Solvent quality changes the structure of G8 PAMAM dendrimer, a disagreement with some experimental interpretations

We have performed approximately 20-40 ns of molecular dynamics (MD) simulations for the generation 8 PAMAM dendrimer in explicit water under varying pH conditions to study the structure of the dendrimer (approximately 156,738 atoms at low pH). This is the first report of such a long MD simulation of a larger generation PAMAM dendrimer including the effect of salt and counterions with explicit water molecules. We find that changing the pH from a high value (approximately 12) to a low value (approximately 3) changes the radius of gyration from Rg = 37.8 to 43.1 A (increasing by 13%). We also find significant back-folding of the primary amines and a large amount of water penetration inside the polymer. The increase in size with decrease in pH is consistent with our earlier studies on G3-G6 and agrees with the Monte Carlo theory by Welch and Muthukumar of G8 (Macromolecules, 1998, 31, 5892) and the experiments on G5 and G8 PAMAM dendrimer by Topp et al. (Macromolecules, 1999, 32, 7232). However, these results disagree dramatically with the interpretations of SANS experiments of G8 PAMAM dendrimers by Nisato et al. (Macromolecules, 2000, 33, 4172) who observe no change in the size of the dendrimer with variations of solution pH and ionic strength. We assume that the disagreement might arise from neglecting nonspherical shape, penetration of water and ions into the core, and aggregation, all of which might depend on pH.     

Food chain model with optimal harvesting in fuzzy environment

A multispecies harvesting model with mutual interactions is formulated based on Lotka–Voltera model with three competing species which are affected not only by harvesting but also by the presence of prey, predator and the third species, which is super predator. In order to understand the dynamics of the system, it is assumed that the super predator follows the logistic growth. Further, there is demand for all the above three species in the market and hence harvesting of all species is performed. We derive the condition for global stability of the system using a suitable Lyapunov function. The possibility of existence of bioeconomic equilibrium is discussed. The optimal harvest policy is studied and the solution is derived under imprecise inflation in fuzzy environment using Pontryagin’s maximal principle. Finally some numerical examples are discussed to illustrate the model.     

The chemical nature of the 2'-substituent in the pentose-sugar dictates the pseudoaromatic character of the nucleobase (pKa) in DNA/RNA

We here show that the pKa (error limit: 0.01 to 0.03 pKa unit) of a nucleobase in a nucleotide can be modulated by the chemical nature of the 2'-substituent at the sugar moiety. This has been evidenced by the measurement of nucleobase pKa in 47 different model nucleoside 3',5'-bis- and 3'-mono-ethylphosphates. The fact that the electronic character of each of the 2'-substituents (Fig. 1) alters the chemical shift of the H2' sugar proton, and also alters the pKa of the nucleobase in the nucleotides has been evidenced by a correlation plot of pKa of N3 of pyrimidine (T/C/U) or pKa of N7 of 9-guaninyl with the corresponding deltaH2' chemical shifts at the neutral pH, which shows linear correlation with high Pearson's correlation coefficients (R = 0.85-0.97). That this modulation of the pKa of the nucleobase by a 2'-substituent is a through-bond as well as through-space effect has been proven by ab initio determined pKa estimation. Interestingly, experimental pKas of nucleobases from NMR titration and the calculated pKas (by ab initio calculations utilizing closed shell HF 6-31G** basis set) are linearly correlated with R = 0.98. It has also been observed that the difference of ground and protonated/de-protonated HOMO orbital energies (DeltaHOMO, a.u.) for the nucleobases (A/G/C/T/U) are well correlated with their pK(a)s in different 2'-substituted 3',5'-bis-ethylphosphate analogs suggesting that only the orbital energy of HOMO can be successfully used to predict the modulation of the chemical reactivity of the nucleobase by the 2'-substituent. It has also been demonstrated that pKa values of nucleobases in 3',5'-bis-ethylphosphates (Table 1) are well correlated with the change in dipole moment for the respective nucleobases after protonation or de-protonation. This work thus unambiguously shows that alteration of the thermodynamic stability (Tm) of the donor-acceptor complexes [ref. 20], as found with various 2'-modified duplexes in the antisense, siRNA or in triplexes by many workers in the field, is a result of alteration of the pseudoaromatic character of the nucleobases engineered by alteration of the chemical nature of the 2'-substitution.     

Characterization of the tryptophan residues of human placental ribonuclease inhibitor and its complex with bovine pancreatic ribonuclease A by steady-state and time-resolved emission spectroscopy

Human placental ribonuclease inhibitor (hRI) containing six tryptophan (Trp) residues located at positions 19, 261, 263, 318, 375, and 438 and its complex with RNase A have been studied using steady-state and time-resolved fluorescence (298 K) as well as low-temperature phosphorescence (77 K). Two Trp residues in wild-type hRI and also in the protein-protein complex with RNase A are resolved optically. The accessible surface area values of Trp residues in the wild-type hRI and its complex and consideration of inter-Trp energy transfer in the wild-type hRI reveal that one of the Trp residues is Trp19, which is located in a hydrophobic buried region. The other Trp residue is tentatively assigned as Trp375 based on experimental results on wild-type hRI and its complex. This residue in the wild-type hRI is more or less solvent exposed. Both the Trp residues are perturbed slightly on complex formation. Trp19 moves slightly toward a more hydrophobic region, and the environment of Trp375 becomes less solvent exposed. The complex formation also results in a more heterogeneous environment for both the optically resolved Trp residues.     

Structural,optical and photoelectron spectroscopic studies of nano/micro ZnO:Cd rods synthesized via sol-gel route

Thin films of cadmium doped zinc oxide rod like microstructure have been synthesized by a very simple sol-gel dip coating technique. Sols were prepared from hydrated zinc oxide precursor and 2-methoxyethanol solvent with monoethanolamine as a sol stabilizer. XRD pattern confirmed the hexagonal wurtzite structure of the deposited ZnO films. Surface morphologies of the films have been studied by a scanning electron microscope and an atomic force microscope, which confirmed that the films are composed of densely packed randomly oriented nano/submicron rods with diameter in the range 300–400 nm having various lengths. We proposed a possible growth mechanism for this rodlike structure. X-ray photoelectron spectroscopic study was used to determine the binding energies and the Zn 2p3/2, Cd 3d5 and O 1s peaks in the XPS spectra were located at 1021.08 eV, 404.6 eV and 529.8 eV respectively, which confirmed the Cd doping in ZnO. Cadmium content in the film was estimated both from energy dispersive X-ray analysis and XPS measurement. Band gap energy determined from optical transmittance spectra systematically varied from 3.28 eV to 3.15 eV for 0% to 5.6% of Cd doping. Urbach parameter determined from the band tail of the transmittance spectra showed that it increased with doping percentage and this parameter for a fixed cadmium doping level decreased with increase of temperature.     

Photophysical study of 3-acetyl-4-oxo-6,7-dihydro-12H-indolo[2,3-a]quinolizine in biomimetic reverse micellar nanocavities: a spectroscopic approach

Photophysical properties of 3-acetyl-4-oxo-6,7-dihydro-12H-indolo[2,3-a]quinolizine (AODIQ), a bioactive molecule, has been investigated in well-characterized, monodispersed biomimicking nanocavities formed by sodium bis(2-ethylhexyl)sulfosuccinate (AOT) in heptane using steady-state and picosecond time resolved fluorescence and fluorescence anisotropy. The emission behavior of AODIQ is very much dependent upon the water/surfactant mole ratio (W), i.e., on the water pool size of the reverse micellar core. AODIQ exhibits a sharp decrease in fluorescence anisotropy with increasing W, implying that the overall motional restriction experienced by the molecule is decreased with increased hydration. Some of the depth-dependent relevant fluorescence parameters, namely, fluorescence maxima and fluorescence anisotropy (r), have been monitored for exploiting the distribution and microenvironment around the probe in the reverse micelles. Fluorescence spectral position and fluorescence quenching studies suggest that the probe does not penetrate into the reverse micellar core; rather it binds at the interfacial region. Quantitaive estimates of the micropolarity and microviscosity at the binding sites of the probe molecule have been determined as a function of W.     

Mono- and bivalent ligands bearing mannose 6-phosphate (M6P) surrogates: targeting the M6P/insulin-like growth factor II receptor

[reaction: see text] Mannose 6-phosphate mimics locked into the alpha-configuration and bearing hydrolase-resistant phosphate surrogates were synthesized and evaluated for binding affinity to the mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R). Affinity increases as the phosphate surrogate is varied in the order malonyl ether < malonate < phosphonate. An alkene cross-metathesis approach to sought-after bivalent M6P-bearing ligands is also described. These compounds were designed to map onto biantennary sectors of high-mannose-type oligosaccharides carried by glycoprotein M6P/IGF2R ligands.     

Acyclic diaminocarbene-based Thiele,Chichibabin, and Müller hydrocarbons

Thiele, Chichibabin and Müller hydrocarbons are considered as classical Kekulé diradicaloids. Herein we report the synthesis and characterization of acyclic diaminocarbene (ADC)-based Thiele, Chichibabin, and Müller hydrocarbons. The calculated singlet–triplet energy gaps are ΔE_S–T = −27.96, −3.70, −0.37 kcal mol⁻¹, respectively, and gradually decrease with the increasing length of the π-conjugated spacer (p-phenylene vs. p,p′-biphenylene vs. p,p′′-terphenylene) between the two ADC-scaffolds. In agreement with the calculations, we also experimentally observed the enhancement of paramagnetic diradical character as a function of the length of the π-conjugated spacer. ADC-based Thiele''s hydrocarbon is EPR silent and exhibits very well resolved NMR spectra, whereas ADC-based Müller''s hydrocarbon displays EPR signals and featureless NMR spectra at room temperature. The spacer also has a strong influence on the UV-Vis-NIR spectra of these compounds. Considering that our methodology is modular, these results provide a convenient platform for the synthesis of an electronically modified new class of carbon-centered Kekulé diradicaloids.

We report the synthesis of acyclic diaminocarbene (ADC)-scaffold based Thiele, Chichibabin, and Müller hydrocarbons. Studies support that the singlet-triplet energy gap depends on the π-conjugated spacer between the ADC scaffolds.