z Organic & Supramolecular Chemistry Conformational Studies of Triazole Based Flexible Molecules: A Comparative Analysis of Crystal Structure and Optimized Structure for DNA Binding Ability Ranjeet Kumar, [a] Pratima Yadav, [a] Shiv Pal, [b] Krishnan R. Kumar, [c] Balasubramanian Sridhar, [c] and Ashish K. Tewari* [a] The present studies deal with design and synthesis of triazole based flexible molecules, their conformational analysis and DNA binding ability. The conformational studies were carried out in solid state through crystal structure and in gaseous state through theoretical calculation. The obtained conformations, found from either crystal structure or optimized most stable conformation from theoretical calculation have been screened for DNA binding ability to find importance of conformation in flexible organic molecules. Introduction Conformation is the spatial arrangement of flexible molecules through which they try to arrange themselves in the most stable and comfortable way, avoiding crowding, strain and considering the attraction or repulsion. [1] The stable conforma- tion of flexible molecules have shown prominent attention towards drugs design, DNA binding ability, macro cycle formations as well as in molecular recognitions. [2–6] The conformational analysis is important because flexible molecules can adopt different structural conformations, some of which are competent to bind to a specific binding partner receptor whereas other are not. [7–9] Previous literature revealed that U shape folded conformation of molecules is important for anti- inflammatory activity and an L-shape conformation of radicicol is bioactive and potent for HSP90 Inhibitors. [10] The stable conformation of any drug like molecules in 3D space mainly depends on non covalent C À H···N, C À H···O, C À H···p, and p···p interaction. [11] Heterocyclic systems with sulfur, nitrogen, or oxygen atom act as acceptor site and facilitate to interact with donor site either for intramolecular or intermolecular interac- tions for gaining most stable conformation. [12–15] These weak noncovalent interactions are also important to interact with biological targets via intermolecular attractive interactions such as proteins, nucleic acids, and biomembranes. [16–18] The con- formational analysis of any molecule can be determined by means of experimental techniques such x-ray crystallographic method in their solid state and through computational study in gaseous state. [19–21] We herein report the synthesis of a new series of compounds structurally containing triazole ring connected with pthalimido and pyridazinone through propylene linker (Scheme 1) for conformational studies and their DNA binding ability was assessed. The strategy for selection of these hetero- cycle derivatives have been taken place because these are already biologically active molecules and bearing strong acceptor heteroatom that facilitate efficient generation of noncovalent interaction. [22–25] The DNA binding studies were carried out by molecular docking studies perspective with crystal structure conformation and optimized lowest energy conformation. Result and Discussion Crystallography studies In this section we shall discus about the conformational analysis of compounds 2, 3, 4, 5 and 7 through crystal structure in solid state. Initially all compounds have been crystallized in different solvent among which only five compounds give x-ray quality crystal. The detailed crystallographic data, molecular structure and ORTEP diagram of all compounds have been shown in (Table 1, Figure 1 & S1-S5). The conformation for all compounds depends upon intra/intermolecular weak interac- tions like C À H···p,C À H···N and C À H···O (Table S1 and S2) as discussed here. [26–29] Compound 2 crystallized in triclinic crystal system with P-1 space group having a, b and c values as 8.6602 (9), 9.9295 (11) and 12.0058 (13) , respectively. The x-ray crystal of compound 2 has shown open structure with gauche-conformation on the propylene linker with respect to heterocyclic moieties. The [a] R. Kumar, P. Yadav, Dr. A.K. Tewari Department of Chemistry (Centre of Advanced Studies) Institute of Science Banaras Hindu University Varanasi, 221005, India E-mail: ashishtewarichem@gmail.com [b] S. Pal Indian Institute of Science Education and Research, Pune Dr. Homi Bhabha Road, Pashan, Pune 411008, India [c] Dr. K. R. Kumar, Dr. B. Sridhar Laboratory of X-ray Crystallography Indian Institute of Chemical Technology Hyderabad 500 607, India Supporting information for this article is available on the WWW under https://doi.org/10.1002/slct.201700240 Full Papers DOI: 10.1002/slct.201700240 3444 ChemistrySelect 2017, 2, 3444 – 3451  2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim