British Relations with Tanjore (1748-1799).

The thesis examines the policy followed by the British towards Tanjore from the beginning of the Carnatic Wars to the end of the century. They came into close contact with that state during the course of the first Carnatic War and found her alliance and co-operation invaluable in establishing their power in India. By the end of the century, when their power was supreme, they found it convenient to annex Tanjore into their dominions. Throughout this period, Tanjore had not engaged herself in any hostilities towards the British; on the contrary, she had remained a faithful ally and to a great extent a protected power. But the fact that she was considered a tributary of the Nawab of Arcot, who in turn was dependent upon the British for his existence, reduced her to the position of discharging the demands of both the British and the Nawab; and suffer the consequences of heavy payments, which she could ill-afford. With the increase in the Nawab's dependence and their superiority, the British came to control the affairs of tooth the Nawato and the Raja. Since Arcot was of greater importance and the Nawato considered a particular ally, the interests of Tanjore were sacrificed to the dictates of his avarice and Tanjore itself was left under his complete control for a few years. When restored eventually to the Raja, the British found it opportune to establish their authority in Tanjore, reducing the Raja to complete dependence upon them. Their primary concern was the subsidy Tanjore paid for the protection she received from them. The treaties concluded in 1787, 1792 and 1799 were all in theory voluntary agreements between two independent states; tout on each occasion, the British move was only to safeguard and secure the punctual payment of that subsidy. When Tanjore found herself incapable of shouldering this heavy responsibility, the British found it necessary to annex the territory, leaving the Raja with a pension

Reaction of lactim ethers and lactim sulfides with electrophiles: attackat nitrogen followed by ring-opening under neutral conditions

Electrophilic push-pull molecules react at the nitrogen of lactim ethers and lactim sulfides; subsequent hydrolysis gives ring-opened products in good yields

Conversion of carbonimidodithioates to carbamates

Carbonimidodithioates derived from primary amines or α-amino acid esters have been converted to N-benzyloxycarbonyl derivatives under mild conditions by treatment first with sodium benzyl alcoholate and then with water. N-Benzyloxycarbonyl α-amino acids have been generated from the methyl esters by alkaline hydrolysis or from the allyl esters by Pd0-catalysed de-allylation

Synthesis and metal complexation of chiral 3-mono-or 3, 3-bis-allyl-2-hydroxypyrrolopyrazine-1, 4-diones

A novel synthesis of chiral cyclic hydroxamic acids (4, 6, 8 and 10) related to cyclodipeptides is described. The crucial reduction of the nitro group of the N-nitroacetyl derivatives of (S)-α-amino acid esters is brought about by zinc-aq. ammonium chloride. The FeIII and CuII complexes of one such cyclic hydroxamic acid 10a have been prepared and their DNAse activity investigated

Folding of a donor–acceptor polyrotaxane by using noncovalent bonding interactions

Mechanically interlocked compounds, such as bistable catenanes and bistable rotaxanes, have been used to bring about actuation in nanoelectromechanical systems (NEMS) and molecular electronic devices (MEDs). The elaboration of the structural features of such rotaxanes into macromolecular materials might allow the utilization of molecular motion to impact their bulk properties. We report here the synthesis and characterization of polymers that contain π electron-donating 1,5-dioxynaphthalene (DNP) units encircled by cyclobis(paraquat-p-phenylene) (CBPQT4+), a π electron-accepting tetracationic cyclophane, synthesized by using the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The polyrotaxanes adopt a well defined “folded” secondary structure by virtue of the judicious design of two DNP-containing monomers with different binding affinities for CBPQT4+. This efficient approach to the preparation of polyrotaxanes, taken alongside the initial investigations of their chemical properties, sets the stage for the preparation of a previously undescribed class of macromolecular architectures

