# A Heptamethine Cyanine-Based Near-Infrared Optical Sensor for Copper(II) Detection in Aqueous Solutions and Living Cells

## TL;DR

A new near-infrared sensor called IRPhen can detect copper ions in water and living cells with high sensitivity and selectivity.

## Contribution

IRPhen is a novel heptamethine cyanine-based NIR optical sensor for selective and sensitive Cu2+ detection.

## Key findings

- IRPhen binds Cu2+ with a binding constant of 1.3 × 106 M−1 and a detection limit of 0.286 µM.
- The sensor is cell-permeable and detected Cu2+ changes in living fibroblast cells using confocal microscopy.
- IRPhen shows stability across physiological pH and outperforms other metal ion detection methods.

## Abstract

Copper ions are essential trace elements that play critical roles in redox reactions, signal transduction, energy metabolism, and regulation of the central nervous system. However, excess copper can induce cytotoxicity and contribute to various pathological conditions, highlighting the need for sensitive and selective detection methods. We report a novel near-infrared (NIR) optical sensor, IRPhen, based on a heptamethine cyanine scaffold conjugated with a 1,10-phenanthroline Cu2+-binding receptor. IRPhen exhibits strong NIR absorption and emission (Ex: 750 nm, Em: 808 nm), high sensitivity, and good selectivity toward Cu2+ over competing metal ions. Spectroscopic studies revealed a rapid, reversible 1:1 binding interaction with a binding constant of 1.3 × 106 M−1 and a detection limit of 0.286 µM. The probe demonstrated excellent stability across physiological pH ranges and maintained its performance under competitive conditions. Importantly, IRPhen is cell-permeable and capable of detecting dynamic Cu2+ changes in living fibroblast (WS1) cells using confocal microscopy. This sensor design offers a versatile platform for developing NIR optical sensors to study copper homeostasis, elucidating copper-related biological mechanisms, and potentially developing similar NIR probes for other biologically relevant metal ions.