Sudershan R. Gondi

Folate-Conjugated Thermoresponsive Block Copolymers: Highly Efficient Conjugation and Solution Self-Assembly

A combination of controlled radical polymerization and azide-alkyne click chemistry was employed to prepare temperature-responsive block copolymer micelles conjugated with biological ligands with potential for active targeting of cancer tissues. Block copolymers of N-isopropylacrylamide (NIPAM) and N,N-dimethylacrylamide (DMA) were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization with an azido chain transfer agent (CTA). Pseudo-first-order kinetics and linear molecular weight dependence on conversion were observed for the RAFT polymerizations. CuI-catalyzed coupling with propargyl folate resulted in folic acid residues being efficiently conjugated to the alpha-azido chain ends of the homo and block copolymers. Temperature-induced self-assembly resulted in aggregates capable of controlled release of a model hydrophobic drug. CuI-catalyzed azide-alkyne cycloaddition has proven superior to conventional methods for conjugation of biological ligands to macromolecules, and the general strategy presented herein can potentially be extended to the preparation of folate-functionalized assemblies with other stimuli susceptibility (e.g., pH) for therapeutic and imaging applications.

Hyperbranched Polymers via RAFT Copolymerization of an Acryloyl Trithiocarbonate

Hyperbranched copolymers of N-isopropylacrylamide (NIPAM) and styrene were prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization in the presence of a novel acryloyl trithiocarbonate, namely 1-[3-(2-methyl-2-dodecylsulfanylthiocarbonylsulfanylpropionyloxy)propyl]-1H-[1,2,3]triazol-4-ylmethyl acrylate. By employing an example of ‘click chemistry’, we were able to prepare the vinyl RAFT chain transfer agent (CTA) by copper-catalyzed 1,3-dipolar cycloaddition of an azido-functionalized trithiocarbonate and propargyl acrylate. The resulting CTA facilitated the preparation of highly branched poly(N-isopropylacrylamide) (PNIPAM) and polystyrene. Interestingly, the branched PNIPAM demonstrated a reduced lower critical solution temperature (LCST) of 25°C as opposed to the conventional value of 32°C expected for linear PNIPAM, an effect attributed to increased contribution of hydrophobic dodecyl trithiocarbonate end groups.

Synthesis of N,N′‐bis(2‐Thiazolinyl)‐, N,N′‐bis(2‐Thiazolyl)‐, and N,N′‐bis(2‐Pyrimidinyl)‐Benzene Dicarboxamides

Abstract New heteroaromatic benzene dicarboxamides have been synthesized in moderate to good yields by the reactions of 2‐aminothiazoline, 2‐aminothiazole, and 2‐aminopyrimidine with phthaloyl dichloride, isophthaloyl dichloride, and terephthaloyl dichloride in the presence of an organic base. The amides are sparingly soluble in common organic solvents but dissolve readily in dimethyl sulfoxide. Reactions of 2‐aminothiazoline and 2‐aminopyrimidine with phthaloyl dichloride yield a tricyclic compound and an imide, respectively, instead of the expected products.

Mono-, bis-, and tris-1,3-dithiolane aromatic derivatives by esterification and amidation reactions

We report the synthesis of new aromatic derivatives containing the 1,3-dithiolane moiety. The 1,3-dithiolane groups are attached by simple esterification or amidation reactions of 1,3-dithiolane-2-carbonyl chloride with hydroxybenzenes, aniline, or 2,6-diaminopyridine. The isolated yields of these compounds range from 40 to 87%. All of the reported compounds are white solids and stable to air and moisture.

Easy and Rapid Method for Disulfide Syntheses Using Nanophase-Manganese (VII) Oxide Coated Clay

Disulfide bond formation by the oxidation of several thiol compounds using nanophase manganese (VII) oxide coated clay (NM7O coated clay) in chlorinated, nonchlorinated (toluene), and polar solvents (water) is described. During the process, nitro and methoxy groups remain unaffected. The NM7O coated clay is easily prepared, stable, and inexpensive to manufacture. Furthermore, this and other studies prove that NM7O coated clay properties, i.e., mineralogy, chemical, and reactivity, are different from KMnO4. This rapid and facile synthesis coupled with the use of the recyclable NM7O coated clay catalyst will save energy due to low temperature and rapid reaction times, as well as minimal disposal problems, thus decreasing production costs.

Synthesis of (Hetaryl)alkylamines from the Reactions of 2‐Aminopyrimidine, 2‐Aminothiazole, and 2‐Aminothiazoline with Benzyl Bromide and Xylylene Dibromides

Abstract Alkylation reactions of 2‐aminopyrimidine, 2‐aminothiazole, 2‐aminothiazoline, and their Cbz‐protected derivatives are described. Reactions with benzyl bromide proceed to give monoalkylated products with 2‐aminopyrimidine and 2‐aminothiazole, but 2‐aminothiazoline gives a dialkylated product. Reactions with xylylene dibromides are complicated by the tendency to form intramolecularly cyclized products with the ortho‐dibromide and insoluble products with the meta‐ and para‐dibromides.

Cholane derivatives with potential ligating groups at the 3- and 24-positions

Abstract Starting from readily available lithocholic acid, a number of new cholane derivatives have been prepared consisting of the same or different electron‐donor groups at the 3‐ and 24‐positions. Yields ranged from good to excellent. The donor groups were chosen on the basis of their known ability to coordinate to transition‐metal ions and include pyridyl, 1,3‐dithiolanyl, phenylthioether, and oxime ether groups.

Metallopolymer formation from the interaction of a hydrolyzed dithiolane-carboxylate ligand with Ag(I)

On reaction with Ag(I), phenyl 1,3-dithiolane-2-carboxylate undergoes hydrolysis and assembles into a metal–organic coordination polymer. Crystals of the polymer were characterized by X-ray crystallography. The metallopolymer exists as a sheet-like structure consisting of twisted strands. An additional structural feature is an apparent Ag–Ag interaction (3.0679 Å) supported by the thiolane sulfur atoms. Carboxyl and triflate oxygen atoms are also key donors to the Ag(I) centers.