Molecular assembly at surfaces: progress and challenges.

Molecules provide versatile building blocks, with a vast palette of functionalities and an ability to assemble via supramolecular and covalent bonding to generate remarkably diverse macromolecular systems. This is abundantly displayed by natural systems that have evolved on Earth, which exploit both supramolecular and covalent protocols to create the machinery of life. Importantly, these molecular assemblies deliver functions that are reproducible, adaptable, finessed and responsive. There is now a real need to translate complex molecular systems to surfaces and interfaces in order to engineer 21st century nanotechnology. 'Top-down' and 'bottom-up' approaches, and utilisation of supramolecular and covalent assembly, are currently being used to create a range of molecular architectures and functionalities at surfaces. In parallel, advanced tools developed for interrogating surfaces and interfaces have been deployed to capture the complexities of molecular behaviour at interfaces from the nanoscale to the macroscale, while advances in theoretical modelling are delivering insights into the balance of interactions that determine system behaviour. A few examples are provided here that outline molecular behaviour at surfaces, and the level of complexity that is inherent in such systems.

Chiral segregation driven by a dynamical response of the adsorption footprint to the local adsorption environment: bitartrate on Cu(110).

Local or global ordering of chiral molecules at a surface is a key step in both chiral separation and heterogeneous enantioselective catalysis. Using density functional theory and scanning probe microscopy results, we find that the accepted structural model for the well known bitartrate on Cu(110) chiral system cannot account for the chiral segregation observed. Instead, we show that this strongly bound, chiral adsorbate changes its adsorption footprint in response to the local environment. The flexible adsorption geometry allows bitartrate to form stable homochiral trimer chains in which the central molecule restructures from a rectangular to an oblique footprint, breaking its internal hydrogen bonds in order to form strong intermolecular hydrogen bonds to neighbouring adsorbates. Racemic structures containing mixed enantiomers do not form strong hydrogen bonds, providing the thermodynamic driving force for the chiral separation that is observed experimentally. This result shows the importance of considering the dynamical response of molecular adsorption footprints at the surface in directing chiral assembly and segregation. The ability of strongly-chemisorbed enantiomers to change footprint depending on the local adsorption environment indicates that supramolecular assemblies at surfaces may exhibit more complex dynamical behaviour than hitherto suspected, which, ultimately, could be tailored to lead to environment and stimuli-responsive chiral surfaces.

Simple rules and the emergence of complexity in surface chirality.

Surface chirality arising from self-organized molecular monolayers may manifest both a handedness and footedness, leading to a dual level of chiral expression. Recent advances have determined both levels of chirality at the single-molecule level and, surprisingly, reveal a plethora of chiral orderings. There is yet no clear understanding of why such varied manifestations of interface chirality occur. Here, we show that the ordering of handedness and footedness of amino-acids within (n× 2) assemblies on Cu(110) may be understood on the basis of three simple generic rules from which a variety chiral expressions naturally arise. These rules also provide insights into how enantiomer assembly at surfaces may be tailored to produce required chiral organizations and segregations.

Pattern Formation by Staphylococcus epidermidis via Droplet Evaporation on Micropillars Arrays at a Surface.

We evaluate the effect of epoxy surface structuring on the evaporation of water droplets containing Staphylococcus epidermidis (S. epidermidis). During evaporation, droplets with S. epidermidis cells yield to complex wetting patterns such as the zipping-wetting1-3 and the coffee-stain effects. Depending on the height of the microstructure, the wetting fronts propagate circularly or in a stepwise manner, leading to the formation of octagonal or square-shaped deposition patterns.4,5 We observed that the shape of the dried droplets has considerable influence on the local spatial distribution of S. epidermidis deposited between micropillars. These changes are attributed to an unexplored interplay between the zipping-wetting1 and the coffee-stain6 effects in polygonally shaped droplets containing S. epidermidis. Induced capillary flows during evaporation of S. epidermidis are modeled with polystyrene particles. Bacterial viability measurements for S. epidermidis show high viability of planktonic cells, but low biomass deposition on the microstructured surfaces. Our findings provide insights into design criteria for the development of microstructured surfaces on which bacterial propagation could be controlled, limiting the use of biocides.

