3,3'-Bis(acylamino)-2,2'-bipyridine discotics : desymmetrization and functionalization

In the field of supramolecular chemistry control over self-assembly is one of the main targets. This might be accomplished by adaptation of the environment of organic assemblies by allowing their interaction with other molecules or substrates. To do so, the assembling component has to be equipped with a functional site, which requires derivatization. Also, derivatization in itself may result in enhanced, beneficial supramolecular behavior. In this thesis, derivatization of disc-shaped molecules at their periphery is described with the goal of introducing functionality into the discotic systems and of allowing the discotics to perform desirable, programmed interactions with other molecules. The discotics are composed of a central trimesic core and radially equipped with three 2,2'-bipyridinyl-3,3'-diamine moieties that in turn are linked to three gallic moieties decorated with peripheral alkyl tails. In Chapter 1 an overview of functionalized and desymmetrized discotics is given, with the focus on single-core discotics like triphenylenes, hexabenzocoronenes, phthalocyanines, porphyrins and benzene-1,3,5-tricarboxamides. The synthesis of the desymmetrized derivatives as well as their enhanced supramolecular and material properties is described. It is clear that desymmetrization and functionalization of the originally symmetrical discotics allows programmed interaction with other molecules or gives rise to functional materials besides the original focus on one-dimensional assembly and columnar liquid crystals. In Chapter 2, two synthetic strategies to replace one of the 3,4,5-trialkoxyphenyl units of bis(acylamino)-2,2'-bipyridine based discotics with a phenyl (disc 1, Figure 1) or 4-pyridyl (disc 2, Figure 1) unit are proposed. The first synthetic strategy is based on a statistical approach and the second one on a step-wise approach involving protective-group chemistry. Both strategies have afforded the desired non-symmetrical discotics but the second strategy has many advantages over the first one, like easier purification steps and accessibility to multigram amounts of the desired discs and their valuable precursors. Importantly, the desymmetrization does not affect significantly the preorganized hydrogen-bonded structure of the discotics. The self-assembly properties of non-symmetrical discotics 1 and 2 are reported in Chapter 3. Both discotics display helical self-assembly in the mesophase and in apolar solution. Importantly, this assembly of discs 2 is similar to that of their C3-symmetical analogues showing that desymmetrization and functio-nalization of the discotics is feasible without undoing their self-assembly capabilities. In Chapter 4, the interaction of disc 2, possessing a peripheral 4-pyridyl group, with chiral acids is described as well as the supramolecular transfer of chirality. First several acids had to be screened to reveal which acids bind selectively with the discotic without disrupting its supramolecular properties. Apparently, acids of intermediate strength like phosphonic and tartaric acids satisfy this requirement. The appropriate chiral acids have then been used to induce chirality into the helical assemblies of disc 2 in solution. Apparently, the efficiency of the transfer of chirality is not only determined by the strength of the chiral acid, but also by steric effects. The stability of the chiral complex is highly sensitive and depends on the helix stability, the strength of the acid-base complex, and the solubility of the components. Chapter 5 deals with the incorporation of a functionalized discotic in methacrylate based polymers. Desymmetrized discotic 3 (Figure 1) carrying a dangling hydroxy group is synthesized that may act as a starting point for a wide variety of functionalized discotics. This is illustrated by transforming disc 1 into a polymerizable disc carrying a methacrylate group. This disc is then copolymerized under ATRP conditions to afford a disc-functionalized poly(butyl methacrylate) copolymer. The latter may serve as a novel material for supramolecular, fluorescent polymeric nanoparticles. In Chapter 6, a novel C3-symmetrical, heavily fluorinated disc 4 (Figure 1) is introduced. Replacing the originally hydrophobic hydrocarbon periphery by a fluorophilic fluorocarbon periphery (disc 4, Figure 1) allows helical self-assembly in fluorinated media. Teflon star 4 forms very stable columnar mesophases in which helicity may be present. Surprisingly, a proper choice of solvent combination allows the formation of mixed assemblies in which discotics possessing both a chiral, hydrocarbon periphery and fluorinated discotics 4 are present. This allows transfer of chirality from the former to the latter with the expression of amplification of chirality. Figure 1: Discotics described in this thesis. Non-symmetrical discotics 1 and 2 figure as the main topics in Chapters 2, 3 and 4. Hydroxy-disc 3 is applied in Chapter 5 and teflon disc 4 is the key molecule in Chapter 6

Non-covalent interactions in organotin(IV) derivatives of 5,7-ditertbutyl- and 5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine as recognition motifs in crystalline self- assembly and their in vitro antistaphylococcal activity

Non-covalent interactions are known to play a key role in biological compounds due to their stabilization of the tertiary and quaternary structure of proteins [1]. Ligands similar to purine rings, such as triazolo pyrimidine ones, are very versatile in their interactions with metals and can act as model systems for natural bio-inorganic compounds [2]. A considerable series (twelve novel compounds are reported) of 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp) and 5,7-diphenyl- 1,2,4-triazolo[1,5-a]pyrimidine (dptp) were synthesized and investigated by FT-IR and 119Sn M\uf6ssbauer in the solid state and by 1H and 13C NMR spectroscopy, in solution [3]. The X-ray crystal and molecular structures of Et2SnCl2(dbtp)2 and Ph2SnCl2(EtOH)2(dptp)2 were described, in this latter pyrimidine molecules are not directly bound to the metal center but strictly H-bonded, through N(3), to the -OH group of the ethanol moieties. The network of hydrogen bonding and aromatic interactions involving pyrimidine and phenyl rings in both complexes drives their self-assembly. Noncovalent interactions involving aromatic rings are key processes in both chemical and biological recognition, contributing to overall complex stability and forming recognition motifs. It is noteworthy that in Ph2SnCl2(EtOH)2(dptp)2 \u3c0\u2013\u3c0 stacking interactions between pairs of antiparallel triazolopyrimidine rings mimick basepair interactions physiologically occurring in DNA (Fig.1). M\uf6ssbauer spectra suggest for Et2SnCl2(dbtp)2 a distorted octahedral structure, with C-Sn-C bond angles lower than 180\ub0. The estimated angle for Et2SnCl2(dbtp)2 is virtually identical to that determined by X-ray diffraction. Ph2SnCl2(EtOH)2(dptp)2 is characterized by an essentially linear C-Sn-C fragment according to the X-ray all-trans structure. The compounds were screened for their in vitro antibacterial activity on a group of reference staphylococcal strains susceptible or resistant to methicillin and against two reference Gramnegative pathogens [4] . We tested the biological activity of all the specimen against a group of staphylococcal reference strains (S. aureus ATCC 25923, S. aureus ATCC 29213, methicillin resistant S. aureus 43866 and S. epidermidis RP62A) along with Gram-negative pathogens (P. aeruginosa ATCC9027 and E. coli ATCC25922). Ph2SnCl2(EtOH)2(dptp)2 showed good antibacterial activity with a MIC value of 5 \u3bcg mL-1 against S. aureus ATCC29213 and also resulted active against methicillin resistant S. epidermidis RP62A

Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007). Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of “total Al”assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2•−, generate Al superoxides [Al(O2•)](H2O5)]+ 2. Semireduced AlO2• radicals deplete mitochondrial Fe and promote generation of H2O2, O2 • − and OH•. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances