Narsimha Mamidi

Alkyl cinnamates as regulator for the C1 domain of protein kinase C isoforms.

The protein kinase C (PKC) family of serine/threonine kinases is an attractive drug target for the treatment of cancer and other diseases. Natural product curcumin is known to interact with PKC isoforms through the C1 domain and modulate PKC activity. The reported results demonstrate that the symmetric curcumin molecule might act as two separate units during its recognition of C1 domains. To understand the importance of the two halves of curcumin in PKC binding and to develop effective PKC regulators, we synthesized a series of alkyl cinnamates (1-8), characterized absorption and fluorescence properties and measured binding affinities with the C1b subdomains of PKC isoforms. The binding parameters of the monomeric compounds and liposomes containing compounds confirmed their interaction with the C1b subdomains of PKCδ and PKCθ. The molecular docking analysis with PKCδ and PKCθ C1b subdomains revealed that the alkyl cinnamates form hydrogen bond with the backbone of the protein at the same binding site as that of diacylglycerol and phorbol esters. The results show that the alkyl cinnamates bind to the activator binding site of PKCs and both methoxy and hydroxyl groups play important roles in the binding process.

Zn(OTf) 2 ‑Promoted Chemoselective Esterification of Hydroxyl Group Bearing Carboxylic Acids

Selective esterification of aliphatic and aromatic carboxylic acids with various alcohols is studied using triphenylphosphine, I2, and a catalytic amount of Zn(OTf)2. Use of this catalyst allows the formation of esters at a faster rate with good to excellent yield by activating the in situ generated acyloxyphosphonium ion intermediate. During the esterification process, both their aromatic and aliphatic hydroxyl groups are fully preserved from transesterification. The results show that the bulkiness and the reactivity of this doubly activated intermediate III control the selectivity and the rate of the reaction, respectively. The method is also useful for direct amidation reactions.

Effects of ortho substituent groups of protocatechualdehyde derivatives on binding to the C1 domain of novel protein kinase C.

Diacylglycerol (DAG) regulates a broad range of cellular functions including tumor promotion, apoptosis, differentiation, and growth. Thus, the DAG-responsive C1 domain of protein kinase C (PKC) isoenzymes is considered to be an attractive drug target for the treatment of cancer and other diseases. To develop effective PKC regulators, we conveniently synthesized (hydroxymethyl)phenyl ester analogues targeted to the DAG binding site within the C1 domain. Biophysical studies and molecular docking analysis showed that the hydroxymethyl group, hydrophobic side chains, and acyl group at the ortho position are essential for their interactions with the C1-domain backbone. Modifications of these groups showed diminished binding to the C1 domain. The active (hydroxymethyl)phenyl ester analogues showed more than 5-fold stronger binding affinity for the C1 domain than DAG. Therefore, our findings reveal that (hydroxymethyl)phenyl ester analogues represent an attractive group of C1-domain ligands that can be further structurally modified to improve their binding and activity.

Design, development, EUVL applications and nano mechanical properties of a new HfO2 based hybrid non-chemically amplified resist

A new HfO2 based hybrid polymer HfO2–methacrylate–MAPDST (HMM, Mw ∼27885 g mol−1) was synthesized by reacting the hybrid monomer HfO2–methacrylate (HM) with (methacryloyloxy)phenyldimethylsulfoniumtriflate (MAPDST) in the presence of azobisisobutyronitrile (AIBN) as a radical initiator in tetrahydrofuran and acetonitrile (2:1; v/v) at 60 °C for Extreme Ultraviolet Lithography (EUVL) applications as a non-chemically amplified resist (n-CAR) material. Transmission Electron Microscope (TEM) and Dynamic Light Scattering (DLS) analyses revealed the particle sizes of HM and HMM hybrids as ∼3–5 nm and ∼12 nm respectively. Thin films of thickness ∼53 nm were prepared by spin coating 3% (w/v) solutions of HMM in methanol onto 4′′ p-type Si wafers consisting of a 40 nm hexamethyldisilazane (HMDS) under layer. The films were then subjected to EUV exposure at a dose of 51.7127 mJ cm−2 on a micro exposure tool (MET) with an Advanced Light Source (ALS) at SEMATECH Berkeley using standard mask IMO228775 with field R4C3 (LBNL low flare bright-field). The EUV E0 dose used for the exposure was 22 mJ cm−2. Field Emission Scanning Electron Microscope (FE-SEM) micrographs of the EUV exposed hybrid resist films showed isolated line patterns of 80, 70, 60, 50, 45, 40, 35 and 30 nm for 5:1 duty cycle, of which 80 to 50 nm line patterns were well resolved, whereas patterns of 45 to 30 nm or higher resolutions exhibited undesirable traits like bridging, fracturing, de-adhesion, peel-off and pattern collapse. To comprehend the reasons behind these undesirable traits, nano-mechanical properties (modulus and adhesion) of the EUV exposed and developed resist patterns were investigated by using Peak Force-Quantitative Nano-Mechanical (PF-QNM) tapping mode Atomic Force Microscope (AFM). These studies revealed ∼18% and ∼19% reductions in Derjaguin–Muller–Toporov (DMT) modulus and adhesion magnitudes respectively with an increase in isolated line pattern resolution from 80 to 30 nm for 5:1 duty cycles. The reduction in modulus and adhesion magnitudes might have caused the observed fracturing, peel-off and collapse of the high resolution line patterns during the pattern development processes.

Aromatic Sulfonium Polyoxomolybdates: Solid‐State Photochromic Materials with Tunable Properties

A new aromatic sulfonium counter-ion motif for polyoxometalate (POM) clusters with potential for structural and electronic fine-tuning has been designed. Its two derivatives 4-hydroxyphenyl dimethylsulfonium triflate (HPDST) and 4-(allyloxy)phenyl dimethylsulfonium triflate (APDST) exhibit ionic liquid behaviors under ambient conditions. HPDST and APDST are used to develop a series of aromatic sulfonium POM hybrids (HPDS/APDS)n[XMo12 O40] (HPDS and APDS are the cations of HPDST and APDST, respectively; X=P or Si; n=3 or 4), which are tested for photochromic behavior. On exposure to UV light, these POM hybrids undergo color change from yellow to green/blue. The coloration kinetics half lives (t1/2) are less for APDS-based hybrids than for HPDS-based hybrids, suggesting that alkyl substitution on the phenolic group helps to fine-tune the electron availability on the sulfonium moiety and hence to control the photochromic behavior of the POM hybrids. The t1/2 values of these hybrids are considerably lower than those of the reported aliphatic sulfonium POM hybrids. We have also demonstrated the application of photoreduced POM hybrids as catalysts for the reduction of 4-nitrophenol to 4-aminophenol.

Physicochemical characterization of diacyltetrol-based lipids consisting of both diacylglycerol and phospholipid headgroups

We describe the synthesis of diacyltetrol-based hybrid lipids in which one of the hydroxymethyl groups is modified with an anionic phospholipid headgroup. The hybrid lipids form a monolayer at the air–water interface. In aqueous solution, these lipids form stable liposomes that exhibit a negative surface potential across a wide pH range. The liposomes aggregate in the presence of Ca2+ ions and release encapsulated cationic reporter rhodamine 6G (R6G) at a faster rate than anionic reporter carboxyfluorescein (CF). The hybrid lipids strongly interact with the C1b subdomain of the protein kinase C (PKC)-θ isoform. These new lipids structurally mimic diacylglycerol and conventional phospholipids, and provide an opportunity to explore their physicochemical properties.

An organic–inorganic hybrid supramolecular framework material based on a [P2W18O62]6− cluster and Yb & Na complexes of pyridine-2,6-dicarboxylic acid: a catalyst for selective oxidation of sulfides in water with H2O2

A rare-earth-containing polyoxometalate (RECP) hybrid, {(Yb (PDCH2)2(PDCH))·Na(H2O)2·(Na(PDCH)(H2O)2)}2[P2W18O62]·14H2O (1), based on [P2W18O62]6− cluster anions and cationic Yb & Na complex units of pyridine-2,6-dicarboxylic acid (PDCH2) has been synthesized under normal reaction conditions, which exhibited a supramolecular 3-D framework structure in the crystal lattice. Hybrid 1 acts as a green catalyst for the selective oxidation of sulfides in water with H2O2 as the reagent.

Cytotoxicity evaluation of unfunctionalized multiwall carbon nanotubes-ultrahigh molecular weight polyethylene nanocomposites

The carbon nanotubes were chosen for this study since long, small to medium diameter, and unfunctionalized nanotubes are considered less favorable for nontoxic applications. The intent of the study is to expand the use of CNTs beyond current understood nontoxic means. Multiwall carbon nanotube/ultrahigh molecular weight polyethylene (MWCNT/UHMWPE) nanocomposites were prepared by reinforcing long chain UHMWPE with MWCNTs. These nanocomposites were prepared to study their cytotoxicity assessments with human fibroblast cell lines. Cell adhesion, proliferation, and differentiation were studied with human fibroblast cell lines. In vitro studies revealed good cell viability on the surface of MWCNT/UHMWPE composites even after 72 h. The nanocomposites showed better cell attachment for fibroblasts than pristine UHMWPE. Overall, the results showed that MWCNT/UHMWPE composites displayed good cellular growth and biocompatibility indicating another way CNTs can be nontoxic. These nanocomposites offer nontoxic conditions that can be used in biomedical devices because the long chain UHMWPE is entangled with long MWCNTs.