Spectrofluorometric investigations on the solvent effects on the photocyclization reaction of diclofenac.

The solvent effects on the photochemical conversion rate of the photosensitizing drug diclofenac (DCF) were investigated using steady-state fluorescence spectroscopy. The spectral information obtained for the photochemical reaction of DCF in a set of neat solvents demonstrates that the photoconversion reaction rate of DCF is not only medium polarity dependent but also hydrogen-bonding dependent. The solvent effects were qualitatively and quantitatively assessed employing various solvatochromic models, including multi-parameter linear regression analysis (MLRA). Interestingly, the MLRA results (R = 0.99) revealed that the photoconversion rate increases with increasing solvent polarizability (π*) and H-bond donor capability (α), whereas the rate decreases with increasing hydrogen-bond acceptor capability (ß). However, predominant effect of the solvent acidity compared to basicity and polarizability was observed. A hypothesis rationalizing the effects of H-bonding and medium polarity on DCF photoconversion reaction is presented and discussed.

Experimental and theoretical investigations of the effect of bis-phenylurea-based aliphatic amine derivative as an efficient green corrosion inhibitor for carbon steel in HCl solution.

A novel bis-phenylurea-based aliphatic amine (BPUA) was prepared via a facile synthetic route, and evaluated as a potential green organic corrosion inhibitor for carbon steel in 1.0 M HCl solutions. NMR spectroscopy experiments confirmed the preparation of the targeted structure. The corrosion inhibitory behavior of the prospective green compound was explored experimentally by electrochemical methods and theoretically by DFT-based quantum chemical calculations. Obtained results revealed an outstanding performance of BPUA, with efficiency of 95.1% at the inhibitor concentration of 50 mg L-1 at 25 °C. The novel compound has improved the steel resistivity and noticeably reduced the corrosion rate from 33 to 1.7 mils per year. Furthermore, the adsorption study elucidates that the mechanism of the corrosion inhibition activity obeys Langmuir isotherm with mixed physisorption/chemisorption modes for BPUA derivatives on the steel surface. Calculated Gibb's free energy of the adsorption process ranges from -35 to -37 kJ mol-1. The SEM morphology analysis validates the electrochemical measurements and substantiates the corrosion-inhibiting properties of BPUA. Additionally, the eco-toxicity assessment on human epithelial MCF-10A cells proved the environmental friendliness of the BPUA derivatives. Density functional theory (DFT) calculations correlated the inhibitor's chemical structure with the corresponding inhibitory behavior. Quantum descriptors disclosed the potentiality of BPUA adsorption onto the surface through the heteroatom-based functional groups and aromatic rings.

Combined experimental and computational investigations of the fluorosolvatochromism of chromeno[4,3-b]pyridine derivatives: Effect of the methoxy substitution.

Extensive research has been conducted on the spectral properties of chromeno[4,3-b]pyridine derivatives, owing to their potential applications in sensing, optoelectronic devices, and drug discovery. This study presents a comprehensive investigation into the fluorosolvatochromism of selected chromeno[4,3-b]pyridine derivatives, with a particular emphasis on the impact of methoxy substitution. Three derivatives were synthesized and subjected to spectral analysis: chromeno[4,3-b]pyridine-3-carboxylate (I) as the parent compound, and its 7-methoxy (II) and 8-methoxy (III) substituted derivatives.The UV-Vis absorption spectra of all derivatives exhibited a broad band with a maximum absorption wavelength that remained unaffected by the surrounding medium. However, distinct fluorescence properties were observed among them. Specifically, derivative II displayed notable fluorescence, while derivatives I and III exhibited no fluorescence properties. Furthermore, derivative II exhibited a fluorescence spectrum that is significantly influenced by the polarity of the medium. To investigate the fluorosolvatochromic behavior in depth, we conducted a comprehensive analysis using various neat solvents with different polarities and hydrogen bonding capabilities. The results obtained revealed a significant positive fluorosolvatochromism, with a bathochromic shift in the fluorescence spectrum as the solvent polarity increased. To understand how specific and non-specific interactions between the solute and the solvent affected the fluorosolvatochromism of II, we employed the four empirical scales model of Catalán. The obtained results demonstrated that intramolecular charge transfer played a crucial role in the fluorescence behavior of II. To provide a molecular-level explanation for the experimental spectral properties, we utilized the DFT and TD-DFT/B3LYP/6-31 + G(d) computational methods with the IEFPCM implicit solvation approach. The spectral differences between II and III were rationalized in terms of the frontier molecular orbitals (FMOs: the HOMO and LUMO), where distinct natures were observed among the examined derivatives. This study offers valuable insights into the impact of methoxy substitution on the physical and chemical properties of chromeno[4,3-b]pyridine derivatives, specifically concerning their spectral properties as elucidated by their fluorosolvatochromic behavior.

