Theoretical Exploration of Type I/Type II Dual Photoreactivity of Promising Ru(II) Dyads for PDT Approach

Abstract

Ru(II) dyads are a class of bioactive molecules of interest as anticancer agents obtained incorporating an organic chromophore in the light-absorbing metallic scaffold. A careful DFT and TDDFT investigation of the photophysical properties of a series of Ru(II)-polypiridyl dyads containing polythiophene chains of different lengths bound to a coordinating imidazo[4,5-f][1,10]phenanthroline ligand is herein reported. The modulation of the crucial chemical and physical properties of the photosensitizer with increasing number of thiophene units has been accurately described by investigating the UV-vis spectra and type I and type II photoreactions, also including spin-orbit coupling values (SOC). Results show that the low-lying IL states afforded as the number of thiophene ligands increases (n = 3, 4) are energetically high enough to ensure singlet oxygen production and can be also involved in electron transfer reaction, showing a dual type I/type II photeoreactivity.

Synthesis, Characterization and Photobiological Studies of Ru(II) Dyads Derived from α‐Oligothiophene Derivatives of 1,10‐Phenanthroline

“…Even when any dark cytotoxic contribution to the observed photocytotoxicity is considered, the red photobiological activity increased with π ‐expansion in this series. The theoretical basis for this phenomenon, from computational methods on related Ru(II) dyads containing thienyl groups, appears to be direct population of a low‐lying 3 IL state for n ≥ 2, but the increased organic character of these states leads to small spin‐orbit coupling (SOC) values (on the order of a few tens of cm −1 ) and thus very weak S ‐ T absorption . The fact that any red photocytotoxicity is observed at all suggests that these 3 IL states must be highly photosensitizing, particularly in the case of 3 .…”

“…In addition, Ru(II) dyads having oligothienyl‐substituted ligands with n as small as 2 exhibit long‐lived charge separation via 3 ILCT states formed by reductive quenching of the initially populated 3 MLCT state as demonstrated by Wolf and MacDonnell These 3 ILCT states can participate in electron transfer reactions with oxygen and also undergo autoionization steps to propagate chain reactions. This Type I/II dual reactivity has been explored computationally for Ru(II) dyads containing the oligothienyl‐appended imidazo[4,5‐ f ][1,10]phenanthroline (IP‐ n T) ligand, where n = 1–4 , to explain the potent in vitro PDT effects observed with certain members of this family . One example that serves to illustrate the potential of such systems in photobiological applications is [Ru(dmb) 2 (IP‐3T)]Cl 2 (dmb = 4,4′‐dimethyl‐2,2′‐bipyridine), also known as TLD1433, a Ru(II) dyad that we developed as the first Ru(II)‐based photosensitizer to enter a human clinical trial.…”

Synergistic Effects in PtII–Porphyrinoid Dyes as Candidates for a Dual‐Action Anticancer Therapy: A Theoretical Exploration

“…The small computed SOC values, although large enough to induce ISC on a nanosecond timescale, were a direct consequence of the π–π* character of the involved orbitals in the radiationless transition that lack any significant metal contribution; therefore, the well‐known “heavy atom effect” is quite irrelevant. Comparable small values have previously been computed for metallic PSs, for which the accessible ISC channels involved excited states with nearly identical orbital transition contribution or were characterized by a lack of metal contribution …”

“…Absorption spectra were obtained in water as vertical electronic excitations on the ground‐state structures by employing the M06 XC functional. The good performances of M06 in the reproduction of optical properties of Pt and other metal‐containing systems has been widely tested . Spin–orbit matrix elements were computed by using the QR‐TDDFT approach, as implemented in the Dalton code, at their ground‐state optimized geometries by using the approximate one‐electron spin–orbit operator with scaled nuclear charges .…”

Theoretical Insights into the Switching Off/On of 1O2 Photosensitization in Chemicontrolled Photodynamic Therapy

“…in which is the employed spin–orbit Hamiltonian and n = x , y , z . This protocol was successfully applied to study the photophysical properties of several dyes . The standard redox potential in solution was calculated in acetonitrile by using one of the most popular methods based on the Born–Haber cycle to derive the standard Gibbs free energy ( G ) for the reaction .…”