Anomalously enhanced ion transport and uptake in functionalized angstrom-scale two-dimensional channels.

Emulating angstrom-scale dynamics of the highly selective biological ion channels is a challenging task. Recent work on angstrom-scale artificial channels has expanded our understanding of ion transport and uptake mechanisms under confinement. However, the role of chemical environment in such channels is still not well understood. Here, we report the anomalously enhanced transport and uptake of ions under confined MoS2-based channels that are ~five angstroms in size. The ion uptake preference in the MoS2-based channels can be changed by the selection of surface functional groups and ion uptake sequence due to the interplay between kinetic and thermodynamic factors that depend on whether the ions are mixed or not prior to uptake. Our work offers a holistic picture of ion transport in 2D confinement and highlights ion interplay in this regime.

Visible and Red Light-Triggered Anticancer Profile of a Ferrocene-Re(I)-Tricarbonyl Conjugate: Experimental and Theoretical Studies.

We have red-shifted the light absorbance property of a Re(I)-tricarbonyl complex via distant conjugation of a ferrocene moiety and developed a novel complex ReFctp, [Re(Fctp)(CO)3Cl], where Fctp = 4'-ferrocenyl-2,2':6',2″-terpyridine. ReFctp showed green to red light absorption ability and blue emission, indicating its potential for photodynamic therapy (PDT) application. The conjugation of ferrocene introduced ferrocene-based transitions, which lie at a higher wavelength within the PDT therapeutic window. The time-dependent density functional theory and excited state calculations revealed an efficient intersystem crossing for ReFctp, which is helpful for PDT. ReFctp elicited both PDT type I and type II pathways for reactive oxygen species (ROS) generation and facilitated NADH (1,4-dihydro-nicotinamide adenine dinucleotide) oxidation upon exposure to visible light. Importantly, ReFctp showed effective penetration through the layers of clinically relevant 3D multicellular tumor spheroids and localized primarily in mitochondria (Pearson's correlation coefficient, PCC = 0.65) of A549 cancer cells. ReFctp produced more than 20 times higher phototoxicity (IC50 ∼1.5 µM) by inducing ROS generation and altering mitochondrial membrane potential in A549 cancer cells than the nonferrocene analogue Retp, [Re(CO)3(tp)Cl], where tp = 2,2':6',2″-terpyridine. ReFctp induced apoptotic mode of cell death with a notable photocytotoxicity index (PI, PI = IC50dark/IC50light) and selectivity index (SI, SI = normal cell's IC50dark/cancer cell's IC50light) in the range of 25-33.

Green Light-Triggered Photocatalytic Anticancer Activity of Terpyridine-Based Ru(II) Photocatalysts.

The relentless increase in drug resistance of platinum-based chemotherapeutics has opened the scope for other new cancer therapies with novel mechanisms of action (MoA). Recently, photocatalytic cancer therapy, an intrusive catalytic treatment, is receiving significant interest due to its multitargeting cell death mechanism with high selectivity. Here, we report the synthesis and characterization of three photoresponsive Ru(II) complexes, viz., [Ru(ph-tpy)(bpy)Cl]PF6 (Ru1), [Ru(ph-tpy)(phen)Cl]PF6 (Ru2), and [Ru(ph-tpy)(aip)Cl]PF6 (Ru3), where, ph-tpy = 4'-phenyl-2,2':6',2″-terpyridine, bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, and aip = 2-(anthracen-9-yl)-1H-imidazo[4,5-f][1,10] phenanthroline, showing photocatalytic anticancer activity. The X-ray crystal structures of Ru1 and Ru2 revealed a distorted octahedral geometry with a RuN5Cl core. The complexes showed an intense absorption band in the 440-600 nm range corresponding to the metal-to-ligand charge transfer (MLCT) that was further used to achieve the green light-induced photocatalytic anticancer effect. The mitochondria-targeting photostable complex Ru3 induced phototoxicity with IC50 and PI values of ca. 0.7 µM and 88, respectively, under white light irradiation and ca. 1.9 µM and 35 under green light irradiation against HeLa cells. The complexes (Ru1-Ru3) showed negligible dark cytotoxicity toward normal splenocytes (IC50s > 50 µM). The cell death mechanistic study revealed that Ru3 induced ROS-mediated apoptosis in HeLa cells via mitochondrial depolarization under white or green light exposure. Interestingly, Ru3 also acted as a highly potent catalyst for NADH photo-oxidation under green light. This NADH photo-oxidation process also contributed to the photocytotoxicity of the complexes. Overall, Ru3 presented multitargeting synergistic type I and type II photochemotherapeutic effects.