Bacterial viability on chemically modified silicon nanowire arrays.

The global threat of antimicrobial resistance is driving an urgent need for novel antimicrobial strategies. Functional surfaces are essential to prevent spreading of infection and reduce surface contamination. In this study we have fabricated and characterized multiscale-functional nanotopographies with three levels of functionalization: (1) nanostructure topography in the form of silicon nanowires, (2) covalent chemical modification with (3-aminopropyl)triethoxysilane, and (3) incorporation of chlorhexidine digluconate. Cell viability assays were carried out on two model microorganisms E. coli and S. aureus over these nanotopographic surfaces. Using SEM we have identified two growth modes producing distinctive multicellular structures, i.e. in plane growth for E. coli and out of plane growth for S. aureus. We have also shown that these chemically modified SiNWs arrays are effective in reducing the number of planktonic and surface-attached microorganisms.

A novel gene THSD7A is associated with obesity.

Body mass index (BMI) is a non-invasive measurement of obesity. It is commonly used for assessing adiposity and obesity-related risk prediction. Genetic differences between ethnic groups are important factors, which contribute to the variation in phenotypic effects. India inhabited by the first out-of-Africa human population and the contemporary Indian populations are admixture of two ancestral populations; ancestral north Indians (ANI) and ancestral south Indians (ASI). Although ANI are related to Europeans, ASI are not related to any group outside Indian-subcontinent. Hence, we expect novel genetic loci associated with BMI. In association analysis, we found eight genic SNPs in extreme of distribution (P⩽3.75 × 10(-5)), of which WWOX has already been reported to be associated with obesity-related traits hence excluded from further study. Interestingly, we observed rs1526538, an intronic SNP of THSD7A; a novel gene significantly associated with obesity (P=2.88 × 10(-5), 8.922 × 10(-6) and 2.504 × 10(-9) in discovery, replication and combined stages, respectively). THSD7A is neural N-glycoprotein, which promotes angiogenesis and it is well known that angiogenesis modulates obesity, adipose metabolism and insulin sensitivity, hence our result find a correlation. This information can be used for drug target, early diagnosis of obesity and treatment.

1D self-assembly of chemisorbed thymine on Cu(110) driven by dispersion forces.

Adsorption of thymine on a defined Cu(110) surface was studied using reflection-absorption infrared spectroscopy (RAIRS), temperature programmed desorption (TPD), and scanning tunnelling microscopy (STM). In addition, density functional theory (DFT) calculations were undertaken in order to further understand the energetics of adsorption and self-assembly. The combination of RAIRS, TPD, and DFT results indicates that an upright, three-point-bonded adsorption configuration is adopted by the deprotonated thymine at room temperature. DFT calculations show that the upright configuration adopted by individual molecules arises as a direct result of strong O-Cu and N-Cu bonds between the molecule and the surface. STM data reveal that this upright thymine motif self-assembles into 1D chains, which are surprisingly oriented along the open-packed [001] direction of the metal surface and orthogonal to the alignment of the functional groups that are normally implicated in H-bonding interactions. DFT modelling of this system reveals that the molecular organisation is actually driven by dispersion interactions, which cause a slight tilt of the molecule and provide the major driving force for assembly into dimers and 1D chains. The relative orientations and distances of neighbouring molecules are amenable for π-π stacking, suggesting that this is an important contributor in the self-assembly process.

Various faces of Hansen's disease.

