Application of a definitive screening design for the synthesis of a charge-transfer complex of sparfloxacin with tetracyanoethylene: spectroscopic, thermodynamic, kinetics, and DFT computational studies.

Herein, a spectrochemical approach was adopted to study the charge-transfer (CT) complexation of sparfloxacin (SFX) with tetracyanoethylene (TCNE). In this study, a three-level design of experiments (DOE) involving a definitive screening design (DSD) was implemented. This is the first effort to operate this new category of design to determine a pharmaceutical compound in its pure form and in formulations. The proposed design allowed the establishment of a regression model that described the relation between the factorial input and the response surface. Moreover, two charge-transfer states (CTSs) were observed at 390 and 464 nm. The DFT calculations conducted using B3LYP/6-31+G showed that SFX had several donation sites (donor, D), whereas TCNE had two acceptor (A) sites. The two states were influenced differently by the experimental conditions as per the findings of the DSD analysis. In general, the diluting solvent had the largest impact. Probability plots, histograms, individual value plots, residual plots as well as analysis of variance (ANOVA) were delineated at the 95.0% confidence interval (CI). A Job's plot showed that a 1 : 1 complex was formed. The results were further confirmed using Benesi-Hildebrand plots. The proposed approach was proved to be linear in the range of 10-90 µg mL-1 SFX when the absorbance was measured at 464 nm. Different set-ups were adopted for studying the reaction kinetics. Analytical method performance was assessed following the ICH guiding principles, and the results obtained were found to be satisfactory. Complex formation was found to be an exothermic reaction.

Polymeric Micelles of Biodegradable Diblock Copolymers: Enhanced Encapsulation of Hydrophobic Drugs.

Polymeric micelles are potentially efficient in encapsulating and performing the controlled release of various hydrophobic drug molecules. Understanding the fundamental physicochemical properties behind drug⁻polymer systems in terms of interaction strength and compatibility, drug partition coefficient (preferential solubilization), micelle size, morphology, etc., encourages the formulation of polymeric nanocarriers with enhanced drug encapsulating capacity, prolonged circulation time, and stability in the human body. In this review, we systematically address some open issues which are considered to be obstacles inhibiting the commercial availability of polymer-based therapeutics, such as the enhancement of encapsulation capacity by finding better drug⁻polymer compatibility, the drug-release kinetics and mechanisms under chemical and mechanical conditions simulating to physiological conditions, and the role of preparation methods and solvents on the overall performance of micelles.

Photoinduced electron transfer interaction of anthraquinones with aniline quenchers: Influence of methyl substitution in aniline donors.

Photoinduced electron transfer between triplet state of 9,10-anthraquinone (AQ) and its two derivatives: 2-chloro-9,10-anthraquinone (CAQ) and sodium anthraquinone-2-sulfonate (AQS) and ground state aniline (AN) and its dimethyl substitutions: 2,3-dimethylaniline (2,3-DMA), 2,6-dimethylaniline (2,6-DMA), 3,5-dimethylaniline (3,5-DMA) and N,N-dimethylaniline (N,N-DMA) is studied using nanosecond laser flash photolysis at room temperature. Detection of radical bands of quinone anions and aniline cations along with their formation and/or decay kinetics are used to confirm the electron transfer (ET) process. In MeCN medium, AN quenches the triplet state of CAQ (CAQT) but not the triplets AQT or AQST. However in aqueous medium, AN quenches AQST and forms radical ion pair. All the DMAs can react through ET with all the triplet quinones at different degrees of efficiency in MeCN medium. Noticeably, the ring substituted DMAs are less efficient in electron donation to AQT or AQST while the N,N-DMA shows high efficiency in donating electron to all triplet quinones in MeCN medium. Charge distribution of donor molecules, in MeCN medium is calculated using density functional theory (DFT), and shows an enhancement of electron density of the ring of N,N-DMA, making it an ideal electron donor for ET studies compared to other DMAs. This systematic selection and usage of anilines with electrochemically tunable quinones can be viewed as a working model of donor-acceptor system that can be utilized in photoinduced ET applications.

