Mitochondria-targeting cyclometallated rhodium(iii) complexes appended with two rhodamine units as Type I photosensitisers for bioimaging and photocytotoxicity applications by inducing pyroptosis

Katherine Gui-Min Jiang; Guang-Xi Xu; Lawrence Cho-Cheung Lee; Fangfang Wei; Siye Wu; Keith Man-Chung Wong; Kenneth Kam-Wing Lo

doi:10.1039/d5sc09339b

Mitochondria-targeting cyclometallated rhodium(iii) complexes appended with two rhodamine units as Type I photosensitisers for bioimaging and photocytotoxicity applications by inducing pyroptosis

Katherine Gui-Min Jiang
, Guang-Xi Xu
, Lawrence Cho-Cheung Lee
, Fangfang Wei
, Siye Wu
, Keith Man-Chung Wong^*
, Kenneth Kam-Wing Lo^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

2 Citations (Scopus)

1 Downloads (CityUHK Scholars)

Abstract

Cyclometallated rhodium(iii) complexes have been underexplored as photosensitisers due to their low-lying d–d excited states, which result in weak visible-light absorption and non-emissive properties, coupled with a modest heavy atom effect that limits reactive oxygen species (ROS) generation. In this work, a series of cyclometallated rhodium(iii) polypyridine complexes appended with two rhodamine units [Rh(N^C)₂(bpy-diRho)](PF₆)₃ was rationally designed as Type I photosensitisers. These complexes exhibited intense absorption in the visible region and moderate rhodamine fluorescence in solution upon photoexcitation. Time-resolved transient absorption spectroscopy revealed a long-lived rhodamine-based triplet excited state as the lowest-lying excited state in this hybrid system, which is attributed to the presence of the rhodium(iii) centre and is responsible for ROS photosensitisation. Notably, these rhodium(iii) complexes efficiently generated superoxide anion (O₂˙⁻) and hydroxyl (HO˙) radicals via the Type I pathway upon photoirradiation, likely via intramolecular electron transfer between the two adjacent excited rhodamine units within the complex to form radical cation and anion. Cellular colocalisation studies demonstrated that these complexes predominantly accumulated in mitochondria, where the photosensitised ROS triggered significant mitochondrial dysfunction, resulting in their outstanding photocytotoxicity under both normoxic and CoCl₂-induced hypoxic conditions. Further mechanistic investigations revealed that the photoinduced mitochondrial ROS generation triggered cancer cell death via gasdermin D-mediated pyroptosis. This rhodium(iii)–dirhodamine system further explores the utilisation of rhodium(iii) complexes as phototheranostic agents and underscores their potential in this role. This journal is © The Royal Society of Chemistry, 2026

Original language	English
Pages (from-to)	8197-8207
Number of pages	11
Journal	Chemical Science
Volume	17
Issue number	16
Online published	5 Mar 2026
DOIs	https://doi.org/10.1039/d5sc09339b
Publication status	Published - 29 Apr 2026

Funding

We thank the Hong Kong Research Grants Council (project no. CityU 11317022, CityU 11309423, CityU 11304524 and C7075-21GF), the Hong Kong Research Grants Council and National Natural Science Foundation of China (project no. N_CityU104/21), the National Natural Science Foundation of China (grant no. 21771099) and the Science, Technology and Innovation Commission of Shenzhen Municipality (grant no. JCYJ20190809165411528) for financial support. We also acknowledge funding support from the “Laboratory for Synthetic Chemistry and Chemical Biology” under the Health@InnoHK Programme launched by Innovation and Technology Commission, the Government of Hong Kong SAR, P. R. China. We are also grateful to Dr Jie Wang for his help in biological studies. K. G.-M. J. acknowledges the receipt of a Postgraduate Studentship administered by City University of Hong Kong and Southern University of Science and Technology.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Publisher's Copyright Statement

This full text is made available under CC-BY-NC 4.0. https://creativecommons.org/licenses/by-nc/4.0/