Experimental and theoretical insights into the supercapacitive performance of interconnected WS2 nanosheets.

Transition metal dichalcogenides (TMDs) are fascinating and prodigious considerations in the electrochemical energy storage sector because of their two dimensional chemistry as well as heterogeneous characteristics. Herein, we synthesized interconnected WS2 nanosheets by a hydrothermal method followed by sulphuration at 850 °C in an argon atmosphere. The ultrathin WS2 nanosheet array is endowed with an excellent specific capacitance of 74 F g-1 at the current density of 3 A g-1 up 7000 cycles. Moreover, a symmetric supercapacitor was fabricated using WS2 nanosheets, which provided the admirable high specific capacity of 6.3 F g-1 at 0.05 A g-1 with the energy and power density of 5.6 × 102 mW h kg-1 and 3.6 × 10 5 mW kg-1, respectively. Density functional theory (DFT) simulations revealed the presence of populated energy states near the Fermi level resulting in a high quantum capacitance value, which supports the experimentally achieved high capacitance value. The attained results recommend interconnected WS2 nanosheets as a novel, robust, and low-cost electrode material for supercapacitor energy storage devices.

Trifluoromethylation of 2D Transition Metal Dichalcogenides: A Mild Functionalization and Tunable p-Type Doping Method.

Chemical modification is a powerful strategy for tuning the electronic properties of 2D semiconductors. Here we report the electrophilic trifluoromethylation of 2D WSe2 and MoS2 under mild conditions using the reagent trifluoromethyl thianthrenium triflate (TTT). Chemical characterization and density functional theory calculations reveal that the trifluoromethyl groups bind covalently to surface chalcogen atoms as well as oxygen substitution sites. Trifluoromethylation induces p-type doping in the underlying 2D material, enabling the modulation of charge transport and optical emission properties in WSe2. This work introduces a versatile and efficient method for tailoring the optical and electronic properties of 2D transition metal dichalcogenides.

Triplet States of Cyanostar and Its Anion Complexes.

The design of advanced optical materials based on triplet states requires knowledge of the triplet energies of the molecular building blocks. To this end, we report the triplet energy of cyanostar (CS) macrocycles, which are the key structure-directing units of small-molecule ionic isolation lattices (SMILES) that have emerged as programmable optical materials. Cyanostar is a cyclic pentamer of covalently linked cyanostilbene units that form π-stacked dimers when binding anions as 2:1 complexes. The triplet energies, ET, of the parent cyanostar and its 2:1 complex around PF6- are measured to be 1.96 and 2.02 eV, respectively, using phosphorescence quenching studies at room temperature. The similarity of these triplet energies suggests that anion complexation leaves the triplet energy relatively unchanged. Similar energies (2.0 and 1.98 eV, respectively) were also obtained from phosphorescence spectra of the iodinated form, I-CS, and of complexes formed with PF6- and IO4- recorded at 85 K in an organic glass. Thus, measures of the triplet energies likely reflect geometries close to those of the ground state either directly by triplet energy transfer to the ground state or indirectly by using frozen media to inhibit relaxation. Density functional theory (DFT) and time-dependent DFT were undertaken on a cyanostar analogue, CSH, to examine the triplet state. The triplet excitation localizes on a single olefin whether in the single cyanostar or its π-stacked dimer. Restriction of the geometrical changes by forming either a dimer of macrocycles, (CSH)2, or a complex, (CSH)2·PF6-, reduces the relaxation resulting in an adiabatic energy of the triplet state of 2.0 eV. This structural constraint is also expected for solid-state SMILES materials. The obtained T1 energy of 2.0 eV is a key guide line for the design of SMILES materials for the manipulation of triplet excitons by triplet state engineering in the future.

Reduction of Platinum(IV) Prodrug Hemoglobin Nanoparticles with Deeply Penetrating Ultrasound Radiation for Tumor-Targeted Therapeutically Enhanced Anticancer Therapy.

