Cooperativity of Non-Covalent Interactions

G. Narahari Sastry Centre for Molecular Modeling

Indian Institute of Chemical Technology Hyderabad – 500 607, INDIA

gnsastry@gmail.com http://203.199.182.73/gnsmmg/

79th Annual Meeting of Indian Academy of Sciences Chandigarh, 8 – 10 November 2013

Current Ph.D./Project Students •  Neela •  Bhaskar Sharma •  Richard Prem Kumar •  U. Purushotham •  Altaf Hussain •  Uma Devi •  Chinmayee •  Ram Vivek •  Srikanth •  Sirisha Scientists in the Group •  Dr. Y. Soujanya •  Dr. G. Gayatri •  Dr. Swati Pannigrahi •  Dr. S.Janardhan •  Dr. Anirban

Past Ph.D. Students Dr. U. D. Priyakumar Dr. T.C. Dinadayalane Dr. J. Narashimamoorthy Dr. A. Srinivas Reddy * Dr. P. Srivani Dr. M. Nagaraju Dr. G. Gayatri Dr. Dolly Vijay * Dr. J. Srinivasa Rao Dr. B. Sateesh Dr. R.G. Kulkarni Dr. M. Chourasia Preethi Badrinarayan A. Subha Mahadevi *

Collaborators Dr. G.Madhavi Sastry Dr. Devesh Kumar Prof. H. Sakurai Prof. S.P. de Visser Prof. H. Zipse Prof. A. R. Rao Prof. G. Achaiah Prof. S.R. Gadre Prof. E.D. Jemmis Prof. S.R. Gadre Dr. M. Vairamani Dr. A. Kamal Prof. S. Bapiraju Prof . S. Durga Bhavani

Funding: CSIR, DST, DBT, DAE(BRNS), Indo-German(DST-DAAD), Indo-Japan (INSA-JSPS)

Acknowledgements

Molecules Clusters Crystal structure

Are the properties of the clusters similar to bulk properties of larger aggregates like crystals?

Water: From Clusters to the Bulk 'Water is H2O, hydrogen two parts, oxygen one, but there is also a third thing, that makes it water and nobody knows what it is’ !!

D H Lawrence (1885-1930)  

  Water clusters are small groupings of water molecules that differ in many ways from bulk water

  Unlike bulk water, most of the molecules in a small cluster are on the surface, where they have fewer chemical interactions with other water molecules

Formation of clusters from individual units

Animations from Martin chaplin,s website

Physical properties of such clusters vary according to their relative concentrations

Hydrogen bonded networks and cooperativity

In 1957, Wen et al. were the first to discuss the importance of many-body effects in

water in their description of the cooperativity of hydrogen bonds

Structural aspects of ion-solvent interaction in aqueous solutions: A suggested picture of water structure, Frank, H. S.; Wen, W. Y. Discuss. Faraday. Soc. 1957, 24, 133

They postulated that the formation of hydrogen bonds in water is predominantly a

cooperative phenomenon

“When one bond forms several will form, and when one bond

breaks then, typically a whole cluster will dissolve.”

Proposed resonance scheme for hydrogen bond in water

+

+ + E (kcal/mol)

Formamide units

Formamide chain

Cooperativity in Amide Hydrogen Bonding Chains. Relation between Energy, Position, and H-Bond Chain Length in Peptide and Protein Folding ModelsKobko, N.; Dannenberg J. J. J. Phys. Chem. A 2003, 107, 10389-10395 Cooperativity in Amide Hydrogen Bonding Chains. A Comparison between Vibrational Coupling through Hydrogen Bonds and Covalent Bonds. Implications for Peptide Vibrational SpectraKobko, N.; Dannenberg J. J. J. Phys. Chem. A 2003, 107, 6688-6697

• B3LYP/D95** calculations for linear H-bonded formamide (n = 2 – 15) • Their studies reveal cooperative effect of 200% over dimer particularly those bonds in centre of chain

Studies on Cooperativity in linear formamide chains

Interaction enthalpies for H-bonds organized by H-bond type (k) for chains of the lengths indicated by the symbols

Variation of frequencies and intensities for the H-bonding N-H stretches in formamide chains.

Manifestation of hydrogen bond cooperativity as a function of increasing cluster size

and varying arrangement of molecules is explored using formamide [HCONH2]n (n =

1-10) clusters based on DFT calculations.

