Jhindan Mukherjee

Wet chemical functionalization of III-V semiconductor surfaces: alkylation of gallium phosphide using a Grignard reaction sequence.

Single-crystalline gallium phosphide (GaP) surfaces have been functionalized with alkyl groups via a sequential Cl-activation, Grignard reaction process. X-ray photoelectron (XP) spectra of freshly etched GaP(111)A surfaces demonstrated reproducible signals for surficial Cl after treatment with PCl(5) in chlorobenzene. The measured Cl content consistently corresponded to approximately a monolayer of coverage on GaP(111)A. In contrast, GaP(111)B surfaces treated with the same PCl(5) solution under the same conditions exhibited macroscale roughening and yielded XP spectra that showed irreproducible Cl surface content often below the limit of detection of the spectrometer. The Cl-activated GaP(111)A surfaces were reactive toward alkyl Grignard reagents. Sessile contact angle measurements between water and GaP(111)A after various levels of treatment showed that GaP(111)A surfaces became significantly more hydrophobic following reaction with either CH(3)MgCl or C(18)H(37)MgCl. GaP(111)A surfaces reacted with C(18)H(37)MgCl demonstrated wetting properties consistent with surfaces modified with a dense layer of long alkyl chains. High-resolution C 1s XP spectra indicated that the carbonaceous species at GaP(111)A surfaces treated with Grignard reagents could not be ascribed solely to adventitious carbon. A shoulder in the C 1s XP spectra occurred at slightly lower binding energies for these samples, commensurate with the formation of Ga-C bonds. High-resolution P 2p XP spectra taken at various times during prolonged direct exposure to ambient laboratory air indicated that the resistance of GaP(111)A to surface oxidation was greatly enhanced after surface modification with alkyl groups. GaP(111)A samples that had been functionalized with C(18)H(37)- groups exhibited less than 0.1 nm of surface oxide after 7 weeks of continuous exposure to ambient air. GaP(111)A surfaces terminated with C(18)H(37)- groups were also used as platforms in Schottky heterojunctions with Hg. In comparison to freshly etched GaP(111)A, the alkyl-terminated GaP(111)A samples yielded current-voltage responses that were in accord with metal-insulator-semiconductor devices and indicated that this reaction strategy could be used to alter rates of heterogeneous charge transfer controllably. The wet chemical surface functionalization strategy described herein does not involve thiol/sulfide chemistry or gas-phase pretreatments and represents a new synthetic methodology for controlling the interfacial properties of GaP and related Ga-based III-V semiconductors.

Wet Chemical Functionalization of III–V Semiconductor Surfaces: Alkylation of Gallium Arsenide and Gallium Nitride by a Grignard Reaction Sequence

Crystalline gallium arsenide (GaAs) (111)A and gallium nitride (GaN) (0001) surfaces have been functionalized with alkyl groups via a sequential wet chemical chlorine activation, Grignard reaction process. For GaAs(111)A, etching in HCl in diethyl ether effected both oxide removal and surface-bound Cl. X-ray photoelectron (XP) spectra demonstrated selective surface chlorination after exposure to 2 M HCl in diethyl ether for freshly etched GaAs(111)A but not GaAs(111)B surfaces. GaN(0001) surfaces exposed to PCl(5) in chlorobenzene showed reproducible XP spectroscopic evidence for Cl-termination. The Cl-activated GaAs(111)A and GaN(0001) surfaces were both reactive toward alkyl Grignard reagents, with pronounced decreases in detectable Cl signal as measured by XP spectroscopy. Sessile contact angle measurements between water and GaAs(111)A interfaces after various levels of treatment showed that GaAs(111)A surfaces became significantly more hydrophobic following reaction with C(n)H(2n-1)MgCl (n = 1, 2, 4, 8, 14, 18). High-resolution As 3d XP spectra taken at various times during prolonged direct exposure to ambient lab air indicated that the resistance of GaAs(111)A to surface oxidation was greatly enhanced after reaction with Grignard reagents. GaAs(111)A surfaces terminated with C(18)H(37) groups were also used in Schottky heterojunctions with Hg. These heterojunctions exhibited better stability over repeated cycling than heterojunctions based on GaAs(111)A modified with C(18)H(37)S groups. Raman spectra were separately collected that suggested electronic passivation by surficial Ga-C bonds at GaAs(111)A. Specifically, GaAs(111)A surfaces reacted with alkyl Grignard reagents exhibited Raman signatures comparable to those of samples treated with 10% Na(2)S in tert-butanol. For GaN(0001), high-resolution C 1s spectra exhibited the characteristic low binding energy shoulder demonstrative of surface Ga-C bonds following reaction with CH(3)MgCl. In addition, 4-fluorophenyl groups were attached and detected after reaction with C(6)H(4)FMgBr, further confirming the susceptibility of Cl-terminated GaN(0001) to surface alkylation. However, the measured hydrophobicities of alkyl-terminated GaAs(111)A and GaN(0001) were markedly distinct, indicating differences in the resultant surface layers. The results presented here, in conjunction with previous studies on GaP, show that atop Ga atoms at these crystallographically related surfaces can be deliberately functionalized and protected through Ga-C surface bonds that do not involve thiol/sulfide chemistry or gas-phase pretreatments.