Leprosy is a chronic granulomatous disease caused by Mycobacterium leproe. Leprosy once considered a taboo is still misdiagnosed and underdiagnosed. In many cases leprosy is treated as common disorders like psoriasis, pyoderma, angioedema, pre vitiligo. Leprosy can present in many diverse ways which can be confused with many treatable and non treatable, infectious and non infectious forms. Leprosy is considered on the verge of elimination. But Leprosy cases are being newly diagnosed day by day. Here we are presenting 4 atypical cases of leprosy which did not seem to have classical presentation but were diagnosed as leprosy when investigated.

Chiral expression from molecular assemblies at metal surfaces: insights from surface science techniques.

This tutorial review summarises the molecular and atomic-level insights on the nature of surface chirality that have recently been obtained from creating molecular monolayers at defined single crystal metal surfaces in ultra-high vacuum (UHV) conditions and studying them by the powerful techniques of surface science. A myriad of chiral expressions are outlined, from the nanoscale descriptions of single adsorbed chiral molecules (0D chirality), to 1D chiral line structures, small 2D chiral cluster formation, and finally, to macroscale 2D organised chiral adlayers. Homochiral self-recognition and diastereomeric chiral recognition events, probed at the single-molecule level, are also presented.

Target gene selectivity of hypoxia-inducible factor-alpha in renal cancer cells is conveyed by post-DNA-binding mechanisms.

Inactivation of the von Hippel-Lindau tumour suppressor in renal cell carcinoma (RCC) leads to failure of proteolytic regulation of the alpha subunits of hypoxia-inducible factor (HIF), constitutive upregulation of the HIF complex, and overexpression of HIF target genes. However, recent studies have indicated that in this setting, upregulation of the closely related HIF-alpha isoforms, HIF-1alpha and HIF-2alpha, have contrasting effects on tumour growth, and activate distinct sets of target genes. To pursue these findings, we sought to elucidate the mechanisms underlying target gene selectivity for HIF-1alpha and HIF-2alpha. Using chromatin immunoprecipitation to probe binding to hypoxia response elements in vivo, and expression of chimaeric molecules bearing reciprocal domain exchanges between HIF-1alpha and HIF-2alpha molecules, we show that selective activation of HIF-alpha target gene expression is not dependent on selective DNA-binding at the target locus, but depends on non-equivalent C-terminal portions of these molecules. Our data indicate that post-DNA binding mechanisms that are dissimilar for HIF-1alpha and HIF-2alpha determine target gene selectivity in RCC cells.

Identification of novel VHL targets that are associated with the development of renal cell carcinoma.

von Hippel-Lindau (VHL) disease is a dominantly inherited family cancer syndrome characterized by the development of retinal and central nervous system haemangioblastomas, renal cell carcinoma (RCC) and phaeochromocytoma. Specific germline VHL mutations may predispose to haemangioblastomas, RCC and phaeochromocytoma to a varying extent. Although dysregulation of the hypoxia-inducible transcription factor-2 and JunB have been linked to the development of RCC and phaeochromocytoma, respectively, the precise basis for genotype-phenotype correlations in VHL disease have not been defined. To gain insights into the pathogenesis of RCC in VHL disease we compared gene expression microarray profiles in a RCC cell line expressing a Type 1 or Type 2B mutant pVHL (RCC-associated) to those of a Type 2A or 2C mutant (not associated with RCC). We identified 19 differentially expressed novel VHL target genes linked to RCC development. Eight targets were studied in detail by quantitative real-time polymerase chain reaction (three downregulated and five upregulated by wild-type VHL) and for six genes the effect of VHL inactivation was mimicked by hypoxia (but hypoxic-induction of smooth muscle alpha-actin 2 was specific for a RCC cell line). The potential role of four RCC-associated VHL target genes was assessed in vitro. NB thymosin beta (TMSNB) and proteinase-activated receptor 2 (PAR2) (both downregulated by wt pVHL) increased cell growth and motility in a RCC cell line, but aldehyde dehydrogenase (ALDH)1 and ALDH7 had no effect. These findings implicate TMSNB and PAR2 candidate oncogenes in the pathogenesis of VHL-associated RCC.

