Solvent effect in molecular recognition: Determining binding constants in different solvents following an extraction based protocol

Semi-rigid molecular tweezers 1, 3 and 4 bind picric acid with more than tenfold increment in tetrachloromethane as compared to chloroform.

Ruthenium-Oxygen Coordination-Driven Self-Assembly of a Ru-8(II) Incomplete Prism: Synthesis, Structure, and Shape-Selective Molecular Recognition Study

Coordination-driven self-assembly of 1,3,5-benzenetricarboxylate (tma; 1) and oxalato-bridged p-cymeneruthenium(II) building block Ru-2(mu-eta(4)-C2O4)(MeOH)(2)(eta(6)-p-cymene)(2)](O3SCF3)(2) (2) affords an unusual octanuclear incomplete prism Ru-8(eta(6)-p-cymene)(8)(tma)(2)(mu-eta(4)-C2O4)(2)(OMe)(4)](O3SCF3)( 2) (3), which exhibits a remarkable shape-selective binding affinity for neutral phenolic compounds via hydrogen-bonding interactions (p-cymene = p-(PrC6H4Me)-Pr-i). Such a binding was confirmed by single-crystal X-ray diffraction analysis using 1,3,5-trihydroxybenzene as an analyte.

Bile acids in asymmetric synthesis and molecular recognition

This account summarizes the progress made in our laboratory towards the development of new uses of naturally occurring bile acids. Applications in Asymmetric Synthesis (intramolecular coupling, and intermolecular reactions) and Molecular Recognition are described with suitable examples.

Self assembly of bivalent glycolipids on single walled carbon nanotubes and their specific molecular recognition properties

Solubilization of single walled carbon nanotubes (SWNTs) in aqueous milieu by self assembly of bivalent glycolipids is described. Thorough analysis of the resulting composites involving Vis/near-IR spectroscopy, surface plasmon resonance, confocal Raman and atomic force microscopy reveals that glycolipid-coated SWNTs possess specific molecular recognition properties towards lectins.

Thiol cofactors for selenoenzymes and their synthetic mimics

The importance of selenium as an essential trace element is now well recognized. In proteins, the redox-active selenium moiety is incorporated as selenocysteine (Sec), the 21st amino acid. In mammals, selenium exerts its redox activities through several selenocysteine-containing enzymes, which include glutathione peroxidase (GPx), iodothyronine deiodinase (ID), and thioredoxin reductase (TrxR). Although these enzymes have Sec in their active sites, they catalyze completely different reactions and their substrate specificity and cofactor or co-substrate systems are significantly different. The antioxidant enzyme GPx uses the tripeptide glutathione (GSH) for the catalytic reduction of hydrogen peroxide and organic peroxides, whereas the larger and more advanced mammalian TrxRs have cysteine moieties in different subunits and prefer to utilize these internal cysteines as thiol cofactors for their catalytic activity. On the other hand, the nature of in vivo cofactor for the deiodinating enzyme ID is not known, although the use of thiols as reducing agents has been well-documented. Recent studies suggest that molecular recognition and effective binding of the thiol cofactors at the active site of the selenoenzymes and their mimics play crucial roles in the catalytic activity. The aim of this perspective is to present an overview of the thiol cofactor systems used by different selenoenzymes and their mimics.

Unlocking the potential of bile acids in synthesis, supramolecular/materials chemistry and nanoscience

The Maitra group has explored a variety of chemistry with bile acids during the past 15 years and these experiments have covered a wide variety of chemistry - asymmetric synthesis, molecular recognition, ion receptors/sensors, dendrimers, low molecular mass organo and hydrogelators, gel-nanoparticle composites, etc. Some of what excites us in this field is highlighted in this perspective article.

Elucidation of the mechanism of interaction of sheep spleen galectin-1 with splenocytes and its role in cell-matrix adhesion

The binding of a 14 kDa beta-galactoside animal lectin to splenocytes has been studied in detail. The binding data show that there are two classes of binding sites on the cells for the lectin: a high-affinity site with a K-a ranging from 1.1 x 10(6) to 5.1 x 10(5) M-1 and a low affinity binding site with a K-a ranging from 7.7 x 10(4) to 3.4 x 10(4) M-1 The number of receptors per cell for the high- and low-affinity sites is 9 +/- 3 x 10(6) and 2.5 +/- 0.5 x 10(6) respectively. The temperature dependence of the K value yielded the thermodynamic parameters. The energetics of this interaction shows that, although this interaction is essentially enthalpically driven (Delta H - 21 kJ lambda mol(-1)) for the high-affinity sites, there is a very favorable entropy contribution to the free energy of this interaction (-T Delta S - 17.5 Jmol(-1)), suggesting that hydrophobic interaction may also be playing a role in this interaction. Lactose brought about a 20% inhibition of this interaction, whereas the glycoprotein asialofetuin brought about a 75 % inhibition, suggesting that complex carbohydrate structures are involved in the binding of galectin-1 to splenocytes, Galectin-1 also mediated the binding and adhesion of splenocytes to the extracellular matrix glycoprotein laminin, suggesting a role for it in cell-matrix interactions. Copyright (C) 2000 John Wiley & Sons, Ltd.

