Microwave assisted synthesis of PAMAM type dendrimers and their analytical applications

Dendrimers are highly branched, star shaped and three dimensional macromolecules with nanometer scale. Their structural composition and controlled synthesis allow them to be designed with different shapes and sizes with various interior cores and surface groups. Surface modification of dendrimers affects their physical or chemical properties such as solubility, chelating ability, encapsulation efficiency, and absorption capacity. Depending on these attained features, dendrimers can be used for a wide range of applications including drug delivery, gene therapy, catalysis, antibacterial agents, and many others. Starting from ethylene diamine (EDA), diethylene triamine (DETA) and commercially available polymer Jeffamine® T-403 cores, amine, tris and carboxyl terminated water soluble poly (amidoamine) (PAMAM) dendrimers up to fourth generation were synthesized. Synthesis of amine and tris terminated PAMAMs were performed by new developed microwave assisted synthesis (MAS) methods. In this way, amidation step was shortened up to 30-80 min from 5-8 days while tris surface modification was shorten up to 110-130 min from two days. Amine terminated and surface modified DETA, and Jeffamine® T-403 cored PAMAMs, which are synthesized in thesis, are literaturally novel molecules. Synthesized dendrimers were purified by liquid phase polymer retention (LPR) technique and characterized by 1H NMR, 13C NMR, IR and UV-VIS spectroscopy. Dendrimers were synthesized in high purity, good yields and massive amounts in short period of time. Protonation mechanism of synthesized dendrimers were investigated by potentiometric and spectroscopic titrations. Data driven from titrations were used in pKa calculations of PAMAMs by means of computer programs Hyperquad and HypSpec. Number of absorbing species in aqueous PAMAM solutions to establish chemical equilibrium models were determined with spectral factor analysis (SPFA). Thus, without using any law of mass action, number of species present in aqueous PAMAM solutions were determined and pKa calculations were performed. A positive correlation between the number of protonated species and generation (G) of amine terminated PAMAMs was observed. By means of species distribution plots obtained from titration experiments, protonation behaviors of synthesized dendrimers were characterized. Properties of a model fourth generation Jeffamine® T-403 cored P4.NH2 dendrimer on the Co(II) binding ability and a low bioavailable drug Carvedilol (CAR) were investigated. P4.NH2-Co(II) complex and P4.NH2-CAR inclusion complex were characterized by UV-VIS spectroscopy. Stable and miscible ion pairs of CAR with internal basic tertiary amines of P4.NH2 were observed. The ability of simultaneous metal complexation of P3.NH2 and P4.NH2 was investigated with the removal of uncomplexed Cu(II), Co(II), Ni(II), Cd(II), and Zn(II) ions from metal dendrimer mixture solutions by LPR technique. Retentate metal concentrations were determined by atomic absorption spectroscopy (AAS). The effect of pH and generation number on the simultaneous removal of metal ions from different generation (P3.NH2 and P4.NH2) Jeffamine® T-403 cored PAMAM dendrimer solutions was also investigated. High affinity of both P3.NH2 and P4.NH2 towards metal ions were determined in the decreasing order of Zn(II)> Co(II)> Ni(II)> Cu(II)> Cd(II) at pH 9.0. It was observed that only the Cu(II) retention increased with the increasing generation and pH. Zn(II) and Co(II) were retained over 90% for both generations at pH 9.0. In this way, novel metal chelating abilities of polydentate P3.NH2 and P4.NH2 ligands were characterized by LPR technique and explained by extent of pronation (EOP) profiles in different pH values. It was observed that over neutral pH, P3.NH2 and P4.NH2 were stable enough to simultaneously bind Cu(II), Co(II), Ni(II), Cd(II), and Zn(II). Synthesis of Cu-DEN nanoparticles were performed from EDA, DETA and Jeffamine® T-403 cored tris and carboxyl terminated PAMAMs. Maximum metal loading capacity of these PAMAMs were determined by spectroscopic titrations. Cu-DENs were characterized by UV-VIS spectroscopy. Disappearance of 680 nm d-d transition and 270-300 nm ligand to metal charge transfer (LMCT) peak and formation of monotically increasing exponential band were used as the evidence of the successful synthesis of Cu-DENs in addition to immediate color change of dendrimer metal mixture solutions from blue to golden brown by reduction. Finally, full factorial three level experimental design was used to construct multivariate calibration models (MLR, PCR, PLS) for the simultaneous determination P2.NH2 and P3.NH2 from binary mixtures of Jeffamine® T403 cored PAMAMs by UV-VIS spectroscopy. Constructed models were compared in terms of their prediction powers from relative mean square error of prediction (RMSEP) values. Key words: Dendrimer, Poly (amidoamine) (PAMAM), microwave assisted synthesis (MAS), liquid phase retention (LPR), spectral factor analysis (SPFA), removal of metals, multivariate calibration (MLR, PCR, PLS)