CHx hydrogenation on Co(0001): a density functional theory study.

Hydrogenation is an important process in the Fischer-Tropsch synthesis. In this work, all the elementary steps of the hydrogenation from C to CH4 are studied on both flat and stepped Co(0001) using density functional theory (DFT). We found that (i) CH3 hydrogenation (CH3+H-->CH4) is the most difficult one among all the elementary reactions on both surfaces, possessing barriers of around 1.0 eV; (ii) the other elementary reactions have the barriers below 0.9 eV on the flat and stepped surfaces; (iii) CH2 is the least stable species among all the CHx(x=1-3) species on both surfaces; and (iv) surface restructuring may have little effect on the CHx(x=0-3) hydrogenation. The barriers of each elementary step on both flat and stepped surfaces are similar and energy profiles are also similar. The reason as to why CHx hydrogenation is not structure-sensitive is also discussed.

General insight into CO oxidation: a density functional theory study of the reaction mechanism on platinum oxides.

CO oxidation on PtO2(110) has been studied using density functional theory calculations. Four possible reaction mechanisms were investigated and the most feasible one is the following: (i) the O at the bridge site of PtO2(110) reacts with CO on the coordinatively unsaturated site (CUS) with a negligible barrier; (ii) O2 adsorbs on the bridge site and then interacts with CO on the CUS to form an OO-CO complex; (iii) the bond of O-OCO breaks to produce CO2 with a small barrier (0.01 eV). The CO oxidation mechanisms on metals and metal oxides are rationalized by a simple model: The O-surface bonding determines the reactivity on surfaces; it also determines whether the atomic or molecular mechanism is preferred. The reactivity on metal oxides is further found to be related to the 3rd ionization energy of the metal atom.

Extended surface chirality from supramolecular assemblies of adsorbed chiral molecules

The increasing demand of the chemical and pharmaceutical industries for enantiomerically pure compounds has spurred the development of a range of so-called 'chiral technologies' (ref. 1), which aim to exert the ultimate control over a chemical reaction by directing its enantioselectivity. Heterogeneous enantioselective catalysis is particularly attractive because it allows the production and ready separation of large quantities of chiral product while using only small quantities of catalyst. Heterogeneous enantioselectivity is usually induced by adsorbing chiral molecules onto catalytically active surfaces. A mimic of one such catalyst is formed by adsorbing (R,R)-tartaric acid molecules on Cu(110) surfaces: this generates a variety of surface phases, of which only one is potentially catalytically active, and leaves the question of how adsorbed chiral molecules give rise to enantioselectivity. Here we show that the active phase consists of extended supramolecular assemblies of adsorbed (R,R)-tartaric acid, which destroy existing symmetry elements of the underlying metal and directly bestow chirality to the modified surface. The adsorbed assemblies create chiral 'channels' exposing bare metal atoms, and it is these chiral spaces that we believe to be responsible for imparting enantioselectivity, by forcing the orientation of reactant molecules docking onto catalytically active metal sites. Our findings demonstrate that it is possible to sustain a single chiral domain across an extended surface--provided that reflection domains of opposite handedness are removed by a rigid and chiral local adsorption geometry, and that inequivalent rotation domains are removed by successful matching of the rotational symmetry of the adsorbed molecule with that of the underlying metal surface.

Peutz-Jeghers syndrome: confirmation of linkage to chromosome 19p13.3 and identification of a potential second locus, on 19q13.4.