The development of PtIV prodrugs that are reduced into the therapeutically active PtII species within the tumor microenvironment has received much research interest. In order to provide spatial and temporal control over the treatment, there is a high demand for the development of compounds that could be selectively activated upon irradiation. Despite recent progress, the majority of PtIV complexes are excited with ultraviolet or blue light, limiting the use of such compounds to superficial application. To overcome this limitation, herein, the first example of PtIV prodrug nanoparticles that could be reduced with deeply penetrating ultrasound radiation is reported, enabling the treatment of deep-seated or large tumors. The nanoparticles were found to selectively accumulate inside a mouse colon carcinoma tumor upon intravenous injection and were able to eradicate the tumor upon exposure to ultrasound radiation.

Highly Efficient Ir(III)-Coumarin Photo-Redox Catalyst for Synergetic Multi-Mode Cancer Photo-Therapy.

Four photo-catalysts of the general formula [Ir(CO6/ppy)2 (L)]Cl where CO6=coumarin 6 (Ir1-Ir3), ppy=2-phenylpyridine (Ir4), L=4'-(3,5-di-tert-butylphenyl)-2,2' : 6',2''-terpyridine (Ir1), 4'-(3,5-bis(trifluoromethyl)phenyl)-2,2' : 6',2''-terpyridine (Ir2 and Ir4), and 4-([2,2' : 6',2''-terpyridin]-4'-yl)-N,N-dimethylaniline (Ir3) were synthesized and characterized. These photostable photo-catalysts (Ir1-Ir3) showed strong visible light absorption between 400-550 nm. Upon light irradiation (465 and 525 nm), Ir1-Ir3 generated singlet oxygen and induced rapidly photo-catalytic oxidation of cellular coenzymes NAD(P)H. Ir1-Ir3 showed time-dependent cellular uptake with excellent intracellular retention efficiency. Upon green light irradiation (525 nm), Ir2 provided a much higher photo-index (PI=793) than the clinically used photosensitizer, 5-aminolevulinicacid (5-ALA, PI>30) against HeLa cancer cells. The observed necro-apoptotic anticancer activity of Ir2 was due to the Ir2 triggered photo-induced intracellular redox imbalance (by NAD(P)H oxidation and ROS generation) and change in the mitochondrial membrane potential. Remarkably, Ir2 showed in vivo photo-induced catalytic anticancer activity in mouse models.

Single-Cell Quantification of a Highly Biocompatible Dinuclear Iridium(III) Complex for Photocatalytic Cancer Therapy.

Quantifying the content of metal-based anticancer drugs within single cancer cells remains a challenge. Here, we used single-cell inductively coupled plasma mass spectrometry to study the uptake and retention of mononuclear (Ir1) and dinuclear (Ir2) IrIII photoredox catalysts. This method allowed rapid and precise quantification of the drug in individual cancer cells. Importantly, Ir2 showed a significant synergism but not an additive effect for NAD(P)H photocatalytic oxidation. The lysosome-targeting Ir2 showed low dark toxicity in vitro and in vivo. Ir2 exhibited high photocatalytic therapeutic efficiency at 525 nm with an excellent photo-index in vitro and in tumor-bearing mice model. Interestingly, the photocatalytic anticancer profile of the dinuclear Ir2 was much better than the mononuclear Ir1, indicating for the first time that dinuclear metal-based photocatalysts can be applied for photocatalytic anticancer treatment.

In-vitro and In-vivo Photocatalytic Cancer Therapy with Biocompatible Iridium(III) Photocatalysts.

Photocatalytic anticancer profile of a IrIII photocatalyst (Ir3) with strong light absorption, high turnover frequency, and excellent biocompatibility is reported. Ir3 showed selective photo-cytotoxicity against cisplatin- and sorafenib-resistant cell lines while remaining dormant to normal cell lines in the dark. Ir3 exhibited excellent photo-catalytic oxidation of cellular co-enzyme, the reduced nicotinamide adenine dinucleotide phosphate (NADPH), and amino acids via a single electron transfer mechanism. The photo-induced intracellular redox imbalance and change in mitochondrial membrane potential resulted in necrosis and apoptosis of cancer cells. Importantly, Ir3 exhibited high biocompatibility and photo-catalytic anticancer efficiency as evident from in vivo zebrafish and mouse cancer models. To the best of our knowledge, Ir3 is the first IrIII based photocatalyst with such a high biocompatibility and photocatalytic anticancer therapeutic effect.

Zero-Overlap Fluorophores for Fluorescent Studies at Any Concentration.