Mahadevi, A. S.; Neela, Y. I.; Sastry G. N. J. Chem. Sci. 2012, 124, 35-42

Cooperativity in Formamide Clusters (Structural, Energetic, Spectroscopic)

Cooperativity of Hydrogen Bonding in Acetamide Clusters

How much of cooperativity is a function of size of cluster? , and how much is it

due to individual arrangement? Mahadevi ,A. S.; Neela, Y. I.; Sastry, G. N. Phys. Chem. Chem. Phys. 2011, 13,15211-15220

Cooperativity in Acetamide Clusters

Graphical plot of relative energy (RE in kcal mol-1) versus number of monomers for circular and standard arrangements with respect to (w.r.t) the linear arrangement of acetamide, n=2–15, at the B3LYP/D95** level of theory

As the cluster size increases the relative energy of both circular and standard forms

increases on comparison to the corresponding linear form

Naturally occurring forms of Water Clusters

Ice XI, and its repeating unit Buch, V.; Sandler, P.; Sadlej, J. J. Phys. Chem. B 1998, 102, 8641.

Helical water chain Saha, B. K.; Nangia, A. Chem. Commun. 2005, 3024. Barbour, L. J.; Orr, G. W.; Atwood, J. L.

Nature. 1998, 393, 671.

Supra molecular complex in aqueous medium along with repeating unit of

water here

Ice Ih and its repeating unit Distribution of water at micellar surface mimicking

protein surface

Biological water Materer, N.; Starke, U.; Barbieri, A.; Van Hove, M. A.; Somorjai, G. A.; Kroes, G. J.; Minot, C. J. Phys. Chem. 1995, 99, 6267.

Nandi, N.; Bagchi, B. J. Phys. Chem. B 1997, 101, 10954

Pal, S. K.; Peon, J.; Zewail, A. H. Proc. Natl. Acad. Sci. 2002,

99, 15297 Neela, Y. I.; Mahadevi, A. S.; Sastry G. N. J. Phys. Chem. B 2010, 114, 17162

Encapsulated water wire in peptide

Raghavender U. S.; Aravinda K. S.; Shamala N.; Balaram P J. Am. Chem. Soc. 2010, 132, 1075

Water chains Natarajan, R.; Charmant, J. P. H.; Orpen, A. G.; Davis A. P. Angew. Chem. Int. Ed. 2010, 49, 5125.

Buehler, M. J. Nature Nanotech. 2010, 5, 172-173.

Knowles, T. P. J.; Oppenheim, T. W.; Buell, A. K.; Chirgadze,

D. Y.; Welland M. E. Nature Nanotech. 2010, 5, 204-207

Hydrogen Bond 3Å

βStrand 2nm

Amyloid fibril 8-10nm

Amyloid fibre 100s of nm Amyloid

plaque >100nm

Self assembly of proteins in amyloids: an inspiration to create multifunctional macroscopic materials

G.; Rossetti, A.; Magistrato, A.; Pastore, P. Carloni, J. Chem. Theory Comput. 2010, 6, 1777.

The cooperativity of glutamine

side chains affects both the

directions perpendicular and

parallel to the backbone.

Polyglutamine β-sheet aggregates

a r e a s s o c i a t e d w i t h t h e

derangement of Hunt ington’s

disease.

The effect of cooperativity control

the structure and energetics of the

aggregates.

Studies on Cooperativity in Hydrogen Bonding in polyQ -Sheets

Synergy in Noncovalent Interactions-Important Questions ?

Do they behave differently in the

presence of each other ? Mutual impact

Do their properties vary when several of the same

kind of non-bonded interactions occur

together ? Size Effect

How does this impact supramolecular

assembly ? Aggregation

π π Cation π

Hydrogen Bond

Van der Waals?

Spiny-tail gecko lizard has a total Clining force of over 20N, though the Little Lizard weighs only about 40g!

Glue?

Suction?

Friction?

Capillary Forces?

Claws?

π; π π; π,

π,

Central Dogma in Biology: π-π

Interactions in Molecules

Enonbonded = Eelectrostatic + Einduction + ECT + Edispersion + Eexchange-repulsion

  Electrostatic multipole – multipole   Induction multipole-induced multipole   Dispersion instantaneous multipole-induced multipole   CT - charge transfer from donor to acceptor   Exchange electron exchange

van der Waals electrostatic

E = Ebend + Estretch + Etorsion + Evan der Waals + Eelectrostatic

Bonded Non-Bonded

Distance dependencies of Non-Covalent Interactions

Chem. Rev., 2013, 113, 2100-2138.

