Roberto R. Gil

Monoplatinum Doping of Gold Nanoclusters and Catalytic Application

We report single-atom doping of gold nanoclusters (NCs), and its drastic effects on the optical, electronic, and catalytic properties, using the 25-atom system as a model. In our synthetic approach, a mixture of Pt(1)Au(24)(SC(2)H(4)Ph)(18) and Au(25)(SC(2)H(4)Ph)(18) was produced via a size-focusing process, and then Pt(1)Au(24)(SC(2)H(4)Ph)(18) NCs were obtained by selective decomposition of Au(25)(SC(2)H(4)Ph)(18) in the mixture with concentrated H(2)O(2) followed by purification via size-exclusion chromatography. Experimental and theoretical analyses confirmed that Pt(1)Au(24)(SC(2)H(4)Ph)(18) possesses a Pt-centered icosahedral core capped by six Au(2)(SC(2)H(4)Ph)(3) staples. The Pt(1)Au(24)(SC(2)H(4)Ph)(18) cluster exhibits greatly enhanced stability and catalytic activity relative to Au(25)(SC(2)H(4)Ph)(18) but a smaller energy gap (E(g) ≈ 0.8 eV vs 1.3 eV for the homogold cluster).

Probing the Structure and Charge State of Glutathione-Capped Au25(SG)18 Clusters by NMR and Mass Spectrometry

Despite the recent crystallographic determination of the crystal structure of Au(25)(SCH(2)CH(2)Ph)(18) clusters, the question--whether all thiolate-capped, 25-atom gold clusters adopt the same structure, regardless of the types of thiols (e.g., long-chain alkylthiols, aromatic thiols, or other functionalized ones)--still remains unanswered. To crystallize long-chain or bulky ligand (e.g., glutathione)-capped Au(25)(SR)(18) clusters has proven to be difficult due to the major amorphousness caused by such ligands; therefore, one needs to seek other strategies to probe the structural information of such gold clusters. Herein, we report a strategy to probe the Au(25) core structure and surface thiolate ligand distribution by means of NMR in combination with mass spectrometry. We use glutathione-capped Au(25)(SG)(18) clusters as an example to demonstrate the utility of this strategy. One-dimensional (1D) and two-dimensional (2D) correlation NMR spectroscopic investigation of Au(25)(SG)(18) reveals fine spectral features that explicitly indicate two types of surface binding modes of thiolates, which is consistent with the ligand distribution in the Au(25)(SCH(2)CH(2)Ph)(18) cluster. Laser desorption ionization (LDI) mass spectrometry analysis shows that Au(25)(SG)(18) exhibits an identical ionization and core fragmentation pattern with phenylethylthiolate-capped Au(25) clusters. The charge state of the native Au(25)(SG)(18) clusters was determined to be -1 by comparing their optical spectrum with those of [Au(25)(SCH(2)CH(2)Ph)(18)](q) of different charge states (q = -1, 0). Taken together, our results led to the conclusion that glutathione-capped Au(25)(SG)(18) clusters indeed adopt the same structure as that of Au(25)(SCH(2)CH(2)Ph)(18). This conclusion is also valid for other types of thiolate-capped Au(25) clusters, including hexyl- and dodecylthiolates. Interestingly, the chiral optical responses (e.g., circular dichroism (CD) signals in the visible wavelength region) from the Au(25)(SG)(18) clusters seem to be imparted by the chiral glutathione ligands because no similar CD signals were observed in Au(25)(SCH(2)CH(2)Ph)(18).

Crystal Structure of Barrel-Shaped Chiral Au130(p-MBT)50 Nanocluster.

We report the structure determination of a large gold nanocluster formulated as Au130(p-MBT)50, where p-MBT is 4-methylbenzenethiolate. The nanocluster is constructed in a four-shell manner, with 55 gold atoms assembled into a two-shell Ino decahedron. The surface is protected exclusively by -S-Au-S- staple motifs, which self-organize into five ripple-like stripes on the surface of the barrel-shaped Au105 kernel. The Au130(p-MBT)50 can be viewed as an elongated version of the Au102(SR)44. Comparison of the Au130(p-MBT)50 structure with the recently discovered icosahedral Au133(p-TBBT)52 nanocluster (where p-TBBT = 4-tert-butylbenzenethiolate) reveals an interesting phenomenon that a subtle ligand effect in the para-position of benzenethiolate can significantly affect the gold atom packing structure, i.e. from the 5-fold twinned Au55 decahedron to 20-fold twinned Au55 icosahedron.