Peutz-Jeghers syndrome (PJS) is an autosomal dominant disease with variable expression and incomplete penetrance, characterized by mucocutaneous pigmentation and hamartomatous polyposis. Patients with PJS have increased frequency of gastrointestinal and extraintestinal malignancies (ovaries, testes, and breast). In order to map the locus (or loci) associated with PJS, we performed a genomewide linkage analysis, using DNA polymorphisms in six families (two from Spain, two from India, one from the United States, and one from Portugal) comprising a total of 93 individuals, including 39 affected and 48 unaffected individuals and 6 individuals with unknown status. During this study, localization of a PJS gene to 19p13.3 (around marker D19S886) had been reported elsewhere. For our families, marker D19S886 yielded a maximum LOD score of 4.74 at a recombination fraction (theta) of .045; multipoint linkage analysis resulted in a LOD score of 7.51 for the interval between D19S886 and 19 pter. However, markers on 19q13.4 also showed significant evidence for linkage. For example, D19S880 resulted in a maximum LOD score of 3.8 at theta = .13. Most of this positive linkage was contributed by a single family, PJS07. These results confirm the mapping of a common PJS locus on 19p13.3 but also suggest the existence, in a minority of families, of a potential second PJS locus, on 19q13.4. Positional cloning and characterization of the PJS mutations will clarify the genetics of the syndrome and the implication of the gene(s) in the predisposition to neoplasias.

MHC class II alleles and haplotypes in patients with pemphigus vulgaris from India.

Pemphigus vulgaris (PV) is a blistering disease of the skin and mucous membranes characterized by an autoantibody response against a keratinocyte adhesion molecule, desmoglein 3, causing acantholysis and blister formation. We compared high resolution MHC class II alleles and haplotype frequencies (HLA-DRB, DQA1 and DQB1) in 37 patients with PV to 89 haplotypes of normal relatives from New Delhi and Ahmedabad. We found that PV patients had significantly increased frequencies of DRB1*1404 (P < 0.0001), DQA1*0101 (P = 0.001), and DQB1*0503 (P < 0.0001). These associations were due to the increased frequencies of the haplotype HLA-DRB1*1404, DRB3*0202, DQA1*0101, DQB1*0503 in patients compared to control haplotypes (p < 0.0001). Also, patients from Ahmedabad had a significant increase in HLA-DQB1*0302 (p = 0.03). An identical amino acid sequence (Leu-Leu-Glu-Arg-Arg-Arg-Ala-Glu), in positions 67-74 of the beta domain of DRB alleles is restricted to some DR14 alleles. Therefore, there are three possible explanations for class II allele involvement in autoantibody in PV patients with class II haplotypes marked by HLA-DR14. First, the class II alleles could be markers for an unidentified susceptibility gene in linkage disequilibrium with them. Second, the primary association could be with DQB1*0503 and the association with HLA-DR14 alleles would be the result of linkage disequilibrium. Third, the HLA-DRB1 locus susceptibility could involve a specific amino acid sequence in the third hypervariable region shared by several HLA-DR14 alleles.

Monilethrix in pedigree.

A 30-year-old female patient presented with tiny papular scalp lesions with sparse, very short, curly hair of only 8 to 12 mm. Microscopic examination of hair revealed typical beaded or moniliform appearance. She also had typical lesions of psoriasis for past 2 months. Her father, 2 sisters and her 6-year-old daughter had similar types of beaded scalp hair.

Ehlers-Danlos syndrome.

A case of Ehlers-Danlos Syndrome in a 19 years old male involving cutaneous and skeletal systems is reported. A clinical scoring system to diagnose such cases is highlighted.

A comparative study of loratadine versus pheniramine maleate in chronic idiopathic urticaria.

Fifty cases with chronic idiopathic urticaria of more than 3 months duration were selected and divided into two groups. Group 'A' was given 10 mg loratadine once daily, while group 'B' was given pheniramine maleate 25 mg, twice daily for one month. All patients were followed for one month more. 48% excellent response was observed in group 'A' while 16% excellent response was observed in group 'B'. Good response was observed in 24% of patients in group 'A', while in group 'B' 16% of patients had good response. No side effects were observed in loratadine group, while drowsiness was observed in pheniramine group.