Tissue-Specific Gene Delivery via Nanoparticle Coating

Author Manuscript: 2010 August 1.The use of biomaterials for gene delivery can potentially avoid many of the safety concerns with viral gene delivery. However, the efficacy of polymeric gene delivery methods is low, particularly in vivo. One significant concern is that the interior and exterior composition of polymeric gene delivery nanoparticles are often coupled, with a single polymer backbone governing all functions from biophysical properties of the polymer/DNA particle to DNA condensation and release. In this work we develop electrostatically adsorbed poly(glutamic acid)-based peptide coatings to alter the exterior composition of a core gene delivery particle and thereby affect tissue-specificity of gene delivery function in vivo. We find that with all coating formulations tested, the coatings reduce potential toxicity associated with uncoated cationic gene delivery nanoparticles following systemic injection. Particles coated with a low 2.5:1 peptide:DNA weight ratio (w/w) form large 2 μ sized particles in the presence of serum that can facilitate specific gene delivery to the liver. The same particles coated at a higher 20:1 w/w form small 200 nm particles in the presence of serum that can facilitate specific gene delivery to the spleen and bone marrow. Thus, variations in nanoparticle peptide coating density can alter the tissue-specificity of gene delivery in vivo.National Institutes of Health (U.S.) (BRP: 1R01CA124427-01)National Institutes of Health (U.S.) (EB 000244)National Institutes of Health (U.S.) (U54 CA119349-01)David & Lucile Packard Foundation (Fellowship 1999-1453A

Development of Degradable, pH‐Sensitive Star Vectors for Enhancing the Cytoplasmic Delivery of Nucleic Acids

The report describes the synthesis of degradable, pH‐sensitive, membrane‐destabilizing, star‐shaped polymers where copolymers of hydrophobic hexyl methacrylate (HMA) and 2‐(dimethylamino)ethyl methacrylate (DMAEMA) monomers are grafted from the secondary face of a beta‐cyclodextrin (β‐CD) core via acid‐labile hydrazone linkages using atom transfer radical polymerization. The effect of the graft's molecular weight, HMA/DMAEMA molar ratio, and the fraction of DMAEMA converted to cationic N,N,N‐trimethylaminoethyl methacrylate (TMAEMA) monomers on polymer's transfection capacity is systematically investigated. Results show that all star‐shaped polymers condense anti‐GAPDH silencing RNA (siRNA) into nanosized particles at +/‐ ratio ≤ 4:1. Star polymers with shorter (25kDa) P(HMA‐ co ‐DMAEMA‐ co ‐TMAEMA) grafts are more efficient and less cytotoxic than carriers with longer (40kDa) grafts. The results show that increasing the ratio of hydrophobic HMA monomers in graft's composition higher than 50 mole% dramatically reduces polymer's aqueous solubility and abolishes their transfection capacity. Further, retention of DMAEMA monomers in graft's composition provide a buffering capacity that enhanced the endosomal escape and transfection capacity of the polymers. These systematic studies show that β‐CD‐P(HMA‐ co ‐DMAEMA‐ co ‐TMAEMA) 4.8 polymer with a 25 kDa average graft's molecular weight and a 50/25/25 ratio of HMA/DMAEMA/TMAEMA monomers is the most efficient carrier in delivering the siRNA cargo into the cytoplasm of epithelial cancer cells. A series of degradable, pH‐sensitive, membrane‐destabilizing, star‐shaped polymers is synthesized. Star polymers are engineered to “sense” the drop in endosomal pH, which triggers the hydrolysis of acid‐labile hydrazone linkages and release of membrane‐active grafts that rupture the endosomal membrane and release the loaded siRNA cargo into the cytoplasm to produce the desired knockdown of targeted gene expression at both the mRNA and protein levels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99666/1/3885_ftp.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99666/2/adfm_201203762_sm_suppl.pd

Synthesis of β‐Cyclodextrin Containing Copolymer via “Click” Chemistry and Its Self‐Assembly in the Presence of Guest Compounds

We report the synthesis of a hydrophilic copolymer with one polyethylene glycol (PEG) block and one β‐cyclodextrin (β‐CD) containing block by a “click” reaction between azido‐substituted β‐CD and propargyl flanking copolymer. 1 H NMR study suggested a highly efficient conjugation of β‐CD units by this approach. The obtained copolymer was used as a host macromolecule to construct assemblies in the presence of hydrophobic guests. For assemblies containing a hydrophobic polymer, their size can be simply adjusted by simply changing the content of hydrophobic component. By serving as a guest molecule, hydrophobic drugs can also be loaded accompanying the formation of nanoparticles, and the drug payload is releasable. Therefore, the copolymer synthesized herein can be employed as a carrier for drug delivery. The synthesis of β‐cyclodextrin containing block copolymer via a “click” reaction is reported. The self‐assembly of this newly synthesized copolymer in the presence of guest compounds can lead to the formation of core–shell structured nanoparticles. These assemblies can be employed as novel delivery vehicles for therapeutics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91173/1/marc_201100814_sm_suppl.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/91173/2/664_ftp.pd