Computational Study on the Mechanism of the Photouncaging Reaction of Vemurafenib: Toward an Enhanced Photoprotection Approach for Photosensitive Drugs.

The photochemical behavior of the photosensitive first-line anticancer drug vemurafenib (VFB) is of great interest due to the impact of such behavior on its pharmacological activity. In this work, we computationally elucidated the mechanism of the photoinduced release of VFB from the 4,5-dimethoxy-2-nitrobenzene (DMNB) photoprotecting group by employing various density functional theory (DFT)/time-dependent DFT (TD-DFT) approaches. The computational investigations included a comparative assessment of the influence of the position of the photoprotecting group as a substituent on the thermodynamics and kinetics of the photouncaging reactions of two VFB-DMNB prodrugs, namely pyrrole (NP) and sulfonamide (NS). With the aid of the DFT calculations concerning the activation energy barrier (∆G‡), the obtained results suggest that the step of the photoinduced intramolecular proton transfer of the DMNB moiety is not detrimental concerning the overall reaction profile of the photouncaging reaction of both prodrugs. However, the obtained results suggested that the position of the substitution position of the DMNB photoprotecting group within the prodrug structure has a substantial impact on the photouncaging reaction. In particular, the DMNB-Ns-VFB prodrug exhibited a notable increase in ∆G‡ for the key step of ring opining within the DMNB moiety indicative of potentially hindered kinetics of the photouncaging process compared with DMNB-Np-VFB. Such an increase in ∆G‡ may be attributed to the electronic influence of the NP fragment of the prodrug. The results reported herein elaborate on the mechanism of the photoinduced release of an important anticancer drug from photoprotecting groups with the aim of enhancing our understanding of the photochemical behavior of such photosensitive pharmaceutical materials at the molecular level.

Computational Insights on the Electrocatalytic Behavior of [Cp*Rh] Molecular Catalysts Immobilized on Graphene for Heterogeneous Hydrogen Evolution Reaction.

The heterogeneous metal-based molecular electrocatalyst can typically exhibit attractive features compared to its homogeneous analogue including recoverability and durability. As such, it is necessary to evaluate the electrocatalytic behavior of heterogenized molecular catalysts of interest toward gaining insights concerning the retainability of such behaviors while benefiting from heterogenization. In this work, we examined computationally the electrochemical properties of nanographene-based heterogenized molecular complexes of Rhodium. We assessed, as well, the electrocatalytic behavior of the heterogenized molecular catalyst for hydrogen evolution reaction (HER). Two electrochemical pathways were examined, namely one- and two-electron electrochemical reduction pathways. Interestingly, it is computationally demonstrated that [RhIII(Cp*)(phen)Cl]+-Gr can exhibit redox and electrocatalytic properties for HER that are comparable to its homogeneous analogue via a two-electron reduction pathway. On the other hand, the one-electron reduction pathway is notably found to be less favorable kinetically and thermodynamically. Furthermore, molecular insights are provided with respect to the HER employing molecular orbitals analyses and mechanistic aspects. Importantly, our findings may provide insights toward designing more efficient graphene-based molecular heterogeneous electrocatalysts for more efficient energy production.

