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Time-Resolved Spectroscopic Studies of the Photophysics and Photochemistry of Selected Statins

phillips - Posted on 25 November 2016

Project Description: 

Statin drugs like simvastatin, rosuvastatin, atorvastatin and others are among
the most widely prescribed drugs in the world since they can help with the primary and
secondary prevention of coronary heart disease. However, some statin drugs may have
adverse health effects such as subacute cutaneous lupus, dermatomyositis, lichenoid drug
eruptions, and photoallergic reactions after the patient is exposed to sunlight. It is
important to better understand how sunlight excitation of different statin drugs induces
these adverse health effects that are the result of the photochemistry of these
compounds. So far, there has been limited research to study the photophysics and
photochemistry of statin drug compounds. Some research studies have been done to
identify and characterize the photoproducts of several statin drugs. For several statins,
nanosecond time-resolved transient absorption spectroscopy investigations have directly
observed some intermediate species on the nanosecond to microsecond time-scales but
the identity and structure of these intermediates remain unclear. There are not yet any
ultrafast (femtoseconds to picoseconds) time-resolved spectroscopy experiments reported
in the literature. To gain additional and missing information about the photophysics and
photochemistry of selected statin drugs, several different types of time-resolved
spectroscopy methods will be used to directly observe and characterize the excited states,
intermediates and products from femtoseconds to final products. Femtosecond timeresolved
transient absorption spectroscopy will be used to examine the excited states and
intermediates to provide new insight into the early time photophysics and
photochemistry of these compounds. Next, nanosecond time-resolved transient
absorption spectroscopy and photoproduct analysis experiments will be done. This work
combined with the femtosecond time-resolved spectra will enable a comprehensive
characterization of the photophysics and photochemistry from initial excitation on the
femtosecond time scale all the way to formation of the final products for the statin
compounds examined. To gain missing information about the structure and properties
of the excited states and intermediate species, picosecond and nanosecond time-resolved
resonance Raman experiments will be performed for the statin molecules of interest.
This new data will help to clearly identify as well as to elucidate the structure and
properties of the excited states and intermediate species involved in the photophysics
and photochemistry of the statin compounds investigated. The new information for the
photophysics, photochemistry, excited states and reactive intermediates for the statin
compounds examined in this project should be useful for future research to help design
and develop new and improved statin compounds for a variety of applications.

Researcher name: 
David Lee Phillips
Researcher position: 
Chair Professor
Researcher department: 
Department of Chemistry
Researcher email: 
phillips@hku.hk
Research Project Details
Project Duration: 
09/2016 to 08/2019
Project Significance: 
Statins have found a wide range of uses that include being some of the most widely used drugs for the primary and secondary prevention of coronary heart disease (example drugs include simvastatin, lovastatin, rosuvastatin and atorvastatin) as well as some statins like blebbistatin being Myosin II inhibitors that can be used in biological applications that require organ, tissue, or single-cell immobilization like optical imaging of membrane potentials and intracellular calcium signaling in the heart. However, many statins contain chromophores that can be excited by absorption of sunlight so as to cause adverse photochemical effects like phototoxicity, photoallerigic reactions, dermatomyositis and others which limit their use for many patients and biological imaging applications. So far there has been limited work done to understand the photophysics and photochemistry of statins with only several reports of product analysis studies and in some cases nanosecond time-resolved transient absorption spectroscopy investigations that observed one or two intermediates whose structure and identity remain ambiguous. There is clearly an important need to gain more information and a better understanding for the photophysics and photochemistry of statins in aqueous environments so as to elucidate the causes of the adverse photo-induced effects of statins after exposure to sunlight. To address this, we propose to utilize several different kinds of time-resolved spectroscopic methods such as femtosecond and nanosecond time-resolved transient absorption (fs-TA and ns-TA) and also picosecond and nanosecond time-resolved resonance Raman spectroscopy (ps- TR3 and ns-TR3) to directly observe and characterize the excited states and intermediates involved in the photophysics and photochemistry of the selected statin compounds to be investigated in this project. This new and more extensive time-resolved spectroscopic data will be able to help develop an improved understanding of the identity, nature and properties of the excited states and intermediates involved in the photochemistry of interest. This new information can also be employed to determine reaction mechanisms and structure-function relationships that can be utilized to aid the design and development of new statin compounds with lower photo-induced adverse effects and improved photostability in the future.
Results Achieved: 
We have obtained experimental and computational results for the photochemistry of Blebbistatin and deoxyblebbistatin and are preparing manuscripts to be submitted for publication.
Remarks: 
None