Using Water as a Design Element in Crystal Engineering. Host-Guest Compounds of Hydrated 3,5-Dihydroxybenzoic Acid

Thirteen host guest compounds of 3,5-dihydroxybenzoic acid (DHBA) have been structurally characterized. Water molecules occupy the peripheries of a hexagonal void, created with DHBA molecules, and act as ``hooks'' to connect the guest molecules with the host-framework via hydrogen bonding. The ``water hook'' is an OH group acting as a donor. Consequently, the guest molecules were chosen so that they contain good hydrogen bond acceptor functionalities. A number of multicomponent hydrates were isolated with stoichiometries (DHBA)(x)(H2O). (guest),. Of these, compounds with the following as guests were obtained as crystals that were good enough for single crystal work: ethyl acetate (EtOAc), diethyl oxalate, dimethyl oxalate, di(n-propyl) oxalate, diethyl malonate, diethyl succinate, chloroacetonitrile, N,N-dimethyl formamide (DMF), acetone, dimethyl sulfoxide (DMSO), 1-propanol, and 2-butanol. From 2-butanol, a hemihydrate, (DHBA)(2)(H2O), was also obtained concomitantly. Further to guest stabilization, water acts as a good mediator of effective crystal packing and also determines the topology of the host framework. En the present series of compounds, the role of water is wide ranging, and it is not easy to classify it specifically as a host or as a guest.

Conserved water-mediated recognition and dynamics of NAD(+) (carboxamide group) to hIMPDH enzyme: water mimic approach toward the design of isoform-selective inhibitor

Inosine monophosphate dehydrogenase (IMPDH) enzyme involves in GMP biosynthesis pathway. Type I hIMPDH is expressed at lower levels in all cells, whereas type II is especially observed in acute myelogenous leukemia, chronic myelogenous leukemia cancer cells, and 10 ns simulation of the IMP-NAD(+) complex structures (PDB ID. 1B3O and 1JCN) have revealed the presence of a few conserved hydrophilic centers near carboxamide group of NAD(+). Three conserved water molecules (W1, W, and W1 `) in di-nucleotide binding pocket of enzyme have played a significant role in the recognition of carboxamide group (of NAD(+)) to D274 and H93 residues. Based on H-bonding interaction of conserved hydrophilic (water molecular) centers within IMP-NAD(+)-enzyme complexes and their recognition to NAD(+), some covalent modification at carboxamide group of di-nucleotide (NAD(+)) has been made by substituting the -CONH(2)group by -CONHNH2 (carboxyl hydrazide group) using water mimic inhibitor design protocol. The modeled structure of modified ligand may, though, be useful for the development of antileukemic agent or it could be act as better inhibitor for hIMPDH-II.

Swarm intelligence-based solver for parameter estimation of laboratory through-diffusion transport of contaminants

Theoretical approaches are of fundamental importance to predict the potential impact of waste disposal facilities on ground water contamination. Appropriate design parameters are generally estimated be fitting theoretical models to data gathered from field monitoring or laboratory experiments. Transient through-diffusion tests are generally conducted in the laboratory to estimate the mass transport parameters of the proposed barrier material. Thes parameters are usually estimated either by approximate eye-fitting calibration or by combining the solution of the direct problem with any available gradient-based techniques. In this work, an automated, gradient-free solver is developed to estimate the mass transport parameters of a transient through-diffusion model. The proposed inverse model uses a particle swarm optimization (PSO) algorithm that is based on the social behavior of animals searching for food sources. The finite difference numerical solution of the forward model is integrated with the PSO algorithm to solve the inverse problem of parameter estimation. The working principle of the new solver is demonstrated and mass transport parameters are estimated from laboratory through-diffusion experimental data. An inverse model based on the standard gradient-based technique is formulated to compare with the proposed solver. A detailed comparative study is carried out between conventional methods and the proposed solver. The present automated technique is found to be very efficient and robust. The mass transport parameters are obtained with great precision.

X-ray Crystallographic Analysis of the Complexes of Enoyl Acyl Carrier Protein Reductase of Plasmodium falciparum with Triclosan Variants to Elucidate the Importance of Different Functional Groups in Enzyme Inhibition

Triclosan, a well-known inhibitor of Enoyl Acyl Carrier Protein Reductase (ENR) from several pathogenic organisms, is a promising lead compound to design effective drugs. We have solved the X-ray crystal structures of Plasmodium falciparum ENR in complex with triclosan variants having different substituted and unsubstituted groups at different key functional locations. The structures revealed that 4 and 2' substituted compounds have more interactions with the protein, cofactor, and solvents when compared with triclosan. New water molecules were found to interact with some of these inhibitors. Substitution at the 2' position of triclosan caused the relocation of a conserved water molecule, leading to an additional hydrogen bond with the inhibitor. This observation can help in conserved water-based inhibitor design. 2' and 4' unsubstituted compounds showed a movement away from the hydrophobic pocket to compensate for the interactions made by the halogen groups of triclosan. This compound also makes additional interactions with the protein and cofactor which compensate for the lost interactions due to the unsubstitution at 2' and 4'. In cell culture, this inhibitor shows less potency, which indicates that the chlorines at 2' and 4' positions increase the ability of the inhibitor to cross multilayered membranes. This knowledge helps us to modify the different functional groups of triclosan to get more potent inhibitors. (C) 2010 IUBMB IUBMB Life, 62(6): 467-476.

Swam Intelligent Based Inverse Model for Laboratory Double Reservoir Diffusion Experiments

Theoretical approaches are of fundamental importance to predict the potential impact of waste disposal facilities on ground water contamination. Appropriate design parameters are, in general, estimated by fitting the theoretical models to a field monitoring or laboratory experimental data. Double-reservoir diffusion (Transient Through-Diffusion) experiments are generally conducted in the laboratory to estimate the mass transport parameters of the proposed barrier material. These design parameters are estimated by manual parameter adjusting techniques (also called eye-fitting) like Pollute. In this work an automated inverse model is developed to estimate the mass transport parameters from transient through-diffusion experimental data. The proposed inverse model uses particle swarm optimization (PSO) algorithm which is based on the social behaviour of animals for finding their food sources. Finite difference numerical solution of the transient through-diffusion mathematical model is integrated with the PSO algorithm to solve the inverse problem of parameter estimation.The working principle of the new solver is demonstrated by estimating mass transport parameters from the published transient through-diffusion experimental data. The estimated values are compared with the values obtained by existing procedure. The present technique is robust and efficient. The mass transport parameters are obtained with a very good precision in less time

Design for sustainability: case of designing an urban household organic waste management system

Beyond product design, if the notion of product `lifecycle design' enforces the consideration of requirements from all the lifecycle phases of products, design for sustainability enforces the consideration of lifecycle design in the context of the lifecycles of other products, processes, institutions and their design. Consequently, sustainability requirements that need to be met by design are very diverse. In this article, we portray the nature of design process to address sustainability requirements. This is done taking an example of designing a urban household organic waste management system that requires less water and reclaims the nutrients.

Exploring use of climate information for optimal design of water resources infrastructure

We conducted surveys of fire and fuels managers at local, regional, and national levels to gain insights into decision processes and information flows in wildfire management. Survey results in the form of fire managers’ decision calendars show how climate information needs vary seasonally, over space, and through the organizational network, and help determine optimal points for introducing climate information and forecasts into decision processes. We identified opportunities to use climate information in fire management, including seasonal to interannual climate forecasts at all organizational levels, to improve the targeting of fuels treatments and prescribed burns, the positioning and movement of initial attack resources, and staffing and budgeting decisions. Longer-term (5–10 years) outlooks also could be useful at the national level in setting budget and research priorities. We discuss these opportunities and examine the kinds of organizational changes that could facilitate effective use of existing climate information and climate forecast capabilities.