On the encapsulation of Olsalazine by ß-cyclodextrin: A DFT-based computational and spectroscopic investigations.

In this work, the supramolecular host-guest interaction of the prodrug Olsalazine (OLZ) and ß-Cyclodextrin (ß-CD) was examined experimentally and computationally. Experimentally, employing the UV-Vis spectroscopic method in aqueous media at various pH's, results obtained using the Benesi-Hilderbrand approach demonstrated that OLZ can form supramolecular inclusion complex with ß-CD with stoichiometric ratio of 1:1. Furthermore, these results revealed that the formation of OLZ: ß-CD complexes exhibited insignificant pH dependency in the range 5-8 with an average binding constant (Kb) of approximately 1×103M-1. Computationally, geometry optimization of 1:1 OLZ: ß-CD complexes was performed employing the ONIOM (DFT((ωB97XB)/6-31+G(d)),SQM(PM3)) approach. Obtained results demonstrated that OLZ: ß-CD complex is stabilized by the formation of intermolecular hydrogen bonds with an average length of approximately 1.8Å. Additionally, the stability of OLZ: ß-CD complex was demonstrated employing ADMP molecular dynamic simulations over a timeframe of 500fs. The molecularity of the supramolecular host-guest interaction between OLZ and ß-CD is presented and interpreted in the essence of TD-DFT and molecular orbitals analyses.

Probing the Solute-Solvent Interaction of an Azo-Bonded Prodrug in Neat and Binary Media: Combined Experimental and Computational Study.

Preferential solvation has significant importance in interpreting the molecular physicochemical properties of wide spectrum of materials in solution. In this work, the solute-solvent interaction of pro-drug Sulfasalazine (SSZ) in neat and binary media was investigated experimentally and computationally. The solute-solvent interactions of interest were spectrophotometrically probed and computationally investigated for providing insights concerning the molecular aspects of SSZ:media interaction. Experimentally, the obtained results in 1,4-dioxane:water binary mixture demonstrated a dramatic non-linear changes in the spectral behavior of SSZ indicative of the dependency of its molecular behaviors on the compositions of the molecular microenvironment in the essence of solute-solvent interaction. Computationally, geometry optimization and simulation of the absorption spectra of SSZ in media of interest were performed employing DFT and TD-DFT methods, respectively, where the solvent effects on the absorption were examined implicitly using IEFPCM method. Obtained results revealed a nonpolar nature of the molecular orbitals that are directly involved in the SSZ:medium interaction. As in good correspondence with the experimental results, these simulations demonstrated that these orbitals are of non-polar nature and hence minimally affected by polarity of the media and in turn favoring the non-polar molecular environments. On the other hand, the molecular origin of SSZ:media interaction was demonstrated explicitly through complexation of SSZ with water molecules revealing a cooperative hydrogen bonding stabilization with an average length of 1.90 Å. The findings of this work demonstrate the significance of the preferential solvation and composition of the molecular microenvironment on the physicochemical properties of molecules of pharmaceutical importance.

Computational exploration of the effect of molecular medium on the tautomerization of azo prodrug of 5-aminosalicylic acid.