Constitutional, Configurational, and Conformational Analysis of Small Organic Molecules on the Basis of NMR Residual Dipolar Couplings

NMR spectroscopy is arguably one of the most powerful tools available to chemists for the structural analysis of molecules. NMR experiments based on the nuclear Overhauser enhancement (NOE) and on the analysis of J coupling constants have been used intensively in the configurational and conformational analysis of small organic molecules. However, as these two NMR parameters provide only localized structural information, they fail to provide information on the relative configuration of remotely located molecular fragments. Unlike NOEs and J coupling constants, the direct spin– spin interaction known as dipolar coupling (Dij ; Figure 1) can provide very powerful structural information of a nonlocal character. The value of Dij between two nuclei i and j (which can either be bonded to one another or not directly connected) depends not only on the distance between them (r), but also on the angle of the internuclear vector (rij) with respect to the direction of the magnetic field (B0), which acts as a global axis of reference. Hence, from the equation in Figure 1, it can be inferred that a unique combination of dipolar-coupled pairs of spins can produce a unique set of dipolar couplings, which in turn can enable unambiguous determination of the relative spatial arrangement of atoms in a molecule. This spatial arrangement reflects the constitution, configuration, and preferred conformation of the molecule. When the concept is explained in this way, the use of dipolar couplings for the analysis of small molecules sounds very simple and straightforward. However, the size of dipolar couplings is on the order of kilohertz. In solid-state powders, all possible spatial orientations adopted by molecules lead to extremely broad lines in the NMR spectrum, which makes the extraction of individual dipolar couplings impossible. In solution, dipolar couplings average out as a result of isotropic molecular tumbling and are not observable in the NMR spectrum (isotropic conditions). However, if molecules are forced to adopt a minor degree of alignment in solution, a measurable fraction of the original dipolar coupling, known as residual dipolar coupling (RDC), is observed in the NMR spectrum. RDCs conserve the same structural information provided by the original dipolar couplings, since they are scaled down proportionally. From a practical standpoint, RDCs can be measured relatively easily provided that the degree of alignment is weak (0.01–0.1 % of the maximum dipolar-coupling value). If the alignment is too strong, the RDCs produced are very difficult to analyze. In theory, any sufficiently proximate pair of magnetically active nuclei will yield a RDC value; however, one-bond C–H RDCs (DCH) and two-bond H–H RDCs (DHH) are relatively easy to measure and are commonly used in the structural analysis of small molecules. The first small molecule to be aligned was benzene in 1963; however, its alignment in organic liquid crystals was so strong that RDCs were difficult to analyze. RDCs have been used extensively in the analysis of biomacromolecules since 1997. 5] The first application of RDCs to the configurational analysis of small organic molecules was proposed almost simultaneously by Mangoni et al. and Yan et al. in 2003, although their methods were restricted to the use of water-compatible alignment media. Soon afterwards, the development of alignment media compatible with organic solvents began with the introduction of lyotropic liquidcrystalline phases formed by homopolypeptides dissolved in Figure 1. Dependence of the dipolar coupling (Dij) of a pair of magnetically active nuclei i and j (bonded or nonbonded) on the internuclear distance (r) and on the angle (V) of the internuclear vector (rij) and the direction of the magnetic field (B0). In the equation, m0 is the permeability of a vacuum, g is the gyromagnetic constant, and h is the Planck constant; the brackets around the angular term represent averaging in solution.

Functional assessment of human dendritic cells labeled for in vivo 19F magnetic resonance imaging cell tracking

BACKGROUND AIMS Dendritic cells (DC) are increasingly being used as cellular vaccines to treat cancer and infectious diseases. While there have been some promising results in early clinical trials using DC-based vaccines, the inability to visualize non-invasively the location, migration and fate of cells once adoptively transferred into patients is often cited as a limiting factor in the advancement of these therapies. A novel perflouropolyether (PFPE) tracer agent was used to label human DC ex vivo for the purpose of tracking the cells in vivo by (19)F magnetic resonance imaging (MRI). We provide an assessment of this technology and examine its impact on the health and function of the DC. METHODS Monocyte-derived DC were labeled with PFPE and then assessed. Cell viability was determined by examining cell membrane integrity and mitochondrial lipid content. Immunostaining and flow cytometry were used to measure surface antigen expression of DC maturation markers. Functional tests included bioassays for interleukin (IL)-12p70 production, T-cell stimulatory function and chemotaxis. MRI efficacy was demonstrated by inoculation of PFPE-labeled human DC into NOD-SCID mice. RESULTS DC were effectively labeled with PFPE without significant impact on cell viability, phenotype or function. The PFPE-labeled DC were clearly detected in vivo by (19)F MRI, with mature DC being shown to migrate selectively towards draining lymph node regions within 18 h. CONCLUSIONS This study is the first application of PFPE cell labeling and MRI cell tracking using human immunotherapeutic cells. These techniques may have significant potential for tracking therapeutic cells in future clinical trials.