Supramolecular Chirality in Organogels: A Detailed Spectroscopic, Morphological, and Rheological Investigation of Gels (and Xerogels) Derived from Alkyl Pyrenyl Urethanes

This Article addresses the formation of chiral supramolecular structures in the organogels derived from chiral organogelator 1R (or 2R), and its mixtures with its enantiomer (1S) and achiral analogue 3 by extensive circular dichroism (CD) spectroscopic measurements. Morphological analysis by atomic force microscopy (AFM) and scanning electron microscopy (SEM) were complemented by the measurements of their bulk properties by thermal stability and rheological studies. Specific molecular recognition events (1/3 vs 2/3) and solvent effects (isooctane vs dodecane) were found to be critical in the formation of chiral aggregates. Theoretical studies were also carried out to understand the interactions responsible for the formation of the superstructures.

Structural features of B-DNA dodecamer crystal structures: Influence of crystal packing versus base sequence

We have analyzed the set of inter and intra base pair parameters for each dinucleotide step in single crystal structures of dodecamers, solved at high and medium resolution and all crystallized in P2(1)2(1)2(1) space group. The objective was to identify whether all the structures which have either the Drew-Dickerson (DD) sequence d[CGCGAATTCGCG] with some base modification or related sequence (non-DD), would display the same sequence dependent structural variability about its palindromic sequence, despite the molecule being bent at one end because of similar crystal lattice packing effect. Most of the local doublet parameters for base pairs steps G2-C3 and G10-C11 positions, symmetrically situated about the lateral twofold, were significantly correlated between themselves. In non-DD sequences, significant correlations between these positional parameters were absent. The different range of local step parameter values at each sequence position contributed to the gross feature of smooth helix axis bending in all structures. The base pair parameters in some of the positions, for medium resolution DD sequence, were quite unlike the high-resolution set and encompassed a higher range of values. Twist and slide are the two main parameters that show wider conformational range for the middle region of non-DD sequence structures in comparison to DD sequence structures. On the contrary, the minor and major groove features bear good resemblance between DD and non-DD sequence crystal structure datasets. The sugar-phosphate backbone torsion angles are similar in all structures, in sharp contrast to base pair parameter variation for high and low resolution DD and non-DD sequence structures, consisting of unusual (epsilon =g(-), xi =t) B-II conformation at the 10(th) position of the dodecamer sequence. Thus examining DD and non-DD sequence structures packed in the same crystal lattice arrangement, we infer that inter and intra base pair parameters are as symmetrically equivalent in its value as the symmetry related step for the palindromic DD sequence about lateral two-fold axis. This feature would lead us to agree with the conclusion that DNA conformation is not substantially affected by end-to-end or lateral inter-molecular interaction due to crystal lattice packing effect. Non-DD sequence structures acquire step parameter values which reflect the altered sequence at each of the dodecamer sequence position in the orthorhombic lattice while showing similar gross features of DD sequence structures

Role of organic fluorine in crystal engineering

The design of compounds with novel and improved physico-chemical properties as advanced functional materials with a specific application spectrum requires the knowledge about possible supramolecular packing motifs and their experimental control in crystalline lattice. Besides the structure of the individual molecule, non-covalent interactions play a significant role in the determination of molecular conformation, along with the formation of three-dimensional supramolecular architecture in a crystal as a requirement for molecular recognition processes, and the related bioactivity. Involvement of functional groups will contribute to the formation of a predefined packing motif due to their well-defined interactions. The strength and directionality of these interactions create characteristic packing motifs, which can be used for the design of supramolecular arrangements by the development of appropriate strategies for the precise control of their topology. Most relevant of these non-covalent interactions are stacking interactions and hydrogen bonds, which have been subjects of extensive study in the last two decades. In recent literature, substantial efforts have been put in by various researchers towards the understanding of interactions involving organic fluorine and the role they play in generating different packing motifs which guides assembling of molecules in the crystal lattice.

