Ashok K. Kakkar

Miktoarm star polymers: advances in synthesis, self-assembly, and applications

Miktoarm polymers are a relatively new and unique class of macromolecules, and constitute a topical area of research due to their intriguing properties which can be tailored by varying their polymer arms. Much emphasis has been placed in the recent past in developing synthetic methodologies to these star polymers, and examining their self-assembly in solution. This review summarizes the progress made in the area of miktoarm star polymers in terms of their synthesis, behavior in solution, and applications. The different synthetic strategies to construct a variety of miktoarm star polymers are described, and each methodology strikes a balance between ease of synthesis and control over the final architecture. The self-assembly of miktoarm polymers in solution is then elaborated, which is frequently studied as a function of either arm-length (an intrinsic property of the star) or the application of an external stimulus (pH, temperature, etc.). This is followed by an overview of the applications of these stars in areas including drug delivery.

Di-, tri-, pseudo-di- and pseudo-tetra-acetylenic polymers of platinum: Synthesis, characterization and optical spectra

Abstract Reactions of Me 3 Sn-CC-(CC-) m -CC-SnMe 3 ( m = 0, 1) ( 1 , 2 ), Me 3 Sn-(CC) m - p -C 6 H 4 -(CC) m -SnMe 3 ( m = 1, 2) ( 3 , 4 ) with the platinum metal halide complexes, [Pt(X n Bu 3 ) 2 Cl 2 ] (where X = P ( 5 ), As ( 6 )) afford high molecular weight polymeric species, [-Pt(X n Bu 3 ) 2 -CC-(CC) m -CC-] n ( 7-10 ), and [-Pt(P n Bu 3 ) 2 -(CC) m - p -C 6 H 4 -(CC) m -] n ( 11, 12 ) in excellent yields. Investigations of the optical absorption and photoluminescence spectra of these complexes show extended π-electron conjugation through the metal sites on the chain, with a lower π-π* energy gap for triacetylenic than for the diacetylenic polymeric complexes. Well-resolved vibronic structure associated with the -CC- stretching frequency is observed for both absorption and emission, indicating strong electron-phonon coupling for the di- and triacetylenic polymers.

Synthesis of monomeric, oligomeric and polymeric σ-acetylide complexes of platinum, palladium, nickel and rhodium

Abstract Reaction of equimolar quantities of Me3SnCCRCCSnMe3 [R = p-C6H4; p-C6H2(CH3)2; p-C6H4-p-C6H4] with the group 10 metal dihalide complexes, [M(XnBU3)2Cl2] (M = Pt, Pd, Ni; X = P, As; Bu = butyl) affords the polymeric species trans-[−M(XnBU3)2(-CCRCC-)]n in excellent yields. By varying the stoichiometry of these reactions, complexes of the type trans-[M(XnBU3)2(−CCRCCSnMe3)2] and trans-[ClM(XnBU3)2CCRCCM(Xn BU3)2Cl], which are precursors to higher oligomers, can be prepared. Treatment of the former with an excess of trans-[M(XnBU3)2Cl2] affords the trimetallic compound trans-[ClM(XnBU3)2(−CCRCC−)M(XnBU3)2(−CCRCC−)M(XnBU3)2Cl], while reaction of the latter with two equivalents of Me3SnCCRCCSnMe3 followed by two equivalents of trans-[M(XnBu3)2Cl2] gives the complex trans-[ClM(XnBU3)2(−CCRCC−)M(XnBu3)2(−CCRCC−)M(XnBu3)2(−CCRCC−)M(XnBu3)2Cl]. Treatment of the complex [Rh(PPhl)3Cl] (Ph = Phenyl) with one equivalent of Me3SnCCRCCSnMe3 [R = p-C6H4-p-C6H4] gives the polymeric species [−Rh(PPh3)2(SnMe3)(−CCRCC−)]n. Model compounds for other rhodium-containing σ-acetylide complexes have been obtained from the reaction between the complex [Rh(PMe3)4Cl] (Me = CH3) and Me3SnCCC6H5 which yields the compound mer,trans-[Rh(PMe3)3-(SnMe3)(−CCC6H5)2] via the intermediate [Rh(PMe3)4(−CH5]. Reaction of [Rh(PMe3)4Cl] with one equivalent of Me3SnCCRCCSnMe3 [R = p-C6H4-p-C6H4] yields the polymer mer,trans[−Rh(PMe3)3(SnMe3)(−CCRCC−)]n.

Synthesis and optical spectroscopy of linear long-chain di-terminal alkynes and their Pt–σ-acetylide polymeric complexes

A variety of straight-chain alkynes with extended π-conjugation through benzene, anthracene and thiophene linker units in the backbone, H—CC—R′—CC—R—CC—R′—CC—H (R =p-C6H4, 9,10-C14H8, 2,5-C4H2S; R′=p-C6H4, p-C6H4-C6H4-p) has been synthesized. The alkynyl chromophores with an anthracene spacer unit are highly emissive in solution with luminescence quantum yields of up to 0.5. The platinum σ-acetylide polymeric complexes of the above ligands show strong absorptions associated with metal-to-alkynyl ligand charge transfer (MLCT) transitions. It is clear that the π-conjugation is maintained through the metal centres and the optical gap for the polymer, [graphic omitted]Pt(PBun3)2-CC-p-C6H4-CC-9,10-C14H8-CC-p-C6H4-CC[graphic omitted]n is lower than for the complexes [graphic omitted]Pt(PBn3)2-CC-R′-CC-R-CC-R′-CC[graphic omitted]n(R =p-C6H4, 2,5-C4H2S; R′=p-C6H4; p-C6H4-C6H4-p).

Rigid rod σ-acetylide complexes of iron, ruthenium and osmium

Abstract The synthetic utility of bis(trimethylstannyl)alkynyls in the preparation of Group 8 metal (Fe 2+ , Ru 2+ , Os 2+ ) σ-acetylide monomeric, M(DEPE) 2 (CCC 6 H 5 ) 2 (M  Fe 2+ , Ru 2+ ; DEPE = 1,2-bis(diethylphosphino)ethane), Ru(DPPE) 2 (CCC 6 H 5 ) 2 (DPPE = 1,2-bis(diphenylphosphino)ethane), Os(DPPM) 2 (CCC 6 H 5 ) 2 (DPPM = 1,2-bis(diphenylphosphino)methane) and polymeric, [M(DEPE) 2 CCRCC] n (M  Fe 2+ , Ru 2+ ), [Os(DPPM) 2 CCRCC-] n (R = p -C 6 H 4 - C 6 H 4 - p , p -C 6 H 4 , p -C 6 H 2 (CH 3 ) 2 ) complexes is demonstrated. The linear arrangement of the acetylenic units around octahedral metal centres is confirmed by a single crystal X-ray structure determination of the model complex trans -[Ru(DPPE) 2 (CCC 6 H 5 ) 2 ].

Design and Evaluation of Multifunctional Nanocarriers for Selective Delivery of Coenzyme Q10 to Mitochondria

