Article pubs.acs.org/JPCB
Computational Design of Two-Photon Fluorescent Probes for Intracellular Free Zinc Ions Dan Wang,† Jing-fu Guo,‡ Ai-Min Ren,*,† Shuang Huang,§ Li Zhang,† and Ji-Kang Feng† †
State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun, 130023 People’s Republic of China ‡ School of Physics, Northeast Normal University, Changchun, 130021 People’s Republic of China § School of Mathematics and Physics, Changzhou University, Changzhou, 213164 People’s Republic of China S Supporting Information *
ABSTRACT: Two-photon fluorescence probes used in two-photon fluorescence microscopy (TPM) can achieve intact tissue imaging without destruction. Therefore, for a long time, TPM has been an important tool in biology and medicine. In this background via a quantum chemical method, a series of zinc ion probe molecules using N,N-di(2-picolyl)ethylenediamine (DPEN) as the recognition group were studied, which are based on the photoinduced electron transfer (PET) mechanism. The fact that the one-photon absorption peak is almost unchanged and the fluorescence emission intensity increased significantly upon coordination with a zinc ion reveals that these probes can be PET fluorescent bioimaging reagents. And it is predicted that when the chemically modified probe molecule is incorporated with Zn2+, the two-photon absorption (TPA) cross-section (δmax) will greatly increase and the TPA peak will be in the near-infrared region. The molecules after changing the fluorophore become more suitable for probing Zn2+ in vivo, and a modification at the end of the fluorophore can fine-tune the fluorescence and TPA properties. The detailed investigations will provide a theoretical basis for synthesizing new zinc-ionresponsive two-photon fluorescent probes.
1. INTRODUCTION Zinc is the second most abundant transition metal.1,2 In the brain, presynaptic vesicles store 5−20% of the total Zn2+, and the hippocampus has the highest intracellular free Zn2+ ([Zn2+]i).3,4 Zn2+ plays a key role in synaptic plasticity and modulating brain excitability.5 Maintaining [Zn2+]i homeostasis is vital for proper brain function. Neurological disorders are caused by an imbalance of [Zn2+]i, such as Alzheimer’s and Parkinson’s diseases.6−8 On one hand, the mitochondria controls the [Zn2+]i homeostasis through evoking [Zn2+]i increases.9−11 On the other hand, an elevated concentration of intramitochondrial Zn2+ ([Zn2+]m) can lead to mitochondrial dysfunction and the generation of reactive oxygen species (ROS).9−11 So monitoring [Zn2+]m in intact brain tissues becomes the key to understanding the physiology of Zn2+ in the brain. However, due to the colorlessness and magnetic silence of Zn2+, it is difficult to accurately understand the biological roles of Zn2+.12,13 A variety of one-photon fluorescent (OPF) probes derived from quinoline (TSQ, Zinquin, TFLZn, QZ1, and QZ2) and fluorescein (FluoZn-3, Znpyr, and ZnAF) have been developed to understand the role of Zn2+ ions in physiology,14−22 and relatively short excitation wavelengths (
Computational Design of Two-Photon Fluorescent Probes for Intracellular Free Zinc Ions Dan Wang,† Jing-fu Guo,‡ Ai-Min Ren,*,† Shuang Huang,§ Li Zhang,† and Ji-Kang Feng† †
State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun, 130023 People’s Republic of China ‡ School of Physics, Northeast Normal University, Changchun, 130021 People’s Republic of China § School of Mathematics and Physics, Changzhou University, Changzhou, 213164 People’s Republic of China S Supporting Information *
ABSTRACT: Two-photon fluorescence probes used in two-photon fluorescence microscopy (TPM) can achieve intact tissue imaging without destruction. Therefore, for a long time, TPM has been an important tool in biology and medicine. In this background via a quantum chemical method, a series of zinc ion probe molecules using N,N-di(2-picolyl)ethylenediamine (DPEN) as the recognition group were studied, which are based on the photoinduced electron transfer (PET) mechanism. The fact that the one-photon absorption peak is almost unchanged and the fluorescence emission intensity increased significantly upon coordination with a zinc ion reveals that these probes can be PET fluorescent bioimaging reagents. And it is predicted that when the chemically modified probe molecule is incorporated with Zn2+, the two-photon absorption (TPA) cross-section (δmax) will greatly increase and the TPA peak will be in the near-infrared region. The molecules after changing the fluorophore become more suitable for probing Zn2+ in vivo, and a modification at the end of the fluorophore can fine-tune the fluorescence and TPA properties. The detailed investigations will provide a theoretical basis for synthesizing new zinc-ionresponsive two-photon fluorescent probes.
1. INTRODUCTION Zinc is the second most abundant transition metal.1,2 In the brain, presynaptic vesicles store 5−20% of the total Zn2+, and the hippocampus has the highest intracellular free Zn2+ ([Zn2+]i).3,4 Zn2+ plays a key role in synaptic plasticity and modulating brain excitability.5 Maintaining [Zn2+]i homeostasis is vital for proper brain function. Neurological disorders are caused by an imbalance of [Zn2+]i, such as Alzheimer’s and Parkinson’s diseases.6−8 On one hand, the mitochondria controls the [Zn2+]i homeostasis through evoking [Zn2+]i increases.9−11 On the other hand, an elevated concentration of intramitochondrial Zn2+ ([Zn2+]m) can lead to mitochondrial dysfunction and the generation of reactive oxygen species (ROS).9−11 So monitoring [Zn2+]m in intact brain tissues becomes the key to understanding the physiology of Zn2+ in the brain. However, due to the colorlessness and magnetic silence of Zn2+, it is difficult to accurately understand the biological roles of Zn2+.12,13 A variety of one-photon fluorescent (OPF) probes derived from quinoline (TSQ, Zinquin, TFLZn, QZ1, and QZ2) and fluorescein (FluoZn-3, Znpyr, and ZnAF) have been developed to understand the role of Zn2+ ions in physiology,14−22 and relatively short excitation wavelengths (