Modular Integration of Upconverting Nanocrystal–Dendrimer Composites for Folate Receptor‐Specific NIR Imaging and Light‐Triggered Drug Release

Upconversion nanocrystals (UCNs) display near-infrared (NIR)-responsive photoluminescent properties for NIR imaging and drug delivery. The development of effective strategies for UCN integration with other complementary nanostructures for targeting and drug conjugation is highly desirable. This study reports on a core/shell-based theranostic system designed by UCN integration with a folate (FA)-conjugated dendrimer for tumor targeting and with photocaged doxorubicin as a cytotoxic agent. Two types of UCNs (NaYF4:Yb/Er (or Yb/Tm); diameter = ≈50 to 54 nm) are described, each displaying distinct emission properties upon NIR (980 nm) excitation. The UCNs are surface modified through covalent attachment of photocaged doxorubicin (ONB-Dox) and a multivalent FA-conjugated polyamidoamine (PAMAM) dendrimer G5(FA)6 to prepare UCN@(ONB-Dox)(G5FA). Surface plasmon resonance experiments performed with G5(FA)6 dendrimer alone show nanomolar binding avidity (KD = 5.9 × 10(-9) M) to the folate binding protein. This dendrimer binding corresponds with selective binding and uptake of UCN@(ONB-Dox)(G5FA) by FAR-positive KB carcinoma cells in vitro. Furthermore, UCN@(ONB-Dox)(G5FA) treatment of FAR(+) KB cells inhibits cell growth in a light dependent manner. These results validate the utility of modularly integrated UCN-dendrimer nanocomposites for cell type specific NIR imaging and light-controlled drug release, thus serving as a new theranostic system.

Physicochemical and Electrochemical Properties of Etched GaP(111)A and GaP(111)B Surfaces

The observable chemical, electrochemical, and morphological features of GaP(111) surfaces after wet chemical etching have been assessed using X-ray photoelectron spectroscopy, atomic force microscopy, and electrochemical impedance spectroscopy. HF(aq), NH4F(aq), H2SO4(aq), HCl(aq), HCl-HNO3(aq), and dilute Br-2 in CH3OH (with and without a follow-up alkaline etch) are all potent etchants for GaP(111) but yield distinctly different GaP(111)A and GaP(111)B surface conditions. Freshly etched GaP(111)B interfaces show higher residual oxide coverages and are generally rougher than similarly treated GaP(111)A surfaces. Differential capacitance measurements of n-GaP(111)A and n-GaP(111)B electrodes show that various etchants result in a wide range of apparent values for the conduction bandedge potentials, spanning approximately 700 mV in acetonitrile. These data show that these etched surfaces are not equivalent and that the observable physicochemical and electrochemical properties of GaP(111) are strongly influenced by the choice of wet chemical etchant. Additionally, X-ray photoelectron spectra show that adsorption of (4-fluorophenyl)methanethiol onto GaP(111) is insensitive to surface orientation or etching method, indicating no dominant covalent interaction between organic thiols and GaP(111) interfaces.

A lipopolysaccharide binding heteromultivalent dendrimer nanoplatform for Gram negative cell targeting

We report on the practicality of a heteromultivalent design strategy for a nanoplatform that targets lipopolysaccharide molecules (LPS) present on the surface of Gram-negative bacteria. This design is based on the conjugation of a poly(amido amine) (PAMAM) dendrimer with two types of ligands, each having distinct affinities: (i) polymyxin B (PMB) as a primary high affinity ligand; (ii) a PMB-mimicking dendritic branch as an auxiliary low affinity ligand. Co-conjugation of these two ligands maximizes the efficiency of the primary ligand even when the primary ligand is present at a low valency on the nanoplatform (mean nPMB≈ 1). By performing surface plasmon resonance studies using a LPS-immobilized cell wall model, we identified an ethanolamine (EA)-terminated branch as the auxiliary ligand that promotes binding avidity via heteromultivalent association. PMB conjugation of the dendrimer with excess EA branches led to LPS avidity two orders of magnitude greater than unconjugated PMB. Such tight binding observed by SPR corresponded well with adsorption to E. coli cells and with potent bactericidal activity in vitro.