Geoinformatics for Urbanisation and Urban Sprawl Pattern Analysis

Urbanisation is the increase in the population of cities in proportion to the region's rural population. Urbanisation in India is very rapid with urban population growing at around 2.3 percent per annum. Urban sprawl refers to the dispersed development along highways or surrounding the city and in rural countryside with implications such as loss of agricultural land, open space and ecologically sensitive habitats. Sprawl is thus a pattern and pace of land use in which the rate of land consumed for urban purposes exceeds the rate of population growth resulting in an inefficient and consumptive use of land and its associated resources. This unprecedented urbanisation trend due to burgeoning population has posed serious challenges to the decision makers in the city planning and management process involving plethora of issues like infrastructure development, traffic congestion, and basic amenities (electricity, water, and sanitation), etc. In this context, to aid the decision makers in following the holistic approaches in the city and urban planning, the pattern, analysis, visualization of urban growth and its impact on natural resources has gained importance. This communication, analyses the urbanisation pattern and trends using temporal remote sensing data based on supervised learning using maximum likelihood estimation of multivariate normal density parameters and Bayesian classification approach. The technique is implemented for Greater Bangalore – one of the fastest growing city in the World, with Landsat data of 1973, 1992 and 2000, IRS LISS-3 data of 1999, 2006 and MODIS data of 2002 and 2007. The study shows that there has been a growth of 466% in urban areas of Greater Bangalore across 35 years (1973 to 2007). The study unravels the pattern of growth in Greater Bangalore and its implication on local climate and also on the natural resources, necessitating appropriate strategies for the sustainable management.

Water treatment potential in relation to phytoplankton dynamics in tropical sewage-fed urban water bodies

Urban water bodies frequently receive untreated sewage and water levels in such water bodies are maintained by daily inputs of sewage. They function as “variable-zone” anaerobic-aerobic lagoons suffering several macrophyte, biotic and abiotic stresses. We have studied two such lakes in Bangalore (Bellandur-360 ha and Varthur-220 ha) to understand whether such an occurrence could be made beneficial (maintaining water levels as well as treatment). Such hypertrophic water body receives sewage at 180-250mg/L and is discharged at 25-80mg/L COD/BOD in different seasons. In an earlier study we reported macrophyte altering the purification function of the water body. In this paper we studied the impact of phytoplankton dynamics and macrophyte cover on the functions such as organic load removal. Algal community analysis, algal biomass, macrophyte cover, water quality, nutrient status was studied seasonally during 2009-2010. Oxygen deficiency and sometimes anoxia, recorded from surface samples resulted in high quantities of NH4+-N (30-40mg/L) and phosphate (0.5-4mg/L)-characteristics of anoxic hypertrophic urban lakes. The productiveness favoured high phytoplanktonic community characterized by small cells (<10μm; Chlorella sp. - highest numbers). The lake could be clearly demarcated into an initial anaerobic zone (40% area), a facultative zone (20%) and an aerobic zone (40%) based on redox values and GIS/bathymetry. During summer the lake is covered by floating macrophytes converting the lake into an anoxic/anaerobic water pool subduing the water purification function as well as aesthetics. When macrophytes are controlled such sewage fed water bodies can be used for treating urban wastewater while also maintaining water sustainability in these semi-arid ecosystems. This paper reports the community dynamics of phytoplankton, their function and competition with macrophytes.

A relational contract for water demand management

For necessary goods like water, under supply constraints, fairness considerations lead to negative externalities. The objective of this paper is to design an infinite horizon contract or relational contract (a type of long-term contract) that ensures self-enforcing (instead of court-enforced) behaviour by the agents to mitigate the externality due to fairness issues. In this contract, the consumer is induced to consume at firm-supply level using the threat of higher fair price for future time periods. The pricing mechanism, computed in this paper, internalizes the externality and is shown to be economically efficient and provides revenue sufficiency.

Urban water supply and management

Population growth and rapid urbanization lead to considerable stress on already depleting water resources. A great challenge for water authorities of urban cities is to supply adequate and reliable safe water to all consumers. In most of the developing countries water scarcity and high demands have led the water authorities to resort to intermittent supplies. Surface and groundwater are the major sources of supply in urban cities. The direct consequences of intermittent supplies and poor sanitation practices are several incidences of water borne diseases posing public health risk. In order to minimize the supply-demand gap and to assure good quality of water, new techniques or models can be helpful to manage the water distribution systems (WDS) in a better way. In the present paper, a review is carried out on the existing urban water supply management methodologies with a way forward for the proper management of the water supply systems.

Remarkable role of positional isomers in the design of sensors for the ratiometric detection of copper and mercury ions in water

Cation sensing properties of the three positional isomers of rhodamine based sensors (1-3) are studied in water. The sensors differ only in the position of pyridine's nitrogen. The chemosensor 1, with pyridine nitrogen at ortho-position, showed a selective colorimetric detection of Cu(II) ions in water, at physiological pH 7.4 and also in medium containing BSA (bovine serum albumin) and blood serum. Notably the compound 2 and 3, with pyridine end located at meta-and para-positions did not show any color change with Cu(II) ions, although both the compounds showed turn-on change both in color and fluorescence with Hg(II) ions specifically. All the probes showed ratiometric changes with the specific metal ions. The changing position of nitrogen also changed the complexation pattern of the sensors with the metal ions. Probe 1 showed 2 : 1 complexation with Cu(II), whereas 2 and 3 showed 1 : 1 complexation with Hg(II) ions. The mechanism investigation showed that the change in color upon addition of metal ions is due to the ring-opening of the spirolactam ring of the probes. Cu(II) interacted with ligand 1 through a three-point interaction mode comprising carbonyl oxygen, amido nitrogen and pyridine nitrogen end. But in case of 2 and 3, Hg2+ only interacted through pyridine nitrogen ends. Quantitative estimation of Cu2+ and Hg2+ in complex biological media such as bovine albumin protein (BSA) and human blood serum were performed using these sensors. Rapid on-site detection as well as discrimination of these toxic ions was demonstrated using easily prepared portable test-strips.

TSpred: a web server for the rational design of temperature-sensitive mutants

Temperature sensitive (Ts) mutants of proteins provide experimentalists with a powerful and reversible way of conditionally expressing genes. The technique has been widely used in determining the role of gene and gene products in several cellular processes. Traditionally, Ts mutants are generated by random mutagenesis and then selected though laborious large-scale screening. Our web server, TSpred (http://mspc.bii.a-star.edu.sg/TSpred/), now enables users to rationally design Ts mutants for their proteins of interest. TSpred uses hydrophobicity and hydrophobic moment, deduced from primary sequence and residue depth, inferred from 3D structures to predict/identify buried hydrophobic residues. Mutating these residues leads to the creation of Ts mutants. Our method has been experimentally validated in 36 positions in six different proteins. It is an attractive proposition for Ts mutant engineering as it proposes a small number of mutations and with high precision. The accompanying web server is simple and intuitive to use and can handle proteins and protein complexes of different sizes.

Reliability Assessment of a Storm Water Drain Network

Most of the cities in India are undergoing rapid development in recent decades, and many rural localities are undergoing transformation to urban hotspots. These developments have associated land use/land cover (LULC) change that effects runoff response from catchments, which is often evident in the form of increase in runoff peaks, volume and velocity in drain network. Often most of the existing storm water drains are in dilapidated stage owing to improper maintenance or inadequate design. The drains are conventionally designed using procedures that are based on some anticipated future conditions. Further, values of parameters/variables associated with design of the network are traditionally considered to be deterministic. However, in reality, the parameters/variables have uncertainty due to natural and/or inherent randomness. There is a need to consider the uncertainties for designing a storm water drain network that can effectively convey the discharge. The present study evaluates performance of an existing storm water drain network in Bangalore, India, through reliability analysis by Advance First Order Second Moment (AFOSM) method. In the reliability analysis, parameters that are considered to be random variables are roughness coefficient, slope and conduit dimensions. Performance of the existing network is evaluated considering three failure modes. The first failure mode occurs when runoff exceeds capacity of the storm water drain network, while the second failure mode occurs when the actual flow velocity in the storm water drain network exceeds the maximum allowable velocity for erosion control, whereas the third failure mode occurs when the minimum flow velocity is less than the minimum allowable velocity for deposition control. In the analysis, runoff generated from subcatchments of the study area and flow velocity in storm water drains are estimated using Storm Water Management Model (SWMM). Results from the study are presented and discussed. The reliability values are low under the three failure modes, indicating a need to redesign several of the conduits to improve their reliability. This study finds use in devising plans for expansion of the Bangalore storm water drain system. (C) 2015 The Authors. Published by Elsevier B.V.