Musa I. El-Barghouthi

Water Dynamics in Water/DMSO Binary Mixtures

The dynamics of dimethyl sulfoxide (DMSO)/water solutions with a wide range of water concentrations are studied using polarization selective infrared pump-probe experiments, two-dimensional infrared (2D IR) vibrational echo spectroscopy, optical heterodyne detected optical Kerr effect (OHD-OKE) experiments, and IR absorption spectroscopy. Vibrational population relaxation of the OD stretch of dilute HOD in H(2)O displays two vibrational lifetimes even at very low water concentrations that are associated with water-water and water-DMSO hydrogen bonds. The IR absorption spectra also show characteristics of both water-DMSO and water-water hydrogen bonding. Although two populations are observed, water anisotropy decays (orientational relaxation) exhibit single ensemble behavior, indicative of concerted reorientation involving water and DMSO molecules. OHD-OKE experiments, which measure the orientational relaxation of DMSO, reveal that the DMSO orientational relaxation times are the same as orientational relaxation times found for water over a wide range of water concentrations within experimental error. The fact that the reorientation times of water and DMSO are basically the same shows that the reorientation of water is coupled to the reorientation of DMSO itself. These observations are discussed in terms of a jump reorientation model. Frequency-frequency correlation functions determined from the 2D IR experiments on the OD stretch show both fast and slow spectral diffusion. In analogy to bulk water, the fast component is assigned to very local hydrogen bond fluctuations. The slow component, which is similar to the slow water reorientation time at each water concentration, is associated with global hydrogen bond structural randomization.

Effect of Surface Area, Micropores, Secondary Micropores, and Mesopores Volumes of Activated Carbons on Reactive Dyes Adsorption from Solution

Abstract The ability of six activated carbons to remove the problematic reactive dyes from textile solution was correlated to their physical characteristics. Specific surface area, micro‐, meso‐, and total volume were established using the Braunnaur, Emmet, and Teller (BET) and Dubinin–Radushkevich (D–R) equations. According to the N2 adsorption method, five of the carbons exhibited type I adsorption characteristics with one carbon showing a type III isotherm. Activated carbon Filtrasorb 400 outperformed the carbons under investigation by showing the presence of advanced primary and secondary micropores. A poor linear correlation between carbon surface area and performance was found. Adsorption properties of carbons were better related to their pore volumes. It was found that secondary micropore volume of carbons (0.8 nm < D secondary micropore < 2 nm) has an important role in reactive dyes adsorption.

A Novel Superdisintegrating Agent Made from Physically Modified Chitosan with Silicon Dioxide

Disintegrants and fillers represent important excipients for immediate-release solid dosage forms in many pharmaceutical applications. A new excipient based on the coprecipitation of chitosan and silica has been achieved. The “intimate” physical association between chitosan and silica creates an insoluble, hydrophilic, highly absorbent material, consequently, resulting in superiority in water uptake, water saturation for gelling formation, and compactability among other superdisintegrants. The new excipient has an outstanding functionality that does not primarily depend on water wicking and swelling properties. In fact, it translates it into superior disintegration characteristics with improved powder flow and compaction properties. Thus, the new excipient could act as a superdisintegrant and pharmaceutical filler at the same time. Studies have shown that chitosan–silica delivers superior performance in wet granulation formulations and is the only disintegrant that is effective at all concentrations in tablet formulation.

Novel inclusion complex of ibuprofen tromethamine with cyclodextrins: Physico-chemical characterization

Guest-host interactions of ibuprofen tromethamine salt (Ibu.T) with native and modified cyclodextrins (CyDs) have been investigated using several techniques, namely phase solubility diagrams (PSDs), proton nuclear magnetic resonance ((1)H NMR), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffractometry (XRPD), scanning-electron microscopy (SEM) and molecular mechanics (MM). From the analysis of PSD data (A(L)-type) it is concluded that the anionic tromethamine salt of ibuprofen (pK(a)=4.55) forms 1:1 soluble complexes with all CyDs investigated in buffered water at pH 7.0, while the neutral form of Ibu forms an insoluble complex with beta-CyD (B(S)-type) in buffered water at pH 2.0. Ibu.T has a lower tendency to complex with beta-CyD (K(11)=58 M(-1) at pH 7.0) compared with the neutral Ibu (K(11)=4200 M(-1)) in water. Complex formation of Ibu.T with beta-CyD (DeltaG(o)=-20.4 kJ/mol) is enthalpy driven (DeltaH(o)=-22.9 kJ/mol) and is accompanied by a small unfavorable entropy (DeltaS(o)=-8.4 J/mol K) change. (1)H NMR studies and MM computations revealed that, on complexation, the hydrophobic central benzene ring of Ibu.T and part of the isobutyl group reside within the beta-CyD cavity leaving the peripheral groups (carboxylate, tromethamine and methyl groups) located near the hydroxyl group networks at either rim of beta-CyD. PSD, (1)H NMR, DSC, FT-IR, XRPD, SEM and MM studies confirmed the formation of Ibu.T/beta-CyD inclusion complex in solution and the solid state.

Derivatization of 2-chlorophenol with 4-amino-anti-pyrine: A novel method for improving the selectivity of molecularly imprinted solid phase extraction of 2-chlorophenol from water

Molecularly imprinted polymer (MIP) may not selectively recognize small template of limited number of functional groups, such as 2-chlorophenol (2-CP). In this work, a novel method was proposed to improve the recognition ability of the molecularly imprinted solid phase extraction (MISPE) of 2-CP from environmental waters. This was achieved by derivatization of 2-CP with 4-amino-anti-pyrine (4-AAP) to enlarge its molecular size and add more binding sites. For that purpose, two MISPE methods of 2-CP were developed. In method 1, a polymer imprinted with 2-CP was used as the extracting sorbent but it suffered from low selectivity and high detection limit of 2-CP (7.10 ng L(-1)). In method 2, a polymer imprinted with 4-AAP derivatized 2-CP (2-CP-4-AAP) was used as the extracting sorbent. Prior to loading the water sample it was subjected to a simple derivatization procedure with 4-AAP. Method 2 showed high recognition ability/selectivity towards 2-CP-4-AAP with lower detection limit of 0.05 ng L(-1) for 2-CP-4-AAP. Method 2 was able to detect the presence of 2-CP-4-AAP in unspiked real water samples and almost full spike recovery was achieved.

Adsorption behavior of anionic reactive dyes on H-type activated carbon: Competitive adsorption and desorption studies

Abstract A microporous H‐type activated carbon was shown to be effective for removing anionic reactive dyes from single and binary component solutions. The extent of the dye adsorption from a single‐solute solution was high (0.25–0.42 mmol/g). From the binary dye solutions, the experimental data indicated a high degree of competition for active sites and the obtained adsorption capacities were reduced to 0.10–0.26 mmol/g. Adsorption data from single dye solutions were correlated using the Langmuir, Ferundlich, and Redlich‐Peterson models. Hydrophobic, hydrophobic mechanisms were significant in the adsorption process. Furthermore, the system showed a low extent of desorption.

Structure-activity relationship of novel series of 1,5-disubstituted tetrazoles as cyclooxygenase-2 inhibitors: Design, synthesis, bioassay screening and molecular docking studies.

A novel class of modified 1,5-disubstituted tetrazoles was designed and synthesized, their biological activity as cyclooxygenases inhibitors was screened, and their molecular docking studies were performed. The structural modifications of the first category included the 4-methylsulfonyl phenyl at C-1 of the central moiety and the linkers (-OH, -CH2OH, -CH2CH2OH) with different lengths at the para position of the N-1 phenyl group. For the second category, the 4-methylsulfonyl phenyl group at C-1 was replaced with 4-aminosulfonyl phenyl. While for the third category, a methylene unit was inserted between the C-1 of the tetrazole central ring and the 4-(methylsulfonyl)phenyl group, keeping the same linkers of various extensions at the para position of the N-1 phenyl group. Among the screened compounds, tetrazole 4i showed the best inhibition potency and selectivity values for both COX-2 enzyme (IC50=3μM, SI>67) and COX-1 isoenzyme (IC50>200μM). Compounds 4e, 4h, and 4i, which have the highest inhibition potency toward COX-2 were selected for the molecular docking studies to verify their inhibition and selectivity for COX-2 over COX-1 with their modified structure. The obtained theoretical studies are in agreement with the in vitro bioassay screening results, which supports the importance of the structural modifications for our studied compounds.

Free energy perturbation and MM/PBSA studies on inclusion complexes of some structurally related compounds with β-cyclodextrin

Molecular dynamics (MD) simulations have been conducted to explore time-resolved guest–host interactions involving inclusion complex formation between β-cyclodextrin and organic molecules bearing two peripheral benzene rings in aqueous solution. Moreover, free energy perturbation (FEP) and thermodynamic integration (TI) methods at different simulation times have been employed to estimate the relative free energy of complexation. Also, the less computer-time demanding molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) method was used to estimate the free energy of complexation based on only 1-ns MD simulation. Results showed that both FEP and TI methods were able to reasonably reproduce the experimental thermodynamic quantities. However, long simulation times (e.g. 15 ns) were needed for benzoin mutating to benzanilide (BAN), while moderately shorter times were sufficient for BAN mutating to phenyl benzoate and for benzilic acid mutating to diphenylacetic acid. The results have been discussed in the light of the differences in the chemical structural and conformational features of the guest molecules. In general, it was apparent that the TI method requires less time for convergence of results than the FEP method. However, the less expensive MM/PBSA method proved capable of producing results that are in agreement with those of the more expensive TI and FEP methods.

Inclusion complexation of Itraconazole with β-and 2-hydroxypropyl-β-cyclodextrins in aqueous solutions

The inclusion behavior of Itraconazole (Itra) with β-cyclodextrin (β-CD) and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) was investigated by using phase solubility and molecular mechanics techniques. The effects of pH and temperature on complex stabilit were also explored. The aqueous solubility of Itra was significantly enhanced as CD concentration increased. Itra tends to form 1: 3 complexes with β-and HP-β-CD at pH ≥ 4 and 1: 2 at pH 2. Thermodynamic parameters for Itra/HP-β-CD show that the 1: 1 complex is driven by enthalpy but retarded by entropy changes. In contrast, the formation of 1: 2 and 1: 3 complexes is largely favored by entropy due to higher desolvation induced by total enclosure of Itra with two (or three) favorably interacting CD molecules. The inclusion mode of Itra/β-CD complexes was proved by molecular mechanics technique, which provided a powerful means for understanding inclusion interactions and processes.

Molecular dynamics of nor-Seco-cucurbit[10]uril complexes

Molecular dynamics simulations were carried out to investigate the structure and dynamics of the 1:1 and 1:2 inclusion complexes formed by nor-Seco-cucurbit[10]uril (ns-CB[10]) with 1-adamantanmethylammonium in water. Two and three orientational isomers were considered for 1:1 and 1:2 complexes, respectively. These isomers are identified by the orientation/position of the ammonium group in the guest relative to the flexible and rigid carbonyl portals of the ns-CB[10] host. Results demonstrate that the inclusion of one guest molecule within one cavity in the host induces similar conformational changes in both the occupied and empty cavities. The average structure for each complex shows that the guest molecule is shifted closer to the side that lacks the CH2-bridge in the host, and that the ammonium group of the guest interacts with the oxygens of the host’s portals via ion–dipole interactions with the hydrophobic part of the guest molecule resides in the cavity of the host. Furthermore, the 1:1 complexes are found to interconvert over the time of the simulation. This observation is not found for 1:2 complexes. Finally, MM–PBSA calculations show that 1:2 complexes are significantly more stable than their 1:1 counterparts while two orientations of the 1:2 complexes are more stable than the third.