Control of an Unusual Photo-Claisen Rearrangement in Coumarin Caged Tamoxifen through an Extended Spacer

The use of coumarin caged molecules has been well documented in numerous photocaging applications including for the spatiotemporal control of Cre-estrogen receptor (Cre-ERT2) recombinase activity. In this article, we report that 4-hydroxytamoxifen (4OHT) caged with coumarin via a conventional ether linkage led to an unexpected photo-Claisen rearrangement which significantly competed with the release of free 4OHT. The basis for this unwanted reaction appears to be related to the coumarin structure and its radical-based mechanism of uncaging, as it did not occur in ortho-nitrobenzyl (ONB) caged 4OHT that was otherwise linked in the same manner. In an effort to perform design optimization, we introduced a self-immolative linker longer than the ether linkage and identified an optimal linker which allowed rapid 4OHT release by both single-photon and two-photon absorption mechanisms. The ability of this construct to actively control Cre-ERT2 mediated gene modifications was investigated in mouse embryonic fibroblasts (MEFs) in which the expression of a green fluorescent protein (GFP) reporter dependent gene recombination was controlled by 4OHT release and measured by confocal fluorescence microscopy and flow cytometry. In summary, we report the implications of this photo-Claisen rearrangement in coumarin caged compounds and demonstrate a rational linker strategy for addressing this unwanted side reaction.

A Thioacetal Photocage Designed for Dual Release: Application in the Quantitation of Therapeutic Release by Synchronous Reporter Decaging

Despite the immense potential of existing photocaging technology, its application is limited by the paucity of advanced caging tools. Here, we report on the design of a novel thioacetal ortho‐nitrobenzaldehyde (TNB) dual arm photocage that enabled control of the simultaneous release of two payloads linked to a single TNB unit. By using this cage, which was prepared in a single step from commercial 6‐nitroverataldehyde, three drug–fluorophore conjugates were synthesized: Taxol‐TNB‐fluorescein, Taxol‐TNB‐coumarin, and doxorubicin‐TNB‐coumarin, and long‐wavelength UVA light‐triggered release experiments demonstrated that dual payload release occurred with rapid decay kinetics for each conjugate. In cell‐based assays performed in vitro, dual release could also be controlled by UV exposure, resulting in increased cellular fluorescence and cytotoxicity with potency equal to that of unmodified drug towards the KB carcinoma cell line. The extent of such dual release was quantifiable by reporter fluorescence measured in situ and was found to correlate with the extent of cytotoxicity. Thus, this novel dual arm cage strategy provides a valuable tool that enables both active control and real‐time monitoring of drug activation at the delivery site.

Mechanism of Cooperativity and Nonlinear Release Kinetics in Multivalent Dendrimer–Atropine Complexes

Despite extensive studies on drug delivery using multivalent complexation systems, the biophysical basis for release kinetics remains poorly defined. The present study addresses this aspect involved in the complexation of a fifth generation poly(amidoamine) (PAMAM) dendrimer with atropine, an essential antidote used for treating organophosphate poisoning. First, we designed (1)H NMR titration studies for determining the molecular basis of the drug complexation with a glutarate-modified anionic dendrimer. These provide evidence pointing to a combination of electrostatic and hydrophobic interactions as the driving forces for dendrimer complexation with the alkaloid drug molecule. Second, using LC-MS/MS spectrometry, we determined the dissociation constants (KD) at steady state and also measured the drug release kinetics of atropine complexes with four negatively charged dendrimer types. Each of these dendrimers has a high payload capacity for up to ∼ 100 atropine molecules. However, the affinity of the atropine to the carrier was highly dependent on the drug to dendrimer ratio. Thus, a complex made at a lower loading ratio (≤ 0.1) displayed greater atropine affinity (KD ≈ μM) than other complexes prepared at higher ratios (>10), which showed only mM affinity. This negative cooperative variation in affinity is tightly associated with the nonlinear release kinetics observed for each complex in which drug release occurs more slowly at the later time phase at a lower loading ratio. In summary, the present study provides novel insights on the cooperativity as the mechanistic basis for nonlinear release kinetics observed in multivalent carrier systems.