The characterization of potential tautomerization of pharmaceutical materials has significant importance. Sulfasalazine (SSZ) is a prodrug that bears 5-aminosalicylic acid and pyridylamino-sulfonyl-phenyl moieties bridged by the azo group. SSZ may be present in various tautomeric forms, where dual tautomerization may occur; namely, amide↔imide and azo↔hydrazone tautomerization through the pyridylamino-sulfonyl-phenyl and salicylic acid moieties, respectively. In this report, we describe the prospects of the effect of molecular medium on the tautomerization of SSZ using selected computational methods. Two approaches were deliberated; namely, the explicit intermolecular hydrogen bonding (HB) through complexation with dimethylformamide (DMF) and implicit solvent effects. Using the DFT/ωB97XD/6-31G+(d) calculations, we conducted geometry optimization calculations of all possible tautomers of SSZ and their corresponding HB complexes with DMF with stoichiometric ratios (SSZ:DMF) of 1:1 and 1:2. The stability of the SSZ tautomeric forms and their corresponding H-Bonded DMF complexes were examined employing the ADMP molecular dynamics approach. Obtained results demonstrate that the amide and azo tautomers are favored over imide and hydrazone in the gas phase with Etaut of 8.3 and 12.8 kcal/mol, respectively. However, these preferences were significantly affected by the implicit solvation effect of water with ΔE of 0.5 and 3.1 kcal mol-1, respectively. Obtained results demonstrate as well that DMF can bind to various sites of SSZ tautomers through intermolecular HBs with length in the range of 1.76-2.39 Å. This in turn demonstrates that intramolecular and intermolecular HB could not only play a significant role in directing the favored tautomeric forms of SSZ, but also distorting the planarity of the molecular comprising the azo and phenyl groups of the SSZ molecule. The ADMP-MD results verified that these complexes and the corresponding intra- and intermolecular HBs are stable over a timeframe of 100 femtosecond. The NBO analysis of the optimized geometries revealed that SSZ:DMF complexes can be stabilized by strong intermolecular HB, as indicated by the second perturbation energy of interaction (E(2)intr). Moreover, these results showed that the intermolecular HB of SSZ:DMF complexes has a notable effect on reducing the strength of intramolecular HB of certain tautomeric forms of SSZ and hence promotes the preference of SSZ toward a specific tautomeric form.

Computational insights into the photocyclization of diclofenac in solution: effects of halogen and hydrogen bonding.

The effects of noncovalent interactions, namely halogen and hydrogen bonding, on the photochemical conversion of the photosensitizing drug diclofenac (DCF) in solution were investigated computationally. Both explicit and implicit solvent effects were qualitatively and quantitatively assessed employing the DFT/6-31+G(d) and SQM(PM7) levels of theory. Full geometry optimizations were performed in solution for the reactant DCF, hypothesized radical-based intermediates, and the main product at both levels of theories. Notably, in good agreement with previous experimental results concerning the intermolecular halogen bonding of DCF, the SQM(PM7) method revealed different values for d(ClO, Å) and ∠(C-ClO, °) for the two chlorine-substituents of DCF, with values of 2.63 Å/162° and 3.13 Å/142° for the trans and cis orientations, respectively. Employing the DFT/6-31+G(d) method with implicit solvent effects was not conclusive; however, explicit solvent effects confirmed the key contribution of hydrogen and halogen bonding in stabilizing/destabilizing the reactant and hypothesized intermediates. Interestingly, the obtained results revealed that a protic solvent such as water can increase the rate of photocyclization of DCF not only through hydrogen bonding effects, but also through halogen bonding. Furthermore, the atomic charges of atoms majorly involved in the photocyclization of DCF were calculated using different methods, namely Mulliken, Hirshfeld, and natural bond orbital (NBO). The obtained results revealed that in all cases there is a notable nonequivalency in the noncovalent intermolecular interactions of the two chlorine substituents of DCF and the radical intermediates with the solvent, which in turn may account for the discrepancy of their reactivity in different media. These computational results provide insight into the importance of halogen and hydrogen bonding throughout the progression of the photochemical conversion of DCF in solution.

Synchronous spectrofluorimetric study of the supramolecular host-guest interaction of ß-cyclodextrin with propranolol: A comparative study.

The objective of this work is to assess the use of constant-wavelength synchronous fluorescence spectroscopy (SFS) in comparison to conventional fluorescence spectroscopy (CFS) for the investigation of the supramolecular host-guest interaction of ß-CD with propranolol (PPL) in aqueous solutions. Scanning for the optimal Δλ at which the SFS can be performed in the presence of ß-CD was examined. The results obtained revealed three distinguishable shapes for PPL using SFS that can be represented by three different Δλ values, namely 10, 40, and 100 nm. However, the effect of the ß-CD concentration on the fluorescence intensity of PPL was examined using CFS and SFS of PPL at a Δλ of 10 and 100 nm. The change in the fluorescence intensity was used to calculate the equilibrium constant (Keq) for the formation of the ß-CD:PPL inclusion complex by applying the Benesi-Hildebrand method. Keq values of 108, 112, and 117 M(-1) were obtained using SFS with a Δλ of 10 and 100 nm, and CFS, respectively. Further, the SFS method was successfully employed to examine the iodide quenching effect on the fluorescence intensity of PPL, where the results obtained revealed a Stern-Volmer quenching constant of 42.8 M(-1), which is in good agreement with results obtained using CFS. All results obtained using the SFS method were compared with the results obtained using the CFS method.

The solvatochromic, spectral, and geometrical properties of nifenazone: a DFT/TD-DFT and experimental study.

The solvatochromic, spectral, and geometrical properties of nifenazone (NIF), a pyrazole-nicotinamide drug, were experimentally and computationally investigated in several neat solvents and in hydro-organic binary systems such as water-acetonitrile and water-dioxane systems. The bathochromic spectral shift observed in NIF absorption spectra when reducing the polarity of the solvent was correlated with the orientation polarizability (Δf). Unlike aprotic solvents, a satisfactory correlation between λ(max) and Δf was determined (linear correlation of regression coefficient, R, equal to 0.93) for polar protic solvents. In addition, the medium-dependent spectral properties were correlated with the Kamlet-Taft solvatochromic parameters (α, ß, and π*) by applying a multiple linear regression analysis (MLRA). The results obtained from this analysis were then employed to establish MLRA relationships for NIF in order to estimate the spectral shift in different solvents, which in turn exhibited excellent correlation (R > 0.99) with the experimental values of ν(max). Density functional theory (DFT) and time-dependent DFT theory calculations coupled with the integral equation formalism-polarizable continuum model (IEF-PCM) were performed to investigate the solvent-dependent spectral and geometrical properties of NIF. The calculations showed good and poor agreements with the experimental results using the CAM-B3LYP and B3LYP functionals, respectively. Experimental and theoretical results confirmed that the chemical properties of NIF are strongly dependent on the polarity of the chosen medium and its hydrogen bonding capability. This in turn supports the hypothesis of the delocalization of the electron density within the pyrazole ring of NIF.

Spectral, thermal, and molecular modeling studies on the encapsulation of selected sulfonamide drugs in ß-cyclodextrin nano-cavity.

In the present work the inclusion complexation of three sulfonamide (SA) drugs, namely sulfisoxazole (SSX), sulfamethizole (SMZ), and Sulfamethazine (STM) with ß-cyclodextrin (ß-CD) has been investigated using UV-Vis spectroscopy, DSC, (1)H NMR spectroscopy, and molecular modeling methods. The binding constant (Kb) of SA:ß-CD inclusion complexation was determined via applying the modified form of Benesi-Hildebrand equation employing the changes in absorbance at λmax. Obtained results revealed that SA drugs form 1:1 inclusion complex with ß-CD with Kb of 650, 1532, 714M(-1) at 25°C for SSX, SMZ, and STM, respectively. The UV-Vis absorption spectra displayed solvatochromic behavior of bathochromic shift with decreasing solvent polarity that in turn is good agreement with their behavior in the presence of ß-CD in terms of environment polarity dependency. The inclusion complex formation between ß-CD and tested SA drugs in liquid and solid states was confirmed by (1)H NMR and DSC, respectively. Using semi-empirical quantum chemistry methods at PM3 theoretical level, inclusion complexes' structures as well as energetic and thermodynamic parameters of encapsulation were elucidated. Obtained results revealed that the encapsulation is favorably energetic and enthalpic in nature with the inclusion of the aniline moiety through the wide rim side of ß-CD nano-cavity. Further, molecular modeling revealed that ß-CD encapsulation of SA drugs reduced their (EHOMO-ELUMO) gap.

On the photophysicochemical properties of selected fluoroquinolones: solvatochromic and fluorescence spectroscopy study.