Fluorophores are powerful tools for the study of chemistry, biology, and physics. However, fluorescence is severely impaired when concentrations climb above 5 µM as a result of effects like self-absorption and chromatic shifts in the emitted light. Herein, we report the creation of a charge-transfer (CT) fluorophore and the discovery that its emission color seen at low concentrations is unchanged even at 5 mM, some 3 orders of magnitude beyond typical limits. The fluorophore is composed of a triphenylamine-substituted cyanostar macrocycle, and it exhibits a remarkable Stokes shift of 15 000 cm-1 to generate emission at 633 nm. Crucial to the performance of this fluorophore is the observation that its emission spectrum shows near-zero overlap with the absorption band at 325 nm. We propose that reducing the spectral overlap to zero is a key to achieving full fluorescence across all concentrations. The triphenylamine donor and five cyanostilbene acceptor units of the macrocycle generate an emissive CT state. Unlike closely related donor-acceptor control compounds showing dual emission, the cyanostar framework inhibited emission from the second state to create a zero-overlap fluorophore. We demonstrated the use of emission spectroscopy for characterization of host-guest complexation at millimolar concentrations, which are typically the exclusive domain of NMR spectroscopy. The binding of the PF6- anion generates a 2:1 sandwich complex with blue-shifted emission. Distinct from twisted intramolecular charge-transfer (TICT) states, experiment-supported density functional theory shows a 67° twist inside an acceptor unit in the CT state instead of displaying a twist between the donor and acceptor; it is TICT-like. Inspired by the findings, we uncovered similar concentration-independent behavior from a control compound, strongly suggesting this behavior may be latent to other large Stokes-shift fluorophores. We discuss strategies capable of generating zero-overlap fluorophores to enable accurate fluorescence characterization of processes across all practical concentrations.

Multi-state amine sensing by electron transfers in a BODIPY probe.

Amines are ubiquitous in the chemical industry and are present in a wide range of biological processes, motivating the development of amine-sensitive sensors. There are many turn-on amine sensors, however there are no examples of turn-on sensors that utilize the amine's ability to react by single electron transfer (SET). We investigated a new turn-on amine probe with a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) fluorophore. BODIPY fluorescence is first preprogrammed into an off state by internal photoinduced electron transfer (PET) to an electron-deficient quinolinium ring, resulting in fluorescence quenching. At low concentrations of aliphatic amine (0 to 10 mM), this PET pathway is shut down by external SET from the amine to the photoexcited charge-transfer state of the probe and the fluorescence is turned on. At high concentrations of amine (50 mM to 1 M), we observed collisional quenching of the BODIPY fluorescence. The probe is selective for aliphatic amines over aromatic amines, and aliphatic thiols or alcohols. The three molecular processes modulate the BODIPY fluorescence in a multi-mechanistic way with two of them producing a direct response to amine concentrations. The totality of the three molecular processes produced the first example of a multi-state and dose-responsive amine sensor.

Fenton's Reagent Catalyzed Release of Carbon Monooxide from 1,3-Dihydroxy Acetone.

Triose sugar, 1,3-dihydroxy acetone (DHA) on treatment with Fenton's reagent releases CO under physiological conditions. The release of CO has been demonstrated by myoglobin assay and quantum chemical studies. The mechanistic study has been carried out using B3LYP/6-311++G(d,p), M06-2X/6-311++G(d,p) and CCSD(T)//M06-2X/6-311++G(d,p) level of theories in aqueous medium with dielectric constant of 78.39 by employing the polarized continuum model (PCM). The theoretical investigation shows that DHA breaks down completely into 2 equiv of CO, 1 equiv of CO2, and 6 equiv of H2O without formation of toxic metabolites. The activation barriers of some steps are as high as ∼50 kcal mol-1 along with barrierless intermediate steps resulting from highly stabilized intermediates. The quantum tunneling mechanism of proton transfer steps has been confirmed through kinetic isotope effect study. The natural bond orbital analysis is consistent with the proposed mechanism. The present protocol does not require any photoactivation and thus it can serve as a promising alternative to transition metal CO-releasing molecules. The present work can initiate the study of carbohydrates as CO-releasing molecules for therapeutic applications and it could also be useful in generation of CO for laboratory applications.

Quantum Chemical Investigation of Light-Activated Spin State Change in Pyrene Coupled to Oxoverdazyl Radical Center.

Low-spin ground states and low-lying excited states of higher spin were investigated for four pyrene oxoverdazyl monoradicals 1-4 and eight pyrene dioxoverdazyl diradicals 5-12. The ground states for quartet and quintet spin symmetries that are in reality excited states were found in the region of 565-775 nm above the respective electronic ground states. We calculated the "adiabatic" magnetic exchange coupling constant in the electronic ground state of each isolated biradical (5-12) by unrestricted density functional theory. A number of hybrid functionals such as B3LYP, PBE0, M06, and M06-2X were used. We also used range-separated functionals such as LC-ωPBE and ωB97XD to compare their effects on the coupling constant and the relative energy of the high-spin state. Molecular geometries were optimized for the doublet and quartet spin states of every monoradical (1-4), and the broken symmetry and triplet solutions were optimized for every biradical (5-12), by systematically using 6-311G, 6-311G(d,p), and 6-311++G(d,p) basis sets with each functional. The geometry of each quintet diradical (5-12) was optimized using 6-311G basis set. B3LYP produced the best spin values. The excited state (quartet or quintet)-ground state energy difference (ΔE) increases in the presence of para-phenylene connectors. These energy differences were predicted here. The nature of spin coupling and consequently the ground state spin agree with spin alternation rule and the calculated atomic spin population. The adiabatic coupling constants were predicted for the biradicals (5-12) in their electronic ground states. Electron paramagnetic resonance parameters were determined at 6-311++G** level for the ground state and the quartet state of 1 and compared with the available experimental data. Low-lying excited states were found for the radical center (oxoverdazyl), pyrene, molecule 1, and diradical 5 by time-dependent density functional theory (TDDFT) method using B3LYP hybrid, 6-311++G(d,p) basis set, and the molecular geometry in the electronic ground state. Data from these calculations were used to discuss possible mechanisms for the achievement of the high-spin (excited) states in 1 and 5 and to predict a similar outcome for radicals 2-4 and 6-12 upon excitation. A comprehensive mechanism for the first excitation is proposed here. In particular, we show that the initial excitation of 1 involves large contributions from mixed transitions between pyrene and oxoverdazyl moieties, whereas the initial excitation of 5 is basically that of only the pyrene fragment. Subsequent internal conversion and intersystem crossing are likely to lead to the high-spin states of lower energy. Sample spin-flip TDDFT calculations were also done to confirm the energetic location and composition of the quartet state of 1 and the quintet state of 5.

Comparative Study of Sonodynamic and Photoactivated Cancer Therapies with Re(I)-Tricarbonyl Complexes Comprising Phenanthroline Ligands.

Herein, we have compared the effectivity of light-based photoactivated cancer therapy and ultrasound-based sonodynamic therapy with Re(I)-tricarbonyl complexes (Re1-Re3) against cancer cells. The observed photophysical and TD-DFT calculations indicated the potential of Re1-Re3 to act as good anticancer agents under visible light/ultrasound exposure. Re1 did not display any dark- or light- or ultrasound-triggered anticancer activity. However, Re2 and Re3 displayed concentration-dependent anticancer activity upon light and ultrasound exposure. Interestingly, Re3 produced 1O2 and OH• on light/ultrasound exposure. Moreover, Re3 induced NADH photo-oxidation in PBS and produced H2O2. To the best of our knowledge, NADH photo-oxidation has been achieved here with the Re(I) complex for the first time in PBS. Additionally, Re3 released CO upon light/ultrasound exposure. The cell death mechanism revealed that Re3 produced an apoptotic cell death response in HeLa cells via ROS generation. Interestingly, Re3 showed slightly better anticancer activity under light exposure compared to ultrasound exposure.

CuNi sulphidation maximizes MOR activity by expanding the accessibility of active sites!

Sulphidation of a CuNi alloy of Cu : Ni ratio 81 : 19 led to an exponential activity enhancement in the alkaline methanol oxidation reaction (MOR) by four fold due to an order of magnitude increase in the number of active Cu and Ni sites and improved charge transfer properties.

Dinuclear Tridentate Ru(II) Complex with Strong Near-Infrared Light-Triggered Anticancer Activity.

The design of the dinuclear Ru(II) complex (Ru2) with strong near-infrared (NIR) absorption properties has been reported for efficient anticancer phototherapy. Under 700 nm LED light excitation, Ru2 exhibited remarkable synergistic type I/II photosensitization ability and photocatalytic activity toward intracellular biomolecules. Ru2 showed impressive 700 nm light-triggered anticancer activity under normoxia and hypoxia compared with the clinically used photosensitizer Chlorin e6. The mechanistic studies showed that Ru2 induced intracellular redox imbalance and perturbed the energy metabolism and biosynthesis in A549 cancer cells. Overall, this work provides a new strategy for developing efficient metal-based complexes for anticancer phototherapy under NIR light.