Ab initio study on the formation of triiodide CT complex from the reaction of iodine with 2,3-diaminopyridine.

The charge transfer (CT) interaction between iodine and 2,3-diaminopyridine (DAPY) has been thoroughly investigated via theoretical calculations. A Hartree-Fock, 3-21G level of theory was used to optimize and calculate the Mullican charge distribution scheme as well as the vibrational frequencies of DAPY alone and both its CT complexes with one and two iodine molecules. A very good agreement was found between experiment and theory. New illustrations were concluded with a deep analysis and description for the vibrational frequencies of the formed CT complexes. The two-step CT complex formation mechanism published earlier was supported.

Solvent and linker influences on AQ(*-)/dA(*+) charge-transfer state energetics and dynamics in anthraquinonyl-linker-deoxyadenosine conjugates.

The goal of this work is to produce high yields of long-lived AQ(*-)/dA(*+) charge transfer (CT) excited states (or photoproducts). This goal fits within a larger context of trying generally to produce high yields of long-lived CT excited states within DNA nucleoside conjugates that can be incorporated into DNA duplexes. Depending upon the energetics of the anthraquinonyl (AQ) (3)(pi,pi) state as well as the reduction potentials of the subunits in particular anthraquinonyl-adenine conjugates, CT quenching of the AQ (3)(pi,pi*) state may or may not occur in polar organic solvents. In MeOH, bis(3',5'-O-acetyl)-N(6)-(anthraquinone-2-carbonyl)-2'-deoxyadenosine (AQCOdA) behaves as intended and forms a (3)(AQ(*-)/dA(*+)) CT state with a lifetime of 3 ns. However, in nonpolar THF the AQ(*-)/dA(*+) CT states of AQCOdA are too high in energy to be formed, and in DMSO a (1)(AQ(*-)/dA(*+)) CT state is formed but lives only 6 ps. Although the lowest energy excited state for AQCOdA in MeOH is a (3)(AQ(*-)/dA(*+)) CT state, for N(6)-(anthraquinone-2-methylenyl)-2'-deoxyadenosine (AQMedA) in the same solvent it is a (3)(pi,pi*) state. Changing the linking carbonyl in AQCOdA to methylene in AQMedA makes the anthraquinonyl subunit harder to reduce by 166 mV. This raises the energy of the (3)(AQ(*-)/dA(*+)) CT state above that of the (3)(pi,pi*) in AQMedA. The conclusion is that anthraquinonyl-dA conjugates will not have lowest energy AQ(*-)/dA(*+) CT states in polar organic solvents unless the anthraquinonyl subunit is also substituted with an electron-withdrawing group that raises the AQ-subunit's reduction potential above that of AQ. A key finding in this work is that the lifetime of the (3)(AQ(*-)/dA(*+)) CT excited state (ca. 3 ns) is ca. 500-times longer than that of the corresponding (1)(AQ(*-)/dA(*+)) CT excited state (ca. 6 ps).'

Comparison of Py*+/dU*- charge transfer state dynamics in 5-(1-pyrenyl)-2'-deoxyuridine nucleoside conjugates with amido-, ethylenyl-, and ethynyl linkers.

Femtosecond, picosecond, and nanosecond transient absorbance (TA) and picosecond emission kinetics results are presented for three 5-(1-pyrenyl)-2'-deoxyuridine nucleosides each with a different two-atom linker joining pyrenyl C-1 to uracil C-5. The linkers are respectively -NHCO-, -(CH(2))(2)-, and -C[triple bond]C- for PAdU, PEdU, and PYdU. For all three nucleoside conjugates, most conformers undergo intramolecular charge transfer (CT) from their pyrenyl (1)(pi,pi) excited states to form Py(*+)/dU(*-) CT products in ultrashort times: