| dc.description.abstract | Dendrimers are a class of perfectly branched symmetric monodisperse macromolecules, which are synthesized using a stepwise procedure. Due to their highly symmetric structure, they possess a definite core, discrete generations and a large number of terminal units. The large number of terminal units and its compact globular conformation endow this class of macromolecules with several unique properties. Over the past two decades, a number of researchers have synthesized a variety of dendrimers and explored their potential applications in various fields ranging from drug delivery, energy harvesting to catalysis. However, dendrimers require tedious stepwise synthesis and purification which limits their scalability. Hyperbranched polymers (HBPs) are a related class of macromolecules having similar highly branched structure but with large number of linear defects and, therefore, they may be considered as unsymmetrical analogues of dendrimers. Despite of having a large number of defects, HBPs display majority of the properties which dendrimers possess such as, high solubility, low chain entanglement, low solution and melt viscosity, encapsulation of guest molecules, conformational adaptability etc. The origin of these defects lies in the single-step statistical random growth process. Although, hyperbranched polymers possess a randomly branched structure, they also carry a large number of peripheral units, like dendrimers. Since, hyperbranched polymers are prepared in a single step, they can be readily scaled up which make them commercially attractive. One of the most widely used methods to prepare hyperbranched polymers is by polycondensation of a AB2 monomer.
In our laboratory, during past decade a novel melt trans-etherification methodology was developed to prepare hyperbranched polyethers. For this method, a AB2 monomer was designed having two methoxy benzyl units and one aliphatic hydroxyl group, which in presence of a mild organic acid at 150°C undergoes melt polymerization under continuous removal of methanol. Although, this method allows one to prepare a variety of high molecular weight hyperbranched polyethers structures, it suffers from one serious limitation associated with the monomer structure; the aromatic ring in the monomer should be either electronically deactivated or per-substituted to preclude a side reaction due to electrophilic aromatic substitution, which could result in the formation of insoluble cross-linked product.
Polyacetals are a class of polymers which readily degrades under mildly acidic conditions. One of the primary objectives of this thesis was to develop a simple strategy to prepare hyperbranched polyacetal, which would be a new class of highly branched acid-labile scaffold. To achieve this, we used a relatively under-explored chemistry based on trans¬acetalization. Solvent-free melt polymerization via trans-acetalization exhibited some advantages over the trans-esterification or trans-etherification processes; for instance, it required substantially low temperatures, afforded faster reaction rates and absence of side reactions that could lead to crosslinked products. In the 2nd chapter, the first synthesis of hyperbranched polyacetals via this novel melt trans-acetalization polymerization process has been described. The process proceeds via the self-condensation of an AB2 type monomer carrying a hydroxyl group and a dimethylacetal unit (see Figure 1); the continuous removal of low boiling methanol drives the equilibrium towards polymer formation. Here, since the incipient carbocation is stabilized by a neighbouring oxygen atom, it has a substantially lower reactivity and hence does not take part in the electrophilic aromatic substitution; therefore, per-alkylation of the monomer was not required to prevent crosslinking, unlike in the case of the melt trans-etherification process developed earlier.
Figure1. Synthesis of hyperbranched polyacetals via trans-acetalization polymerization; different types of units, namely dendtritic (D), linear (L) and terminal (T) units are shown.
We studied the degradation behaviour of the solid polymer in an aqueous buffer solution having a pH of 4. Due to the susceptibility of the acetal linkages to hydrolysis, the polymer degrades readily under these mildly acidic conditions to yield 4-hydroxymethyl benzaldehyde as the primary product. After observing the fast degradation kinetics of the hyperbranched polyacetal, we developed approaches to control the rate of degradation. Interestingly, because of the unique topology of hyperbranched structures, the rate of polymer degradation was readily tuned by changing just the nature monomer; longer chain dialkylacetals, such as dibutyl- and dihexylacetals based monomers yielded hyperbranched polymers bearing longer alkyl groups at their molecular periphery. The highly branched topology and the relatively high volume-fraction of the terminal alkyl groups resulted in a significant lowering of the ingress rates of the aqueous reagents to the loci of degradation and, consequently, the degradation rates of the polymers were dramatically influenced by the hydrophobic nature of the terminal alkyl substituents. In an effort to understand this, we performed the degradation studies in solution state, where all three polymers showed almost same rate of degradation. The simple synthesis and easy tuneability of the degradation rates make these materials fairly attractive candidates for use as degradable scaffolds.
As already mentioned, the main difference between dendrimers and hyperbranched polymers is that HBPs carry a large number of statistically distributed linear defects. The origin of these linear segments is single step statistically random growth process. There are three kinds of linkages present in the HB structure. For a HB polymer generated from condensation polymerization of an AB2 monomer, these three kinds of linkages are: (i) the linkages where both the B groups have reacted is called a dendritic (D) unit, (ii) linkages where one of the B group has reacted is called a linear (L) unit, and (iii) linkages where both the B groups remain unreacted is called a terminal (T) unit. The defect levels in hyperbranched polymers is quantified by a parameter called degree of branching (DB), which is mole-fraction of dendritic and terminal units with respect to all types of repeat units. In a typical single step AB2 polycondensation process the DB value usually is around 0.5. The strategy most commonly used to achieve high DB values, specifically while using AB2 type self-condensations, is to design an AB2 monomer wherein the reaction of the first B-group leads to an enhancement of the reactivity of the second one. In the 3rd chapter the challenge of synthesizing defect-free hyperbranched polythioacetal has been addressed. In this study, it was shown that an AB2 monomer carrying a dimethylacetal unit and a benzyl thiol group undergoes a rapid self-condensation in the melt under acid-catalysis to yield a hyperbranched polydithioacetal (Figure 2a). By analyzing 1H, 13C, hetero-correlation NMR spectra and by comparison of the NMR spectrum of the polymer with those of model compounds, it was established that the HB polydithioacetals do not contain any linear defects. Furthermore, to understand the origin of defect-free structure, model reactions between dimethylacetal of tolualdehyde and benzyl mercaptan (Figure 2b) were carried out. NMR studies using of these model reactions reveal that the intermediate monothioacetal is relatively unstable under the polymerization conditions and transforms rapidly to the dithioacetal (Figure 2c); since this second step occurs irreversibly towards polymer formation, it leads to a defect-free hyperbranched dithioacetal. Isothermal TGA analysis proved to be an effective tool for monitoring the kinetics of the melt polymerization; these studies revealed that the formation of the polydithioacetal is significantly faster than previously studied polyacetal polymerization, and in the former case two distinct kinetic steps are clearly evident.
Figure 2. (a) Synthesis of defect-free hyperbranched polythioacetal; chemical structure of monomer and hyperbranched polydithioacetal; (b) model reaction to probe the unstable intermediate, and (c) variation of the concentration of different species during the model reaction as a function of time showing the appearance and disappearance of unstable intermediate.
One of the major differences between linear and hyperbranched polymers is the availability of large number of accessible terminal groups in the latter. Several properties of the hyperbranched polymers are known to be influenced by the nature of the peripheral groups. Of the many methods that have been designed to functionalize the periphery of HBPs, AB2 + A type copolymerization is one of the most readily implementable.
Figure 3. (a) Peripheral modification of hyperbranched polydithioacetal using trans-thiocetalization; (b) schematic representation of the sulphur rich hyperbranched polythioacetal having C-22 alkyl chains on its periphery and (c) TEM images of gold nanoparticle synthesized and stabilized via C-22 functionalized hyperbranched polythioacetal.
In chapter 3, the synthesis of a defect-free hypebranched polymer via trans-thiocetalization method was described; these polymers possessed only two kinds of units, namely terminal dimethylacetal groups and dendritic dithioacetal units. Because of the difference in reactivity between the dendritic (D) and terminal (T) units, the terminal groups alone was completely transformed, under acid-catalyzed conditions, to a dithioacetal unit by reaction with a variety of thiols, (Figure 3a) such as dodecanethiol, benzyl mercaptan, ethyl, 3-mercaptopropionate etc.; this transformation of the periphery was shown to be quantitative. One unique feature of this hyperbranched polydithioacetal is the high sulfur content; in order to exploit this aspect, the periphery was selectively transformed with docosyl (C-22) segments, and these sulfur-rich hydrophobically capped hyperscaffolds were utilized to stabilize gold nanoparticles in non-polar solvents (Figure 3b and 3c.) The Au-NPs, thus prepared, were characterized by UV-Visible spectroscopy and transmission electron microscopy; it was shown that, typically particles of about 4-5 nm were produced and they could be dried and readily re-dispersed in organic solvents.
In the final chapter of the thesis, the first synthesis of photodegradable hyperbranched polyacetals via a melt trans-acetalization polymerization method is described. The AB2 monomer was designed to carry a dimethyl acetal unit, and a nitro group placed ortho to a hydroxymethyl group (Figure 4a). Self-condensation of this AB2 monomer under melt polymerization conditions gives rise to a hyperbranched polyacetal wherein each repeat unit contains a 2-nitrobenzyl linkage which is susceptible to photolytic degradation upon exposure to 365 nm light.
Figure 4. (a) Synthesis of photodegradable hyperbranched nitro polyacetal; (b) scanning electron micrograph of the positive pattern obtained from hyperbranched nitro-polyacetal; (c) synthesis of alkyne-azide clickable hyperbranched nitro polyacetal; and (d) clicking onto the reactive micropatterns.
Irradiation with UV light causes the photodegradation of the polymer leading to the formation of 2-nitroso terephthalaldehyde and other low molecular weight oligomeric species. Exploiting this photodegradability, the use of this HBP as a positive photoresist to generate micron-size patterns has been demonstrated (Figure 4b); furthermore, changing the terminal groups from dimethyl acetal to dipropargyl acetal (Figure 4c), permitted the generation of patterned substrates that can be clicked with any desired functionality using the azide-yne click reaction. This last feature is unprecedented and provides a potentially quick handle to create functionalizable patterned surfaces. | en_US |