The structural theory and physical organic chemistry

Woolley's revolutionary proposal that quantum mechanics does not sanction the concept of ''molecular structure'' - which is but only a ''metaphor'' - has fundamental implications for physical organic chemistry. On the one hand, the Uncertainty Principle limits the precision with which transition state structures may be defined; on the other, extension of the structure concept to the transition state may be unviable. Attempts to define transition states have indeed caused controversy. Consequences for molecular recognition, and a mechanistic classification, are also discussed.

Roles of residues in the interface of transient protein-protein complexes before complexation

Transient protein-protein interactions play crucial roles in all facets of cellular physiology. Here, using an analysis on known 3-D structures of transient protein-protein complexes, their corresponding uncomplexed forms and energy calculations we seek to understand the roles of protein-protein interfacial residues in the unbound forms. We show that there are conformationally near invariant and evolutionarily conserved interfacial residues which are rigid and they account for similar to 65% of the core interface. Interestingly, some of these residues contribute significantly to the stabilization of the interface structure in the uncomplexed form. Such residues have strong energetic basis to perform dual roles of stabilizing the structure of the uncomplexed form as well as the complex once formed while they maintain their rigid nature throughout. This feature is evolutionarily well conserved at both the structural and sequence levels. We believe this analysis has general bearing in the prediction of interfaces and understanding molecular recognition.

Probing acid-amide intermolecular hydrogen bonding by NMR spectroscopy and DFT calculations

Benzene carboxylic acids and Benzamide act as their self-complement in molecular recognition to form inter-molecular hydrogen bonded dimers between amide and carboxylic acid groups, which have been investigated by H-1, C-13 and N-15 NMR spectroscopy. Extensive NMR studies using diffusion ordered spectroscopy (DOSY), variable temperature 1D, 2D NMR, established the formation of heterodimers of benzamide with benzoic acid, salicylic acid and phenyl acetic acid in deuterated chloroform solution. Association constants for the complex formation in the solution state have been determined. The results are ascertained by X-ray diffraction in the solid state. Intermolecular interactions in solution and in solid state were found to be similar. The structural parameters obtained by X-ray diffraction studies are compared with those obtained by DFT calculations. (C) 2012 Elsevier B.V. All rights reserved.

Synthesis and structural characterization of some trisulfide analoges of thiouracil-based antithyroid drugs

Thiourea-based antithyroid drugs are effectively used for the treatment of hyperthyroidism. In this paper, we describe the synthesis of new trisulfides (11-12) from the commonly used thiourea-based antithyroid drugs such as 6-n-propyl-2-thiouracil (PTU) and 6-methyl-2-thiouracil (MTU) in the reaction with I-2/KI system. Structural analysis by single crystal X-ray diffraction studies revealed the stabilization of trisulfides by a lactam-lactim tautomerism facilitating effective intramolecular as well as intermolecular non-covalent interactions. Although the structures of both trisulfides were found to be quite similar, a notable difference in the intermolecular interactions was observed between compounds 11 and 12 leading to different structural patterns. Structural stabilization of these trisulfides by tautomerism followed by intramolecular as well as intermolecular H-bonds makes these molecules as perfect examples in molecular recognition with self-complementary donor and acceptor units within a single molecule. (C) 2012 Elsevier B.V. All rights reserved.

A Comparative Kinetic and Thermodynamic Perspective of the sigma-Competition Model in Escherichia coli

Transcription is the most fundamental step in gene expression in any living organism. Various environmental cues help in the maturation of core RNA polymerase (RNAP; alpha(2)beta beta'omega) with different sigma-factors, leading to the directed recruitment of RNAP to different promoter DNA sequences. Thus it is essential to determine the sigma-factors that affect the preferential partitioning of core RNAP among various a-actors, and the role of sigma-switching in transcriptional gene regulation. Further, the macromolecular assembly of holo RNAP takes place in an extremely crowded environment within a cell, and thus far the kinetics and thermodynamics of this molecular recognition process have not been well addressed. In this study we used a site-directed bioaffinity immobilization method to evaluate the relative binding affinities of three different Escherichia coli sigma-factors to the same core RNAP with variations in temperature and ionic strength while emulating the crowded cellular milieu. Our data indicate that the interaction of core RNAP-sigma is susceptible to changes in external stimuli such as osmolytic and thermal stress, and the degree of susceptibility varies among different sigma-factors. This allows for a reversible sigma-switching from housekeeping factors to alternate sigma-factors when the organism senses a change in its physiological conditions.