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Evaluation of poly(amidoamine) dendrimers as potential carriers of iminodiacetic derivatives using solubility studies and 2D-NOESY NMR spectroscopy.

Markowicz M, Szymański P, Ciszewski M, Kłys A, Mikiciuk-Olasik E - J Biol Phys (2012)

Bottom Line: We reported that PAMAM dendrimers contribute to significant solubility enhancement of iminodiacetic acid analogues.The 2D-NOESY analysis revealed interactions between the primary amine groups of PAMAM dendrimers and the analogues of iminodiacetic acid.The results of solubility studies together with (1)H NMR and 2D-NOESY experiments suggest that the interactions between PAMAM dendrimers of generation 1-4 and derivatives of iminodiacetic acid are based on electrostatic interactions and internal encapsulation.Electronic supplementary material The online version of this article (doi:10.1007/s10867-012-9277-5) contains supplementary material, which is available to authorized users.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Chemistry and Drug Analysis, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland.

ABSTRACT
The interactions between dendrimers and different types of drugs are nowadays one of the most actively investigated areas of the pharmaceutical sciences. The interactions between dendrimers and drugs can be divided into: internal encapsulation, external electrostatic interaction, and covalent conjugation. In the present study, we investigated the potential of poly(amidoamine) (PAMAM) dendrimers for solubility of four iminodiacetic acid derivatives. We reported that PAMAM dendrimers contribute to significant solubility enhancement of iminodiacetic acid analogues. The nature of the dendrimer-drug complexes was investigated by (1)H NMR and 2D-NOESY spectroscopy. The (1)H NMR analysis proved that the water-soluble supramolecular structure of the complex was formed on the basis of ionic interactions between terminal amine groups of dendrimers and carboxyl groups of drug molecules, as well as internal encapsulation. The 2D-NOESY analysis revealed interactions between the primary amine groups of PAMAM dendrimers and the analogues of iminodiacetic acid. The results of solubility studies together with (1)H NMR and 2D-NOESY experiments suggest that the interactions between PAMAM dendrimers of generation 1-4 and derivatives of iminodiacetic acid are based on electrostatic interactions and internal encapsulation.Electronic supplementary material The online version of this article (doi:10.1007/s10867-012-9277-5) contains supplementary material, which is available to authorized users.

No MeSH data available.


1H NMR spectra of compound 2, G2 PAMAM dendrimer and the complex of compound 2 with G2 PAMAM dendrimer
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Fig6: 1H NMR spectra of compound 2, G2 PAMAM dendrimer and the complex of compound 2 with G2 PAMAM dendrimer

Mentions: In complexes between compound 2 and the G2 PAMAM dendrimer, significant changes in chemical shifts of CH2 protons (b′ and d′) of the G2 dendrimer are observed. These downfield changes of chemical shift of methylene protons are localized at the outermost layer of the G2 dendrimer (from 2.56 to 2.86 ppm and from 3.07 to 3.29 ppm, respectively) and provide evidence of ionic interactions between terminal protonated amine groups of the dendrimer and carboxylic acid groups of compound 1. This may be explained by the fact that electron density around the cation (protonated amine group) decreases. The interior methylene protons a, b, c, and d also exhibit downfield shifts. However, this type of change should not be assigned to the electrostatic interaction because these protons are too far away from the surface of the dendrimer. It seems to be due to the quaternization of amine groups in the interior of the G2 dendrimer. This observation suggests that the internal electrostatic interactions may also contribute to the encapsulation of guests with low pKa values into the dendrimer structure. Figure 6 presents 1H NMR spectra of compound 2, PAMAM dendrimer G2 and the complex of compound 2 with PAMAM G2 dendrimer.Fig. 6


Evaluation of poly(amidoamine) dendrimers as potential carriers of iminodiacetic derivatives using solubility studies and 2D-NOESY NMR spectroscopy.

Markowicz M, Szymański P, Ciszewski M, Kłys A, Mikiciuk-Olasik E - J Biol Phys (2012)

1H NMR spectra of compound 2, G2 PAMAM dendrimer and the complex of compound 2 with G2 PAMAM dendrimer
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3473130&req=5

Fig6: 1H NMR spectra of compound 2, G2 PAMAM dendrimer and the complex of compound 2 with G2 PAMAM dendrimer
Mentions: In complexes between compound 2 and the G2 PAMAM dendrimer, significant changes in chemical shifts of CH2 protons (b′ and d′) of the G2 dendrimer are observed. These downfield changes of chemical shift of methylene protons are localized at the outermost layer of the G2 dendrimer (from 2.56 to 2.86 ppm and from 3.07 to 3.29 ppm, respectively) and provide evidence of ionic interactions between terminal protonated amine groups of the dendrimer and carboxylic acid groups of compound 1. This may be explained by the fact that electron density around the cation (protonated amine group) decreases. The interior methylene protons a, b, c, and d also exhibit downfield shifts. However, this type of change should not be assigned to the electrostatic interaction because these protons are too far away from the surface of the dendrimer. It seems to be due to the quaternization of amine groups in the interior of the G2 dendrimer. This observation suggests that the internal electrostatic interactions may also contribute to the encapsulation of guests with low pKa values into the dendrimer structure. Figure 6 presents 1H NMR spectra of compound 2, PAMAM dendrimer G2 and the complex of compound 2 with PAMAM G2 dendrimer.Fig. 6

Bottom Line: We reported that PAMAM dendrimers contribute to significant solubility enhancement of iminodiacetic acid analogues.The 2D-NOESY analysis revealed interactions between the primary amine groups of PAMAM dendrimers and the analogues of iminodiacetic acid.The results of solubility studies together with (1)H NMR and 2D-NOESY experiments suggest that the interactions between PAMAM dendrimers of generation 1-4 and derivatives of iminodiacetic acid are based on electrostatic interactions and internal encapsulation.Electronic supplementary material The online version of this article (doi:10.1007/s10867-012-9277-5) contains supplementary material, which is available to authorized users.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Chemistry and Drug Analysis, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland.

ABSTRACT
The interactions between dendrimers and different types of drugs are nowadays one of the most actively investigated areas of the pharmaceutical sciences. The interactions between dendrimers and drugs can be divided into: internal encapsulation, external electrostatic interaction, and covalent conjugation. In the present study, we investigated the potential of poly(amidoamine) (PAMAM) dendrimers for solubility of four iminodiacetic acid derivatives. We reported that PAMAM dendrimers contribute to significant solubility enhancement of iminodiacetic acid analogues. The nature of the dendrimer-drug complexes was investigated by (1)H NMR and 2D-NOESY spectroscopy. The (1)H NMR analysis proved that the water-soluble supramolecular structure of the complex was formed on the basis of ionic interactions between terminal amine groups of dendrimers and carboxyl groups of drug molecules, as well as internal encapsulation. The 2D-NOESY analysis revealed interactions between the primary amine groups of PAMAM dendrimers and the analogues of iminodiacetic acid. The results of solubility studies together with (1)H NMR and 2D-NOESY experiments suggest that the interactions between PAMAM dendrimers of generation 1-4 and derivatives of iminodiacetic acid are based on electrostatic interactions and internal encapsulation.Electronic supplementary material The online version of this article (doi:10.1007/s10867-012-9277-5) contains supplementary material, which is available to authorized users.

No MeSH data available.