Skip to main content

Effect of molecular characteristics on cellular uptake, subcellular localization, and phototoxicity of Zn(II) N-alkylpyridylporphyrins.

Publication ,  Journal Article
Ezzeddine, R; Al-Banaw, A; Tovmasyan, A; Craik, JD; Batinic-Haberle, I; Benov, LT
Published in: J Biol Chem
December 20, 2013

Tetra-cationic Zn(II) meso-tetrakis(N-alkylpyridinium-2 (or -3 or -4)-yl)porphyrins (ZnPs) with progressively increased lipophilicity were synthesized to investigate how the tri-dimensional shape and lipophilicity of the photosensitizer (PS) affect cellular uptake, subcellular distribution, and photodynamic efficacy. The effect of the tri-dimensional shape of the molecule was studied by shifting the N-alkyl substituent attached to the pyridyl nitrogen from ortho to meta and para positions. Progressive increase of lipophilicity from shorter hydrophilic (methyl) to longer amphiphilic (hexyl) alkyl chains increased the phototoxicity of the ZnP PSs. PS efficacy was also increased for all derivatives when the alkyl substituents were shifted from ortho to meta, and from meta to para positions. Both cellular uptake and subcellular distribution of the PSs were affected by the lipophilicity and the position of the alkyl chains on the periphery of the porphyrin ring. Whereas the hydrophilic ZnPs demonstrated mostly lysosomal distribution, the amphiphilic hexyl derivatives were associated with mitochondria, endoplasmic reticulum, and plasma membrane. A comparison of hexyl isomers revealed that cellular uptake and partition into membranes followed the order para > meta > ortho. Varying the position and length of the alkyl substituents affects (i) the exposure of cationic charges for electrostatic interactions with anionic biomolecules and (ii) the lipophilicity of the molecule. The charge, lipophilicity, and the tri-dimensional shape of the PS are the major factors that determine cellular uptake, subcellular distribution, and as a consequence, the phototoxicity of the PSs.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

December 20, 2013

Volume

288

Issue

51

Start / End Page

36579 / 36588

Location

United States

Related Subject Headings

  • Zinc
  • Static Electricity
  • Radiation-Sensitizing Agents
  • Mitochondria
  • Metalloporphyrins
  • MCF-7 Cells
  • Lysosomes
  • Light
  • Isomerism
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Ezzeddine, R., Al-Banaw, A., Tovmasyan, A., Craik, J. D., Batinic-Haberle, I., & Benov, L. T. (2013). Effect of molecular characteristics on cellular uptake, subcellular localization, and phototoxicity of Zn(II) N-alkylpyridylporphyrins. J Biol Chem, 288(51), 36579–36588. https://doi.org/10.1074/jbc.M113.511642
Ezzeddine, Rima, Anwar Al-Banaw, Artak Tovmasyan, James D. Craik, Ines Batinic-Haberle, and Ludmil T. Benov. “Effect of molecular characteristics on cellular uptake, subcellular localization, and phototoxicity of Zn(II) N-alkylpyridylporphyrins.J Biol Chem 288, no. 51 (December 20, 2013): 36579–88. https://doi.org/10.1074/jbc.M113.511642.
Ezzeddine R, Al-Banaw A, Tovmasyan A, Craik JD, Batinic-Haberle I, Benov LT. Effect of molecular characteristics on cellular uptake, subcellular localization, and phototoxicity of Zn(II) N-alkylpyridylporphyrins. J Biol Chem. 2013 Dec 20;288(51):36579–88.
Ezzeddine, Rima, et al. “Effect of molecular characteristics on cellular uptake, subcellular localization, and phototoxicity of Zn(II) N-alkylpyridylporphyrins.J Biol Chem, vol. 288, no. 51, Dec. 2013, pp. 36579–88. Pubmed, doi:10.1074/jbc.M113.511642.
Ezzeddine R, Al-Banaw A, Tovmasyan A, Craik JD, Batinic-Haberle I, Benov LT. Effect of molecular characteristics on cellular uptake, subcellular localization, and phototoxicity of Zn(II) N-alkylpyridylporphyrins. J Biol Chem. 2013 Dec 20;288(51):36579–36588.

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

December 20, 2013

Volume

288

Issue

51

Start / End Page

36579 / 36588

Location

United States

Related Subject Headings

  • Zinc
  • Static Electricity
  • Radiation-Sensitizing Agents
  • Mitochondria
  • Metalloporphyrins
  • MCF-7 Cells
  • Lysosomes
  • Light
  • Isomerism
  • Humans