Metaphenylene-based nitroxide diradicals: a protocol to calculate intermolecular coupling constant in a one-dimensional chain.

Intramolecular magnetic exchange coupling constants are determined for seven isolated metaphenylene-based dinitroxide diradicals by unrestricted density functional methodology (UDFT) using a number of hybrid functionals such as B3LYP, B3LYP-D3, M06-2X, HSE, and LC-ωPBE. Geometry optimizations for both triplet and broken symmetry solutions are performed with the 6-311G(d,p) basis set for all the molecules. In all cases, B3LYP somewhat overestimates the coupling constant, and M06-2X produces a more realistic value. The range-separated HSE and LC-ωPBE functional yield large deviations from experiment. The nature of spin coupling agrees with the spin alternation rule and the calculated spin densities, in conjunction with the McConnell rule. It can also be explained in terms of the nondisjoint Single Occupied Molecular Orbital effect. Furthermore, it correlates with the calculated NICS(1) isotropic and zz and hyperfine coupling constants. We also put forward a method for the determination of the intramolecular (J) and intermolecular (J') coupling constants from quantum chemical calculations on a one-dimensional chain of weakly bound diradicals. Two expressions are derived for the energies of different spin states in terms of J and J'. Exemplary UDFT computations are done on the N-mers (N = 2-6) of two diradicals for which the crystal coordinates are available. The intramolecular and intermolecular coupling constants are determined from the calculated UDFT energies. These are indeed in general agreement with the measured coupling constants.

Theoretical investigation of photomagnetic properties of oxoverdazyl-substituted pyrenes.

We have investigated the ground state spin of 10 pairs of possible photochromic diradical isomers by quantum chemical methods. Dihydrogen pyrenes and dinitrile pyrenes have been chosen as spacers with radical centers attached at (1,7) and (1,8) locations. Oxoverdazyl has served as a radical center, and both C and N linkages have been investigated. Triplet molecular geometries have been optimized at the UB3LYP/6-311G(d,p) level. Single-point calculations on triplet and broken symmetry states have been performed using the 6-311++G(d,p) basis set. Careful designs have led to the prediction of strongly coupled dihydropyrene (DHP) isomers, and the cyclophenadiene (CPD) isomers have always been found as weakly coupled. The effect of the functional M06-2X has been investigated. Calculated TDDFT spectra have been sufficient to guarantee photochromism of the designed diradicals. It has been estimated that compounds of diradicals with large coupling constants in the DHP form would show a pronounced change in molar susceptibility on photoconversion. This has led us to identify two molecules that can serve as a photomagnetic switch at room temperature.

Density Functional Theory-Guided Photo-Triggered Anticancer Activity of Curcumin-Based Zinc(II) Complexes.

Photodynamic therapy (PDT) has evolved as a new therapeutic modality for cancer treatment with fewer side effects and drug resistance. Curcumin exhibits PDT activity, but its low bioavailability restricts its clinical application. Here, the bioavailability of curcumin was increased by its complex formation with the Zn(II) center. For a structure-activity relationship study, Zn(II)-based complexes (1-3) comprising N^N-based ligands (2,2'-bipyridine in 1 and 2 or 1,10-phenanthroline in 3) and O^O-based ligands (acetylacetone in 1, monoanionic curcumin in 2 and 3) were synthesized and thoroughly characterized. The X-ray structure of the control complex, 1, indicated a square pyramidal shape of the molecules. Photophysical and TD-DFT studies indicated the potential of 2 and 3 as good visible light type-II photosensitizers for PDT. Guided by the TD-DFT studies, the low-energy visible light-triggered singlet oxygen (1O2) generation efficacy of 2 and 3 was explored in solution and in cancer cells. As predicted by the TD-DFT calculations, these complexes produced 1O2 efficiently in the cytosol of MCF-7 cancer cells and ultimately displayed excellent apoptotic anticancer activity in the presence of light. Moreover, the molecular docking investigation showed that complexes 2 and 3 have very good binding affinities with caspase-9 and p-53 proteins and could activate them for cellular apoptosis. Further molecular dynamics simulations confirmed the stability of 3 in the caspase-9 protein binding site.