RGC Funding Information

RGC-funded

Access Output

10.1039/d5sc09339b

450647881.pdfFinal Published version, 3.63 MBLicence: CC BY-NC

Other Access Options

Check CityUHK Library

Permanent Link

Right click to copy link

Cite this

@article{3078f6e76f704b9c9450ace016854144,

title = "Mitochondria-targeting cyclometallated rhodium(iii) complexes appended with two rhodamine units as Type I photosensitisers for bioimaging and photocytotoxicity applications by inducing pyroptosis",

abstract = "Cyclometallated rhodium(iii) complexes have been underexplored as photosensitisers due to their low-lying d–d excited states, which result in weak visible-light absorption and non-emissive properties, coupled with a modest heavy atom effect that limits reactive oxygen species (ROS) generation. In this work, a series of cyclometallated rhodium(iii) polypyridine complexes appended with two rhodamine units [Rh(N\textasciicircum{}C)2(bpy-diRho)](PF6)3 was rationally designed as Type I photosensitisers. These complexes exhibited intense absorption in the visible region and moderate rhodamine fluorescence in solution upon photoexcitation. Time-resolved transient absorption spectroscopy revealed a long-lived rhodamine-based triplet excited state as the lowest-lying excited state in this hybrid system, which is attributed to the presence of the rhodium(iii) centre and is responsible for ROS photosensitisation. Notably, these rhodium(iii) complexes efficiently generated superoxide anion (O2˙−) and hydroxyl (HO˙) radicals via the Type I pathway upon photoirradiation, likely via intramolecular electron transfer between the two adjacent excited rhodamine units within the complex to form radical cation and anion. Cellular colocalisation studies demonstrated that these complexes predominantly accumulated in mitochondria, where the photosensitised ROS triggered significant mitochondrial dysfunction, resulting in their outstanding photocytotoxicity under both normoxic and CoCl2-induced hypoxic conditions. Further mechanistic investigations revealed that the photoinduced mitochondrial ROS generation triggered cancer cell death via gasdermin D-mediated pyroptosis. This rhodium(iii)–dirhodamine system further explores the utilisation of rhodium(iii) complexes as phototheranostic agents and underscores their potential in this role. This journal is {\textcopyright} The Royal Society of Chemistry, 2026",

author = "Jiang, \{Katherine Gui-Min\} and Guang-Xi Xu and Lee, \{Lawrence Cho-Cheung\} and Fangfang Wei and Siye Wu and Wong, \{Keith Man-Chung\} and Lo, \{Kenneth Kam-Wing\}",

year = "2026",

month = apr,

day = "29",

doi = "10.1039/d5sc09339b",

language = "English",

volume = "17",

pages = "8197--8207",

journal = "Chemical Science",

issn = "2041-6520",

publisher = "Royal Society of Chemistry",

number = "16",

}

Mitochondria-targeting cyclometallated rhodium(iii) complexes appended with two rhodamine units as Type I photosensitisers for bioimaging and photocytotoxicity applications by inducing pyroptosis. / Jiang, Katherine Gui-Min ; Xu, Guang-Xi ; Lee, Lawrence Cho-Cheung et al.
In: Chemical Science, Vol. 17, No. 16, 29.04.2026, p. 8197-8207.

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

TY - JOUR

T1 - Mitochondria-targeting cyclometallated rhodium(iii) complexes appended with two rhodamine units as Type I photosensitisers for bioimaging and photocytotoxicity applications by inducing pyroptosis

AU - Jiang, Katherine Gui-Min

AU - Xu, Guang-Xi

AU - Lee, Lawrence Cho-Cheung

AU - Wei, Fangfang

AU - Wu, Siye

AU - Wong, Keith Man-Chung

AU - Lo, Kenneth Kam-Wing

PY - 2026/4/29

Y1 - 2026/4/29

N2 - Cyclometallated rhodium(iii) complexes have been underexplored as photosensitisers due to their low-lying d–d excited states, which result in weak visible-light absorption and non-emissive properties, coupled with a modest heavy atom effect that limits reactive oxygen species (ROS) generation. In this work, a series of cyclometallated rhodium(iii) polypyridine complexes appended with two rhodamine units [Rh(N^C)2(bpy-diRho)](PF6)3 was rationally designed as Type I photosensitisers. These complexes exhibited intense absorption in the visible region and moderate rhodamine fluorescence in solution upon photoexcitation. Time-resolved transient absorption spectroscopy revealed a long-lived rhodamine-based triplet excited state as the lowest-lying excited state in this hybrid system, which is attributed to the presence of the rhodium(iii) centre and is responsible for ROS photosensitisation. Notably, these rhodium(iii) complexes efficiently generated superoxide anion (O2˙−) and hydroxyl (HO˙) radicals via the Type I pathway upon photoirradiation, likely via intramolecular electron transfer between the two adjacent excited rhodamine units within the complex to form radical cation and anion. Cellular colocalisation studies demonstrated that these complexes predominantly accumulated in mitochondria, where the photosensitised ROS triggered significant mitochondrial dysfunction, resulting in their outstanding photocytotoxicity under both normoxic and CoCl2-induced hypoxic conditions. Further mechanistic investigations revealed that the photoinduced mitochondrial ROS generation triggered cancer cell death via gasdermin D-mediated pyroptosis. This rhodium(iii)–dirhodamine system further explores the utilisation of rhodium(iii) complexes as phototheranostic agents and underscores their potential in this role. This journal is © The Royal Society of Chemistry, 2026

