Experimental and Computational Investigations of Carboplatin Supramolecular Complexes

Abstract

Supramolecular systems (macromolecules), such as calix­[n]­arenes (SCn), cyclodextrins (CDs), and cucurbiturils (CBs), are promising vehicles for anticancer drugs. In this work, guest–host complexes of carboplatin, a second-generation platinum-based anticancer drug, and p-4-sulfocalix­[n]­arenes (n = 4 and 6; PS4 and PS6, respectively) were prepared and studied using 1H NMR, UV, Job’s plot analysis, HPLC, and density-functional theory calculations. The experimental and the computational studies suggest the formation of 1:1 complexes between carboplatin and each of PS4 and PS6. The stability constants of the formed complexes were estimated to be 5.3 × 104 M–1 and 9.8 × 104 M–1, which correspond to free energy of complexation of −6.40 and −6.81 kcal mol–1, in the case of PS4 and PS6, respectively. The interaction free energy depends on the different inclusion modes of carboplatin in the host cavities. UV–vis findings and atoms in molecules analysis showed that hydrogen bond interactions stabilize the host–guest complexes without the full inclusion in the host cavity. The in vitro anticancer study revealed that both complexes exhibited stronger anticancer activities against breast adenocarcinoma cells (MCF-7) and lung cancer cells (A-549) compared to free carboplatin, preluding to their potential use in cancer therapy.

Peganum harmala Alkaloids Self-Assembled Supramolecular Nanocapsules with Enhanced Antioxidant and Cytotoxic Activities

“…The previous studies reported the ability of different host molecules to encapsulate anticancer drugs and selectively deliver them to cancer cells with minimal toxic effects on normal cells. 23 , 24 , 45 − 47 , 49 − 51 These results agree with the in vitro release study demonstrating the pH-triggered release of the HARF from the self-assembled H/ p -SC6 nanocapsules. Cancerous cells have an acidic pH of 5.7, normal cells possess a pH of 7.4, whereas late endosomes and lysosomes have pH values of 4.5–5.5.…”

“… 45 , 52 , 53 Additionally, HARF showed increased cytotoxic activities as its encapsulation within the p -SC6 nanocapsules overcame the extract’s hydrophobic nature and improved its bioavailability. 23 , 24 , 46 This study also highlights the importance of using P. harmala seed alkaloid-rich fraction as a possible natural anticancer drug. Harmala alkaloid-rich fraction’s anticancer activity is attributed to the β-carboline alkaloids that inhibit DNA topoisomerases via DNA intercalation and induction of apoptotic pathways.…”

Host-Guest Complexation of Oxaliplatin and Para-Sulfonatocalix[n]Arenes for Potential Use in Cancer Therapy

“…The spectra of the mixtures displayed a noticeable hyperchromic shift, which correlated with increasing the concentrations of oxaliplatin. The hyperchromic shift observed with increasing concentrations of oxaliplatin was investigated using our previously reported methods [31,66]. The zero-order spectra of the prepared mixtures were divided by the spectrum of p-SC4, and the first derivative of the ratio spectra was obtained using a scaling factor of 10 and Δλ = 4 nm [31,66].…”

“…The stoichiometry and the stability constants of the supramolecular complexes were studied using Job's plot (the method of continuous variation) involving the derivative ratio method, using methods described previously [31,[67][68][69]. From Job's plots, it was revealed that the maximum amplitudes were observed at molar fractions of 0.5, indicating a host-guest complex stoichiometry of The hyperchromic shift observed with increasing concentrations of oxaliplatin was investigated using our previously reported methods [31,66]. The zero-order spectra of the prepared mixtures were divided by the spectrum of p-SC4, and the first derivative of the ratio spectra was obtained using a scaling factor of 10 and ∆λ = 4 nm [31,66].…”

“…From Job's plots, it was revealed that the maximum amplitudes were observed at molar fractions of 0.5, indicating a host-guest complex stoichiometry of The hyperchromic shift observed with increasing concentrations of oxaliplatin was investigated using our previously reported methods [31,66]. The zero-order spectra of the prepared mixtures were divided by the spectrum of p-SC4, and the first derivative of the ratio spectra was obtained using a scaling factor of 10 and ∆λ = 4 nm [31,66]. The values of the peak amplitudes of the first derivative of the ratio spectra for the mixtures ( Figure S2) were then obtained at 267 nm.…”