Crystal Engineering and Supramolecular Chemistry

Supramolecular chemistry is the branch of chemistry that deals with the assembly of molecules and their associations in the crystalline solid. Crystal engineering is a direction of supramolecular chemistry aimed at designing the 3D periodic structure with the desired supramolecular structure. A lot of work has been carried out to understand the nature of intermolecular forces that dictate the molecular organization in the solid-state. Knowledge of such interactions greatly helps to design the molecular assembly of choice such as pharmaceutical cocrystals, explosive cocrystals, material for chiral resolution, fluorescent cocrystals, etc. Our research group is involved in the study of intermolecular interactions, understanding their nature, and utilizing this knowledge for the construction of functional solids. We have been working on the crystal engineering for p-stacking interactions to achieve the required molecular geometry in the crystals lattice by modulating the substituents (electron-donating and election-withdrawing) of organic scaffolds. 

Representative Publications: 

  1. R. L. Gawade, D. K. Chakravarty, A. Kotmale, E. Sangtani, P. V. Joshi, A. Ahmed, M. V. Mane, S. Das, K. Vanka, P. R. Rajamohanan, V. G. Puranik,* R. G. Gonnade*, Cryst. Growth Des. 201616, 2416-2428. DOI: 10.1021/acs.cgd.6b00204.
  2. V. Koshti, S. Thorat, R. Gote, S. H. Chikkali*, R. Gonnade*, CrystEngComm., 2016, 18, 7078 - 7094 (2016), DOI: 10.1039/C6CE01324D.
  3. S. R. Shaikh, R. L. Gawade, D. Kumar, A. Kotmale, R. G. Gonnade,* T. Stürzer, Cryst. Growth Des201919, 5665-5678. DOI: 10.1021/acs.cgd.9b00667.



Polymorphism and Structural Phase Transition in Molecular Crystals

Polymorphism, the ability of a compound to exist in more than one crystalline form due to different conformation and/or arrangement of identical molecules in the crystal lattice, has been studied extensively for the last three decades because of its implications in chemical and pharmaceutical industries. Polymorphism in molecular crystals is one of the manifestations of noncovalent intermolecular interactions which play a vital role in the assembly of molecules in a crystal. Molecules which are devoid of strong intermolecular interaction in their association in the crystals  are organized in the crystal lattice via energetically weaker interactions or van der Waals’ forces, and these solids often exhibit polymorphic behaviour. The relative stability of polymorphs varies, and hence they often exhibit structural phase transitions. This is an important aspect of research relevant to crystal engineering, crystal structure prediction, and structure and property correlation in functional solids. When these transitions are between two or more crystalline phases, analysis of intermolecular interactions can provide clues about the possible molecular movements during phase transformation.

 Representative Publications: 

  1.  M. I. Tamboli,  S. Krishnaswamy, R. G. Gonnade*, and M. S. Shashidhar*, Cryst. Growth Des. 2014, 14, 4985−4996. DOI:10.1021/cg5005227.
  2. M. I. Tamboli, V. Bahadur, R. G. Gonnade*, M. S. Shashidhar*, Cryst. Growth Des., 2015, 15, 1226 - 1232. DOI:10.1021/cg501620g. 
  3. M. I. Tamboli, D. P. Karothu, M. S. Shashidhar, R. G. Gonnade,*cand P. Naumov*, Chem. Eur. J. 2018, 24, 4133 – 4139. DOI:10.1002/chem.201705586.
  4. B. P. Mali, S. R. Dash, S. B. Nikam, A. Puthuvakkal, K. Vanka, K. Manoj* and R.G. Gonnade*, Acta Cryst. 2020, B76, 850-864.



Five Concomittant Polymorphs of Green Fluorescent Protein Chromophoe (GFPc) Analogue:

Understanding Variations is Photoluninescence  with pi-Stacking Interactions.

Acta Cryst. 2020, B76, 850-864;


Drug Polymorphism and Pharmaceutical Multicomponent Crystals

The recent guidelines by US FDA recommend polymorph screening of every drug substance including solvates and hydrates as polymorphs of a drug substance displays different physicochemical properties that include melting point, chemical reactivity, apparent solubility, dissolution rate, optical and mechanical properties, vapor pressure, and density. These properties can have a direct effect on the ability to process and/or manufacture the drug substance and the drug product, as well as on drug product stability, dissolution, and bioavailability. Thus, polymorphism can affect the quality, safety, and efficacy of the drug product. Hence, FDA needs information on each crystal form of the drug substance and that change during manufacturing, storage to be understood and documented. Additionally, polymorphs and other solid forms are treated as patentable inventions by FDA and are considered seriously by pharmaceutical industries to develop their IP portfolio. Therefore, the modern drug development program is not only focused on the discovery of new chemical entities (NCE), but also on exploring ways in which the existing drug substances can be used effectively by finding new solid forms of the active substance having desired physicochemical and biopharmaceutical properties. Amongst various approaches polymorph and cocrystal screening has emerged as an alternative and viable strategy to address development and formulation issues of APIs in the pharmaceutical industry. The results of the polymorph screening give a clear understanding of the polymorphism of the product which allows the industry to bring it to market quickly and efficiently. Our group is involved in the development of novel crystalline/amorphous polymorphs, cocrystals, salts, eutectic including hydrates and solvates of the industrially important identified APIs which belongs to BCS class II and IV drug category (low solubility and low permeability category) with an objective to enhance their solubility and permeability which will have its direct effect on the bioavailability and therapeutic efficacy.