AB - Cyclometallated rhodium(iii) complexes have been underexplored as photosensitisers due to their low-lying d–d excited states, which result in weak visible-light absorption and non-emissive properties, coupled with a modest heavy atom effect that limits reactive oxygen species (ROS) generation. In this work, a series of cyclometallated rhodium(iii) polypyridine complexes appended with two rhodamine units [Rh(N^C)2(bpy-diRho)](PF6)3 was rationally designed as Type I photosensitisers. These complexes exhibited intense absorption in the visible region and moderate rhodamine fluorescence in solution upon photoexcitation. Time-resolved transient absorption spectroscopy revealed a long-lived rhodamine-based triplet excited state as the lowest-lying excited state in this hybrid system, which is attributed to the presence of the rhodium(iii) centre and is responsible for ROS photosensitisation. Notably, these rhodium(iii) complexes efficiently generated superoxide anion (O2˙−) and hydroxyl (HO˙) radicals via the Type I pathway upon photoirradiation, likely via intramolecular electron transfer between the two adjacent excited rhodamine units within the complex to form radical cation and anion. Cellular colocalisation studies demonstrated that these complexes predominantly accumulated in mitochondria, where the photosensitised ROS triggered significant mitochondrial dysfunction, resulting in their outstanding photocytotoxicity under both normoxic and CoCl2-induced hypoxic conditions. Further mechanistic investigations revealed that the photoinduced mitochondrial ROS generation triggered cancer cell death via gasdermin D-mediated pyroptosis. This rhodium(iii)–dirhodamine system further explores the utilisation of rhodium(iii) complexes as phototheranostic agents and underscores their potential in this role. This journal is © The Royal Society of Chemistry, 2026

UR - https://www.scopus.com/pages/publications/105031646561

UR - https://www.scopus.com/pages/publications/105031646561#tab=impact

U2 - 10.1039/d5sc09339b

DO - 10.1039/d5sc09339b

M3 - RGC 21 - Publication in refereed journal

SN - 2041-6520

VL - 17

SP - 8197

EP - 8207

JO - Chemical Science

JF - Chemical Science

IS - 16

ER -

Mitochondria-targeting cyclometallated rhodium(iii) complexes appended with two rhodamine units as Type I photosensitisers for bioimaging and photocytotoxicity applications by inducing pyroptosis

Abstract

Funding

UN SDGs

Publisher's Copyright Statement

RGC Funding Information

Access Output

Other Access Options

Permanent Link

Other Files and Links

Fingerprint

GRF: Development of Stimuli-responsive Chemiluminescent Transition Metal Complexes as Activatable Theranostic Agents for Cancer Imaging and Photodynamic Therapy

GRF: Strategic Design of Photofunctional Transition Metal Complexes as Photoinducers to Trigger Cancer-Selective Immunogenic Cell Death

GRF: Targeting N-terminal Cysteine Residues with Photofunctional Transition Metal Complexes for Site-specific Bioconjugation, Live-cell Imaging, and Phototherapeutic Applications

Cite this

Mitochondria-targeting cyclometallated rhodium(iii) complexes appended with two rhodamine units as Type I photosensitisers for bioimaging and photocytotoxicity applications by inducing pyroptosis

Abstract

Funding

UN SDGs

Publisher's Copyright Statement

RGC Funding Information

Access Output

Other Access Options

Permanent Link

Other Files and Links

Fingerprint

Projects

GRF: Development of Stimuli-responsive Chemiluminescent Transition Metal Complexes as Activatable Theranostic Agents for Cancer Imaging and Photodynamic Therapy

GRF: Strategic Design of Photofunctional Transition Metal Complexes as Photoinducers to Trigger Cancer-Selective Immunogenic Cell Death

GRF: Targeting N-terminal Cysteine Residues with Photofunctional Transition Metal Complexes for Site-specific Bioconjugation, Live-cell Imaging, and Phototherapeutic Applications

Cite this