is then re-divided and wrapped around a cylinder of a different size, and this process is then repeated. the beauty of this method is that the identity of each product can be known simply by its location along the thread, and the corresponding biological activity is identified by fourier transformation of fluorescence signals. use of a traceless linker in most of the syntheses described here, it is necessary to attach and remove the starting reagent to/from a solid support. this can lead to the generation of a hydroxyl group, which can potentially affect the biological activity of a target compound. ellman uses solid phase supports in a multi-step synthesis scheme to obtain 192 individual 1,4-benzodiazepine derivatives, which are well-known therapeutic agents. to eliminate the possibility of potential hydroxyl group interference, a novel method using silyl-aryl chemistry is used to link the molecules to the solid support which cleaves from the support and leaves no trace of the linker. compounds that can be synthesized from solid-phase bound imines when anchoring a molecule to a solid support, intermediates cannot be isolated from one another without cleaving the molecule from the resin. since many of the traditional characterization techniques used to track reaction progress and confirm product structure are solution-based, different techniques must be used. gel-phase 13 c nmr spectroscopy, maldi mass spectrometry, and ir spectroscopy have been used to confirm structure and monitor the progress of solid-phase reactions. gordon et al., describe several case studies that utilize imines and peptidyl phosphonates to generate combinatorial libraries of small molecules. to generate the imine library, an amino acid tethered to a resin is reacted in the presence of an aldehyde. the authors demonstrate the use of fast 13 c gel phase nmr spectroscopy and magic angle spinning 1 h nmr spectroscopy to monitor the progress of reactions and showed that most imines could be formed in as little as 10 minutes at room temperature when trimethyl orthoformate was used as the solvent. the formed imines were then derivatized to generate 4-thiazolidinones, b-lactams, and pyrrolidines. the use of solid-phase supports greatly simplifies the synthesis of large combinatorial libraries of compounds. this is done by anchoring a starting material to a solid support and then running subsequent reactions until a sufficiently large library is built, after which the products are cleaved from the support. the use of solid-phase purification has also been demonstrated for use in solution-phase synthesis schemes in conjunction with standard liquid-liquid extraction purification techniques. deconvolution and screening combinatorial libraries combinatorial libraries are special multi-component mixtures of small-molecule chemical compounds that are synthesized in a single stepwise process. they differ from collection of individual compounds as well as from series of compounds prepared by parallel synthesis. it is an important feature that mixtures are used in their synthesis. the use of mixtures ensures the very high efficiency of the process. both reactants can be mixtures and in this case the procedure would be even more efficient. for practical reasons however, it is advisable to use the split-mix method in which one of two mixtures is replaced by single building blocks (bbs). the mixtures are so important that there are no combinatorial libraries without using mixture in the synthesis, and if a mixture is used in a process inevitably combinatorial library forms. the split-mix synthesis is usually realized using solid support but it is possible to apply it in solution, too. since he structures the components are unknown deconvolution methods need to be used in screening. one of the most important features of combinatorial libraries is that the whole mixture can be screened in a single process. this makes these libraries very useful in pharmaceutical research. partial libraries of full combinatorial libraries can also be synthesized. some of them can be used in deconvolution deconvolution of libraries cleaved from the solid support if the synthesized molecules of a combinatorial library are cleaved from the solid support a soluble mixture forms. in such solution, millions of different compounds may be found. when this synthetic method was developed, it first seemed impossible to identify the molecules, and to find molecules with useful properties. strategies for identification of the useful components had been developed, however, to solve the problem. all these strategies are based on synthesis and testing of partial libraries. the earliest iterative strategy is described in the above-mentioned document of furka notarized in 1982 and. the method was later independently published by erb et al. under the name "recursive deconvolution" recursive deconvolution. blue, yellow and red circles: amino acids, green circle: solid support recursive deconvolution the method is made understandable by the figure. a 27-member peptide library is synthesized from three amino acids. after the first (a) and second (b) cycles samples were set aside before mixing them. the products of the third cycle (c) are cleaved down before mixing then are tested for activity. suppose the group labeled by + sign is active. all members have the red amino acid at the last coupling position (cp). consequently, the active member also has the red amino acid at the last cp. then the red amino acid is coupled to the three samples set aside after the second cycle (b) to get samples d. after cleaving, the three e samples are formed. if after testing the sample marked by + is the active one it shows that the blue amino acid occupies the second cp in the active component. then to the three a samples first the blue then the red amino acid is coupled (f) then tested again after cleaving (g). if the + component proves to be active, the sequence of the active component is determined and shown in h. positional scanning positional scanning was introduced independently by furka et al. and pinilla et al. the method is based on the synthesis and testing of series of sublibraries. in which a certain sequence position is occupied by the same amino acid. the figure shows the nine sublibraries (b1-d3) of a full peptide trimer library (a) made from three amino acids. in sublibraries there is a position which is occupied by the