Cation-π interactions 1.  Arguably the strongest among different non-bonded interactions

2.  Tunability of cation-π interactions is effected by subtle variation of key factors

•  Size of π system

•  Solvent Effect

•  Nature of cation

•  Cation-π vs. Cation-σ

•  Substituent

•  Counter-Ion

3. Cooperativity of cation-π interactions with other non-bonded interactions

4.  Significant impact in several fields including chemistry, biology, material science,

nanosystems, host guest interaction, catalysis and reaction mechanisms…

5. Potential application in developing scoring functions and drug design

Exploring the Coexistence of M-π and π-π Interactions in Biology and Chemistry

Reddy. A. S.; Vijay, D.; Sastry, G. M.; Sastry, G. N. J. Phys. Chem. B, 2006, 110, 2479 Reddy. A. S.; Vijay, D.; Sastry, G. M.; Sastry, G. N. J. Phys. Chem. B, 2006, 110, 10206

Two key non-covalent forces namely cation-π and π-π, which govern the macromolecular structure, work in concert

Table: π-π interactions Interaction Energies (in kcal/mol) of the Various Benzene Dimers in the Presence of Metal Ion

Cooperativity – Its Universality

Cooperativity

Important Questions ??? Unambiguous

quantitative measure in large system with

multiple kinds of weak interactions

Biological Context

Supramolecular Assembly Catalysis

Potential Applications (design of novel material)

Synonymous Terminology Non-Additivity Synergy Cooperativity

Our contribution to the concept of cooperativity A clear and unambiguous measure for cooperativity in ternary systems

J. Phys. Chem. B, 2006, 110, 2479 J. Phys. Chem. B, 2006, 110, 10206

J. Phys. Chem. B, 2008, 112, 8863 Chem. Phys. Lett, 2010, 485,235 Cation-π and hydrogen bonding Cation-π and π-π

J. Phys. Chem. B, 2010 , 114, 17162; J. Chem. Phys. 2010, 133, 164308; Phys. Chem. Chem. Phys. 2011, 13,15211 ; J. Chem. Sci. 2012, 124, 35

Coexistence of Cation and π- π interactions

NAME METHODOLOGY Morokuma

Analysis Eint = ES + PL + EX + CT + MIX (Kitaura, K.; Morokuma, K. Int. J. Quantum Chem. 1976, 10, 325: Zhu, W.; Luo, X.; Puah, C. M.; Tan, X.; Shen, J.; Gu, J.; Chen, K.; Jiang, H. J. Phys. Chem. A 2004, 108, 4008 )

ES = Electrostatic, PL = Polarization, EX = Exchange, CT = Charge Transfer, MIX = cross

(SAPT) Symmetry Adopted

Perturbation Theory

Eint = E(1)es+E (1)

exch+E (2) ind+E (2) exch –ind +E (2) disp+ E (2) exch - disp+δHFint

= Ees+ Eexch +Eind+Edisp (Jeziorski, B.; Moszynski, R.; Szalewicz, K. Chem. Rev 1994,94, 1887: Kim,

D.; Tarakeshwar, P.; Kim, K. S. J. Phys.Chem. A 2004,108, 1250)

E(1)es = Electrostatic, E (1)

exch= 1st order valance repulsion due to pauli exclusion, E (2) ind= 2nd order energy gain resulting from induction interaction, E (2) exch –ind = Repulsion change due to electron cloud deformation, E (2) disp = 2nd order dispersion energy, E (2) exch – disp= 2nd order dispersion correction for a coupling between the exchange repulsion and the dispersion interaction.

δHFint = Higher order induction and exchange correction.

(MIPP) Molecular Interaction Potential

Eint= Ee+Evw+Ep ( Lugue, F. J.; Orozco, M.; J. Comput. Chem. 1998, 19, 866: Garau, C.; Frontera, A.; Quinonero, D.; Ballester, P.; Costa, A.; Deya, P. M. Chem. Phys. Lett. 2004, 392, 85) Ee= Electrostatic Evw= Sum of dispersion and repulsion energies Ep= Polarization

Energy Partition Schemes

(BLW-ED) Block-localized wave function

approach

EHF = Edist+ Ees+ Eex+ Epol+ Ect ( Mo, Y.; Gao, J. Chem. Phys 2000, 112, 5530: Mo, Y.; Song, L.; Wu, W.; Zhang, Q. J. Am. Chem. Soc. 2004, 126, 3974)

EMP2 = Edist+ Ees+ Eex+ Epol+ Εct + Ecorr Edist = Geometry distortion, Ees= Electrostatic, Eex= Exchange repulsion, Epol = Polarization, Εct = Charge transfer Ecorr = Electron Correlation

Reduced Variational Space (RVS) Analysis

Energy Decomposition Analysis

Manifestation of cooperativity and the various aspects of the concept

Understanding the role, range and relevance of non-covalent interactions, particularly, h-bonding, cation-π and π-π interactions are of outstanding importance in biology, chemistry, material science and all molecular sciences.

Cooperativity is a fascinating phenomenon, and understanding how it operates and manifests in supramolecular assemblies is interesting in its own right. (Energetic, Structural, Spectral and Functional issues)

Concluding Remarks

"It is certain that all bodies whatsoever, though they have no sense,

yet they have perception; for when one body is applied to another,

there is a kind of election to embrace that which is agreeable, and

to exclude or expel that which is ingrate; and whether the body be

alterant or altered, evermore a perception precedeth operation; for

else all bodies would be like one to another." Francis Bacon

(abou.1620)