Impairments of mitochondrial functions have been associated with failure of cellular functions in different tissues, leading to various pathologies. We report here a mitochondria-targeted nanodelivery system for coenzyme Q10 (CoQ10) that can reach mitochondria and deliver CoQ10 in adequate quantities. Multifunctional nanocarriers based on ABC miktoarm polymers (A = poly(ethylene glycol (PEG), B = polycaprolactone (PCL), and C = triphenylphosphonium bromide (TPPBr)) were synthesized using a combination of click chemistry with ring-opening polymerization, self-assembled into nanosized micelles, and were employed for CoQ10 loading. Drug loading capacity (60 wt %), micelle size (25-60 nm), and stability were determined using a variety of techniques. The micelles had a small critical association concentration and were colloidally stable in solution for more than 3 months. The extraordinarily high CoQ10 loading capacity in the micelles is attributed to good compatibility between CoQ10 and PCL, as indicated by the low Flory-Huggins interaction parameter. Confocal microscopy studies of the fluorescently labeled polymer analog together with the mitochondria-specific vital dye label indicated that the carrier did indeed reach mitochondria. The high CoQ10 loading efficiency allowed testing of micelles within a broad concentration range and provided evidence for CoQ10 effectiveness in two different experimental paradigms: oxidative stress and inflammation. Combined results from chemical, analytical, and biological experiments suggest that the new miktoarm-based carrier provides a suitable means of CoQ10 delivery to mitochondria without loss of drug effectiveness. The versatility of the click chemistry used to prepare this new mitochondria-targeting nanocarrier offers a widely applicable, simple, and easily reproducible procedure to deliver drugs to mitochondria or other intracellular organelles.

Gold: a versatile tool for in vivo imaging

Imaging for diagnostics or for evaluating the efficacy of a particular drug constitutes a key challenge, and a topical area of research in nanomedicine. There has been a tremendous effort devoted to the evaluation of a variety of contrast agents, and gold nanomaterials due to their inherent and geometrically induced optical properties, have offered significant potential for in vivo imaging. The gold based nanostructures that are most commonly employed for biological imaging include nano-spheres, -rods, -shells, -cages and -stars. This feature article provides an overview of the current state of research in utilizing these gold nano-architectures in imaging, with particular emphasis on modalities such as two-photon luminescence, computed tomography, optical coherence tomography, near infrared and photoacoustic imaging.

Superparamagnetic iron oxide based nanoprobes for imaging and theranostics

The need to target, deliver and subsequently evaluate the efficacy of therapeutics in the treatment of a disease has provided added impetus in developing novel and highly efficient contrast agents. Superparamagnetic iron oxide nanoparticles (SPIONs) have offered tremendous potential in designing advanced magnetic resonance imaging (MRI) diagnostic agents, due to their unique physicochemical properties. There has been tremendous effort devoted in the recent past in developing synthetic methodologies through which their size, hydrodynamic radii, chemical composition and morphologies could be tailored at the nanoscale. This enables one to fine tune their magnetic behavior, and thus their MRI response. While novel synthetic strategies are being assembled for directing SPIONs to the diseased site as well as imparting them stealth and biocompatibility, it is also essential to evaluate their biological toxicological profiles. This review highlights recent advances that have been made in the synthesis of SPIONs, subsequent functionalization with desired entities, and a discussion on their use as MRI contrast agents in cardiovascular research.

Synthesis and optical spectroscopy of platinum-metal-containing di- and tri-acetylenic polymers

Optical absorption and photoluminescence measurements on the title polymers, [graphic omitted]Pt(PBu3n)2—(CC)m—CC[graphic omitted]n(m= 1, 2) show that there is appreciable π-electron conjugation extending through the metal sites on the chain, with a lower π–π* energy gap for the triacetylenic than for the diacetylenic compound.

Alkyne-Azide “Click” Chemistry in Designing Nanocarriers for Applications in Biology

The alkyne-azide cycloaddition, popularly known as the “click” reaction, has been extensively exploited in molecule/macromolecule build-up, and has offered tremendous potential in the design of nanomaterials for applications in a diverse range of disciplines, including biology. Some advantageous characteristics of this coupling include high efficiency, and adaptability to the environment in which the desired covalent linking of the alkyne and azide terminated moieties needs to be carried out. The efficient delivery of active pharmaceutical agents to specific organelles, employing nanocarriers developed through the use of “click” chemistry, constitutes a continuing topical area of research. In this review, we highlight important contributions click chemistry has made in the design of macromolecule-based nanomaterials for therapeutic intervention in mitochondria and lipid droplets.