Representative Publications:

  1. Shridhar H. Thorat, Christy P. George, Parth S. Shaligram, Suresha P. R. and Rajesh G. Gonnade*, CrystEngComm.202122. DOI:  10.1039/D1CE00032B 

  2. E. Sangtani, S. K. Mandal, A. S. Sreelakshmi, P. Munshi, R. G. Gonnade*, Cryst. Growth & Des., 2017, 17, 3071 - 3087. DOI: 10.1021/acs.cgd.6b01868.
  3. E. Sangtani, S. K. Sahu, S. H. Thorat, R. L. Gawade, K. K. Jha, P. Munshi, R. G. Gonnade*, Cryst. Growth & Des., 2015, 15, 5858 - 5872. DOI: 10.1021/acs.cgd.5b01240.
  4. C. P. George, S. H. Thorat, P. S. Shaligram, P. R. Suresha, R. G. Gonnade*, CrystEngComm., 2020, 22. DOI: 10.1039/D0CE00353K.
  5. R. G. Gonnade*, E. Sangtani, J. Ind. Inst. Sci., 201797, 193 - 226. DOI:10.1007/s41745-017-0028-2.
  6. S. H. Thorat, S. K. Sahu, M. V. Patwadkar, M. V. Badiger, R. G. Gonnade*, J. Pharm. Sci., 2015, 104, 4207 - 4216. DOI: 10.1002/jps.24651.
  7. S. H. Thorat, M. V. Patwadkar, R. G. Gonnade*, R. Vaidhyanathan, CrystEngComm., 2014, 16, 8638 - 8641. DOI: 10.1039/C4CE01446D.



Enantiomeric Resolution by Recrystallization

Enantiomeric separation of chiral compounds is one of the most intensively researched topics in recent times because of its potential application in pharmaceuticals, dyes, agrochemicals and speciality chemical industries. Generally, a chemical synthesis of chiral systems results in racemates, i.e. 50:50 mixtures of right and left handed molecular forms, called enantiomers. More than 50% of the commercially available drugs are chiral to exist as a mixture of enantiomers. Although physico-chemical properties of the enantiomers differ only in their optical rotation, their pharmacological activity differs substantially. Different pharmacokinetic properties between enantiomers may contribute serious side effects. Therefore, inactive enantiomer should be separated before drug formulation. Although chiral separation is a difficult process due to the identical chemical and structural properties of the enatiomers and this implies extreme increases in production costs. Therefore reliable/cheap and environmentally favorable chiral separation methods need to be investigated. Among the various method of enantiomeric separation, resolution by crystallization (preferential enrichment of enantiomers and by preferential crystallization of conglomerates) is gaining much interest because of its feasibility, less labor, hazardless, and economically and environmentally acceptable method. Interestingly, the separation of enantiomers by such a simple crystallization process does not require the use of any external enantiopure entity and, hence, require relatively less effort to scale up (as compared to chemical methods of separation of enantiomers).


Representative Publications:

  1. N. T. Patil, M. T. Patil, N. Sarkar, R. G. Gonnade*, M. S. Shashidhar*,  Cryst. Growth & Des.2021
  2. N. T. Patil, M. S. Shashidhar*, M. I. Tamboli, R. G. Gonnade*,  Cryst. Growth & Des., 2017, 17, 5432-5440. DOI:10.1021/acs.cgd.7b00895.
  3. R. G. Gonnade, S. Iwama, R. Sugiwake, K. Manoj, H. Takahashi, H. Tsue, R. Tamura*, Chem. Commun., 2012, 48, 2791–2793. DOI:10.1039/C2CC18132K.
  4. R. Tamura, S. Iwama, R. G. Gonnade, CrystEngComm, 2011, 13, 5269-5280. DOI:10.1039/c1ce05294b (review article).
  5. S. Iwama, K. Kuyama, Y. Mori, K. Manoj, R. G. Gonnade, K. Suzuki, C. E. Hughes, P. A., Williams, K. D. M. Harris, S. Veesler, H. Takahashi, H. Tsue, R. Tamura, Chem. Eur. J., 2013, 3529 – 3542. DOI:10.1002/ejoc.201201739.



Group Transfer Reactions in Molecular Crystals

Representative Publications:

  1. M. I. Tamboli, M. S. Shashidhar*, R. G. Gonnade*, S. Krishnaswamy, Chem. Eur. J., 2015, 21, 13676 – 13682. DOI:10.1002/chem.201501480.
  2. M. I. Tamboli, S. Krishnaswamy, M. S. Shashidhar*, R. G. Gonnade*, Chem. Eur. J.2013, 19, 12867 – 12874. DOI:10.1002/chem.201301058.
  3. M. I. Tamboli, S. Krishanaswamy, R. G. Gonnade*, M. S. Shashidhar,  Acta Cryst., 2016, C72, 875 – 881. DOI:10.1107/S205322961601603X.