at 0.47 T and of the ¹⁷O transverse relaxation rate of H₂¹⁷O at 7.05 T confirm that the proton relaxivity is not limited by the H₂O‐exchange rate. The residence time of the H₂O molecules in the first coordination sphere of the gadolinium complexes at 310 K, as calculated from ¹⁷O‐NMR data, is 13, 43, 2.9, and 56 ns for 1, 2, 3 , and 4 , respectively. At 310 K, the longitudinal relaxivity of 2 is higher than for the parent compound [Gd(ttda)] and the other complexes of the series. The stability of the new compounds was studied by transmetallation with Zn²⁺ ions. All the new complexes are more stable than the parent compound [Gd(ttda)].     

Plant-Derived Stilbenoids as DNA-Binding Agents: From Monomers to Dimers

Stilbenoids are natural compounds endowed with several biological activities, including cardioprotection and cancer prevention. Among them, (±)-trans-δ-viniferin, deriving from trans-resveratrol dimerization, was investigated in its ability to target DNA duplex and G-quadruplex structures by exploiting NMR spectroscopy, circular dichroism, fluorescence spectroscopy and molecular docking. (±)-trans-δ-Viniferin proved to bind both the minor and major grooves of duplexes, whereas it bound the 3’- and 5’-ends of a G-quadruplex by stacking on the outer quartets, accompanied by rearrangement of flanking residues. Specifically, (±)-trans-δ-viniferin demonstrated higher affinity for the investigated DNA targets than its monomeric counterpart. Additionally, the methoxylated derivatives of (±)-trans-δ-viniferin and trans-resveratrol, i. e. (±)-pterostilbene-trans-dihydrodimer and trans-pterostilbene, respectively, were evaluated, revealing similar binding modes, affinities and stoichiometries with the DNA targets as their parent analogues. All tested compounds were cytotoxic at μM concentration on several cancer cell lines, showing DNA damaging activity consistent with their ability to tightly interact with duplex and G-quadruplex structures.     

A tripodal ruthenium-gadolinium metallostar as a potential α(v)β(3) integrin specific bimodal imaging contrast agent

Gd(III)-containing metallostar contrast agents are gaining increased attention, because their architecture allows for a slower tumbling rate, which, in turn, results in larger relaxivities. So far, these metallostars find possible applications as blood pool contrast agents. In this work, the first example of a tissue-selective metallostar contrast agent is described. This RGD-peptide decorated Ru(II)(Gd(III))(3)metallostar is synthesized as an α(v)β(3)-integrin specific contrast agent, with possible applications in the detection of atherosclerotic plaques and tumor angiogenesis. The contrast agent showed a relaxivity of 9.65 s(-1) mM(-1), which represents an increase of 170%, compared to a low-molecular-weight analogue, because of a decreased tumbling rate (τ(R) = 470 ps). The presence of the MLCT band (absorption 375-500 nm, emission 525-850 nm) of the central Ru(II)(Ph-Phen)(3)-based complex grants the metallostar attractive luminescent properties. The (3)MLCT emission is characterized by a quantum yield of 4.69% and a lifetime of 804 ns, which makes it an interesting candidate for time-gated luminescence imaging. The potential application as a selective MRI contrast agent for α(v)β(3)-integrin expressing tissues is shown by an in vitro relaxometric analysis, as well as an in vitroT(1)-weighted MR image.     

Tetranuclear d-f Metallostars: Synthesis, Relaxometric, and Luminescent Properties

A novel ditopic ligand DTPA-ph-phen, based on 1,10-phenanthroline and diethylenetriaminepentaacetic acid (DTPA) units, has been designed and fully characterized by (1)H, (13)C, and 2D-COSY NMR spectroscopy, IR and electrospray ionization mass spectrometry (ESI-MS) techniques. The DTPA core of the ligand specifically binds Ln(III) ions (Ln = Eu, Gd) resulting in formation of the [Ln{DTPA-ph-phen}(H(2)O)](-) complex. The photophysical properties of the Eu(III) compound have been investigated, and the complex shows characteristic red luminescence with an overall quantum yield of 2.2%. Reaction of [Gd{DTPA-ph-phen}(H(2)O)](-) with Ru(II) leads to further self-assembly into a heterobimetallic metallostar complex containing Gd(III) and Ru(II) in a 3:1 ratio. This tetranuclear [(Gd{DTPA-ph-phen})(3)(H(2)O)(3)Ru](-) complex (Gd(3)Ru), formed by the coordination of Ru(II) to the 1,10-phenanthroline unit, has been characterized by a range of experimental techniques and evaluated toward its feasibility as a potential bimodal optical/MRI agent. The Gd(3)Ru metallostar shows intense metal-to-ligand charge transfer (MLCT) transition resulting in intense light absorption in the visible spectral region. Upon irradiation into this MLCT band at 450 nm, the Gd(3)Ru complex exhibits red broad-band luminescence in the range of 550-800 nm centered at 610 nm with a quantum yield of 4.8%. Proton nuclear magnetic relaxation dispersion (NMRD) measurements indicate that the Gd(3)Ru complex exhibits an enhanced relaxivity value r(1) of 36.0 s(-1) mM(-1) per metallostar molecule at 20 MHz and 310 K. The ability of the complex to noncovalently bind to human serum albumin (HSA) was investigated, but no significant interaction was detected.     

Ramp-Up-Phase Current-Profile Control of Tokamak Plasmas via Nonlinear Programming

The achievement of suitable toroidal-current-density profiles in tokamak plasmas plays an important role in enabling high fusion gain and noninductive sustainment of the plasma current for steady-state operation with improved magnetohydrodynamic stability. The evolution in time of the current profile is related to the evolution of the poloidal magnetic flux, which is modeled in normalized cylindrical coordinates using a partial differential equation (PDE) usually referred to as the magnetic flux diffusion equation. The dynamics of the plasma current density profile can be modified by the total plasma current and the power of the noninductive current drive. These two actuators, which are constrained not only in value and rate but also in their initial and final values, are used to drive the current profile as close as possible to a desired target profile at a specific final time. To solve this constrained finite-time open-loop PDE optimal control problem, model reduction based on proper orthogonal decomposition is combined with sequential quadratic programming in an iterative fashion. The use of a low-dimensional dynamical model dramatically reduces the computational effort and, therefore, the time required to solve the optimization problem, which is critical for a potential implementation of a real-time receding-horizon control strategy.      

Diode-pumped regenerative amplifier delivering 100-mJ single-mode laser pulses

We report on a side-pumped Nd:phosphate laser regenerative amplifier that delivers laser pulses of as much as 100 mJ in a single TEM mode. The laser beam is mode matched to the amplification medium by an intracavity fused-silica phase plate for mode shaping and a telescope for adjustment of the beam mode to the amplification rod section such that most of the energy stored in the rod is transferred to the laser pulses. As a result of the good overlap and the low loss, an optical-to-optical conversion efficiency of as much as 10% was measured for a pumping current of 80 A and greater than 100-mJ output pulses.