Chirality in Gold Nanoclusters Probed by NMR Spectroscopy

We report the analysis of chirality in atomically precise gold nanoclusters by nuclear magnetic resonance (NMR) spectroscopic probing of the surface ligands. The Au(38)(SR)(24) and Au(25)(SR)(18) (where, R = CH(2)CH(2)Ph) are used as representative models for chiral and nonchiral nanoclusters, respectively. Interestingly, different (1)H signals for the two germinal protons in each CH(2) of the ligands on the chiral Au(38)(SR)(24) nanocluster were observed, so-called diastereotopicity. For α-CH(2) (closest to the chiral metal core), a chemical shift difference of up to ~0.8 ppm was observed. As for the nonchiral Au(25)(SCH(2)CH(2)Ph)(18)(-)TOA(+) nanocluster, no diastereotopicity was detected (i.e., no chemical shift difference for the two protons in the CH(2)), confirming the Au(25) core being nonchiral. These two typical examples demonstrate that NMR spectroscopy can be a useful tool for investigating chirality in Au nanoclusters. Since the diastereotopicity induced on the methylene protons by chiral nanoclusters is independent of the enantiomeric composition of the chiral particles, NMR can probe the chirality of the nanoclusters even in the case of a racemic mixture, while circular dichroism spectroscopy is not useful for racemic mixtures.

End-group effects on the properties of PEG-co-PGA hydrogels

A series of resorbable poly(ethylene glycol)-co-poly(glycolic acid) (PEG-co-PGA, 4KG5) macromonomers have been synthesized with the chemistries from three different photopolymerizable end-groups (acrylates, methacrylates and urethane methacrylates). The aim of the study is to examine the effects of the chemistry of the cross-linker group on the properties of photocross-linked hydrogels. 4KG5 hydrogels were prepared by photopolymerization with high vinyl group conversion as confirmed by (1)H nuclear magnetic resonance spectrometry using a 1D diffusion-ordered spectrometry pulse sequence. Our study reveals that the nature of end-groups in a moderately amphiphilic polymer can adjust the distribution and size of the micellar configuration in water, leading to changes in the macroscopic structure of hydrogels. By varying the chemistry of the cross-linker group (diacrylates (DA), dimethacrylates (DM) and urethane dimethacrylates (UDM)), we determined that the hydrophobicity of a single core polymer consisting of poly(glycolic acid) could be fine-tuned, leading to significant variations in the mechanical, swelling and degradation properties of the gels. In addition, the effects of cross-linker chemistry on cytotoxicity and proliferation were examined. Cytotoxicity assays showed that the three types of hydrogels (4KG5 DA, DM and UDM) were biocompatible and the introduction of RGD ligand enhanced cell adhesion. However, differences in gel properties and stability differentially affected the spreading and proliferation of myoblast C2C12 cells.

Structural Discrimination in Small Molecules by Accurate Measurement of Long‐Range Proton–Carbon NMR Residual Dipolar Couplings

Accurate measurement of long-range CH residual dipolar couplings (RDCs) (2DCH and 3DCH) by a new selective J-scaled HSQC experiment significantly improves the structural discrimination power of RDCs in small molecules with multiple stereocenters. The extraction of the long-range couplings is clean and straightforward, and in most cases yields the sign of the RDC too. The experiment is demonstrated with 10-epi-8-deoxycumambrin B, a tricyclic natural compound with five chiral centers.

Tri-icosahedral Gold Nanocluster [Au37(PPh3)10(SC2H4Ph)10X2](+): Linear Assembly of Icosahedral Building Blocks.

The [Au37(PPh3)10(SR)10X2](+) nanocluster (where SR = thiolate and X = Cl/Br) was theoretically predicted in 2007, but since then, there has been no experimental success in the synthesis and structure determination. Herein, we report a kinetically controlled, selective synthesis of [Au37(PPh3)10(SC2H4Ph)10X2](+) (counterion: Cl(-) or Br(-)) with its crystal structure characterized by X-ray crystallography. This nanocluster shows a rod-like structure assembled from three icosahedral Au13 units in a linear fashion, consistent with the earlier prediction. The optical absorption and the electrochemical and catalytic properties are investigated. The successful synthesis of this new nanocluster allows us to gain insight into the size, structure, and property evolution of gold nanoclusters that are based upon the assembly of icosahedral units (i.e., cluster of clusters). Some interesting trends are identified in the evolution from the monoicosahedral [Au13(PPh3)10X2](3+) to the bi-icosahedral [Au25(PPh3)10(SC2H4Ph)5X2](2+) and to the tri-icosahedral [Au37(PPh3)10(SC2H4Ph)10X2](+) nanocluster, which also points to the possibility of achieving even longer rod nanoclusters based upon assembly of icosahedral building blocks.

Alkaloids in Bufonid Toads (Melanophryniscus): Temporal and Geographic Determinants for Two Argentinian Species

Bufonid toads of the genus Melanophryniscus represent one of several lineages of anurans with the ability to sequester alkaloids from dietary arthropods for chemical defense. The alkaloid profile for Melanophryniscus stelzneri from a location in the province of Córdoba, Argentina, changed significantly over a 10-year period, probably indicating changes in availability of alkaloid-containing arthropods. A total of 29 alkaloids were identified in two collections of this population. Eight alkaloids were identified in M. stelzneri from another location in the province of Córdoba. The alkaloid profiles of Melanophryniscus rubriventris collected from four locations in the provinces of Salta and Jujuy, Argentina, contained 44 compounds and differed considerably between locations. Furthermore, alkaloid profiles of M. stelzneri and M. rubriventris strongly differed, probably reflecting differences in the ecosystem and hence in availability of alkaloid-containing arthropods.