The photophysicochemical properties of selected fluoroquinolones in different solvents of various physical properties, including polarity and hydrogen bonding ability, were investigated using steady state fluorescence spectroscopy. The solvent-dependant fluorescence emission spectra of selected fluoroquinolones, namely ciprofloxacin (CIPR) and enrofloxacin (ENRO), were employed to gain insights concerning its photophysicochemical properties of interests. Interestingly, fluorescence spectra of the selected drugs exhibited structured emission spectra in nonpolar solvents such as hexane, whereas unstructured spectra were observed in more polar solvents such as alcohols and water. Also, a notable bathochromic shift in λ(max)(em) was observed in fluorescence spectra of both drugs with increasing solvent polarity that resulted in biphasic behavior upon applying the Lippert-Mataga correlation that correspond to general and specific solvent effects. Applying the Lippert-Mataga correlation to the fluorescence spectra of CIPR and ENRO in various solvents was employed to estimate the dipole moment difference between the ground and excited states of them, Δµ(µ(e) - µ(g)), where obtained results revealed the values of 9.4 and 16.2 Debye for the LE and ICT states of ENRO, respectively, and 8.0 and 16.2 Debye for the LE and ICT states of CIPR, respectively. Multiple linear regression analysis (MLRA) based on Kamlet-Taft equating was applied against absorption frequency (ν(abs)), emission frequency (ν(em)), Stokes shift (∆ν), and fluorescence quantum yield (Φ(f)), where obtained results revealed excellent correlation (R: 0.916-0.966) that are consistent with other results considering the effect of solvent polarizability, hydrogen bonding ability, and viscosity on the photophysicochemical properties of the studied fluoroquinolones.

Solvatochromic and fluorescence behavior of sulfisoxazole.

The Fluorescence spectroscopic and solvatochromic behavior of Sulfisoxazole, a sulfa drug with antimicrobial activities, in various pure solvents of different polarity and hydrogen bonding capability is reported. The fluorescence emission spectrum of sulfisoxazole was found to be solvent polarity dependent, where a notable red shift in emission maximum was observed with increasing solvent polarity as well as hydrogen bonding capability. The effects of the latter two solvent parameters were quantitatively investigated using the methods of Lippert-Mataga and solvatochromic comparison method (SCM) that is based on the Kamlet-Taft equation. Particularly, the Lippert-Mataga method was applied to estimate the dipole moment of the excited state (µ(e)) upon plotting Stokes shift versus solvent polarizability (Δf), where a value of 11.54 Debye was obtained. On the other hand, applying the multiple regression analysis to the SCM method revealed that solvent polarizability (π*) and hydrogen-bond donor capability (α) approximately equally stabilize sulfisoxazole in the excited state with minor destabilization contribution by the hydrogen-bond acceptor capability (ß). These findings revealed that the excited state of sulfisoxazole is stabilized by polar solvents, indicating that this drug molecules exhibit larger dipole moment in the excited state than in the ground state, which in turn implies that a potential intramolecular charge transfer (ICT) occurs after excitation.

Integrated microfluidic device for the separation and electrochemical detection of catechol estrogen-derived DNA adducts.

Catechol estrogen-derived DNA adducts are formed as a result of the reaction of catechol estrogen metabolites (e.g., catechol estrogen quinones) with DNA to form depurinating adducts. Developing a new methodology for the detection of various DNA adducts is essential for medical diagnostics, and to this end, we demonstrate the applicability of on-chip capillary electrophoresis with an integrated electrochemical system for the separation and amperometric detection of various catechol estrogen-derived DNA adducts. A hybrid PDMS/glass microchip with in-channel amperometric detection interfaced with in situ palladium decoupler is utilized and presented. The influence of buffer additives along with the effect of the separation voltage on the resolving power of the microchip is discussed. Calibration plots were constructed in the range 0.4-10 µM with r(2) ≥ 0.999, and detection limits in the attomole range are reported. These results suggest that on-chip analysis is applicable for analyzing various DNA adducts as potential biomarkers for future medical diagnostics.