same amino acid in all components. in the synthesis of a sublibrary the support is not divided and only one amino acid is coupled to the whole sample. as a result, one position is really occupied by the same amino acid in all components. for example, in the b2 sublibrary position 2 is occupied by the "yellow" amino acid in all the nine components. if in a screening test this sublibrary gives positive answer it means that position 2 in the active peptide is also occupied by the "yellow" amino acid. the amino acid sequence can be determined by testing all the nine (or sometime less) sublibraries. positional scanning. full trimer peptide library made from 3 amino acids and its 9 sublibraries. the first row shows the coupling positions a 27-member tripeptide full library and the three omission libraries. the color circles are amino acids omission libraries in omission libraries a certain amino acid is missing from all peptides of the mixture. the figure shows the full library and the three omission libraries. at the top the omitted amino acids are shown. if the omission library gives a negative test the omitted amino acid is present in the active component. deconvolution of tethered combinatorial libraries if the peptides are not cleaved from the solid support we deal with a mixture of beads, each bead containing a single peptide. smith and his colleagues showed earlier that peptides could be tested in tethered form, too. this approach was also used in screening peptide libraries. the tethered peptide library was tested with a dissolved target protein. the beads to which the protein was attached were picked out, removed the protein from the bead then the tethered peptide was identified by sequencing. a somewhat different approach was followed by taylor and morken. they used infrared thermography to identify catalysts in non-peptide tethered libraries. the method is based on the heat that is evolved in the beads that contain a catalyst when the tethered library immersed into a solution of a substrate. when the beads are examined through an infrared microscope the catalyst containing beads appear as bright spots and can be picked out. encoded combinatorial libraries if we deal with a non-peptide organic libraries library it is not as simple to determine the identity of the content of a bead as in the case of a peptide one. in order to circumvent this difficulty methods had been developed to attach to the beads, in parallel with the synthesis of the library, molecules that encode the structure of the compound formed in the bead. ohlmeyer and his colleagues published a binary encoding method they used mixtures of 18 tagging molecules that after cleaving them from the beads could be identified by electron capture gas chromatography. sarkar et al. described chiral oligomers of pentenoic amides (copas) that can be used to construct mass encoded oboc libraries. kerr et al. introduced an innovative encoding method an orthogonally protected removable bifunctional linker was attached to the beads. one end of the linker was used to attach the non-natural building blocks of the library while to the other end encoding amino acid triplets were linked. the building blocks were non-natural amino acids and the series of their encoding amino acid triplets could be determined by edman degradation. the important aspect of this kind of encoding was the possibility to cleave down from the beads the library members together with their attached encoding tags forming a soluble library. the same approach was used by nikolajev et al. for encoding with peptides. in 1992 by brenner and lerner introduced dna sequences to encode the beads of the solid support that proved to be the most successful encoding method. nielsen, brenner and janda also used the kerr approach for implementing the dna encoding in the latest period of time there were important advancements in dna sequencing. the next generation techniques make it possible to sequence large number of samples in parallel that is very important in screening of dna encoded libraries. there was another innovation that contributed to the success of dna encoding. in 2000 halpin and harbury omitted the solid support in the split-mix synthesis of the dna encoded combinatorial libraries and replaced it by the encoding dna oligomers. in solid phase split and pool synthesis the number of components of libraries can't exceed the number of the beads of the support. by the novel approach of the authors, this restraint was eliminated and made it possible to prepare new compounds in practically unlimited number. the danish company nuevolution for example synthesized a dna encoded library containing 40 trillion! components the dna encoded libraries are soluble that makes possible to apply the efficient affinity binding in screening. some authors apply the del for acromim of dna encoded combinatorial libraries others are using decl. the latter seems better since in this name the combinatorial nature of these libraries is clearly expressed. several types of dna encoded combinatorial libraries had been introduced and described in the first decade of the present millennium. these libraries are very successfully applied in drug research. dna templated synthesis of combinatorial libraries described in 2001 by gartner et al. dual pharmacophore dna encoded combinatorial libraries invented in 2004 by mlecco et al. sequence encoded routing published by harbury halpin and harbury in 2004. single pharmacophore dna encoded combinatorial libraries introduced in 2008 by manocci et al. dna encoded combinatorial libraries formed by using yoctoliter-scale reactor published by hansen et al. in 2009 details are found about their synthesis and application in the page dna-encoded chemical library. the dna encoded soluble combinatorial libraries have drawbacks, too. first of all the advantage coming from the use of solid support is completely lost. in addition, the polyionic character of dna encoding chains limits the utility of non-aqueous solvents in the synthesis. for this reason many laboratories choose to develop dna compatible reactions for use in the synthesis of decls. quite a few of available ones are already described materials science materials science has applied the techniques of combinatorial chemistry to the discovery of new materials. this work was pioneered by p.g. schultz et al. in the mid-nineties in the context of luminescent materials