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April 2013

Vol. XCI, No. 8

The Esselen Award Meeting at Harvard Award to Frantiek Tureek and Michael H. Gelb

Monthly Meeting Summer Scholar Report

February Meeting Report

By Jack Driscoll with photos by James Phillips

By Morris E. Cohen, Adam Moser and Binyomin Abrams, Boston University Department of Chemistry

2012 Golf Tournament Report

By Amy Tapper with photos by Amy Tapper

Call for Nominations

The 2013 James Flack Norris Award for Outstanding Achievement in the Teaching of Chemistry Deadline: April 15, 2013 Nominations are invited for the 2013 James Flack Norris Award, which consists of a certificate and an honorarium of $3,000 and is given annually by the Northeastern Section (NESACS). The presentation will take place at a ceremony and dinner in November 2013, and will include a formal address by the awardee. The Award was established in 1950 by NESACS to honor the memory of James Flack Norris (1871-1940), a professor of chemistry at Simmons College and M.I.T., chair of NESACS in 1904, and ACS President in 1925-26.

Nominees should have served with special distinction as teachers of chemistry at any level: secondary school, college, and/or graduate school. With the presentation of the first Award in 1951, awardees have included many eminent teachers at all levels whose efforts have had a wide-ranging effect on chemical education. The recipient will be selected from an international list of nominees who have served with special distinction as teachers of chemistry with significant achievements. A nomination in the form of a letter should focus on the candidates contributions to and effectiveness in teaching chemistry. The nominees curriculum vitae should be included and, where appropriate, a list of honors, awards, and publications related to chemical education. Seconding letters may also be included; these should show the impact of the nominees teaching for inspiring colleagues and students toward an active life in the

chemical sciences, and attest to the influence of the nominees other activities in chemical education, such as textbooks, journal articles, or other professional activity at the local, national, and international level. The nomination materials should consist of the primary nomination letter, supporting letters, and the candidates curriculum vitae. Reprints or other publications should NOT be included. The material should not exceed thirty (30) pages, and should be submitted electronically in Adobe PDF format through April 15, 2013 to Ms. Anna Singer, NESACS Administrative Secretary <secretary@nesacs.org>. For more information about the Award, see http://www.nesacs.org/awards_norris.html>. Questions about the Award or the nomination process should be directed to the Chair of the Norris Award Committee, Professor Mary Shultz, <Mary.Shultz@Tufts.edu>. u

The Nucleus April 2013

The Northeastern Section of the American Chemical Society, Inc. Office: Anna Singer, 12 Corcoran Road, Burlington, MA 01803 (Voice or FAX) 781-272-1966. e-mail: secretary(at)nesacs.org NESACS Homepage: http://www.NESACS.org Officers 2013 Chair Liming Shao 158South Great Road Lincoln, MA 01773 limingshao(at)comcast.net shao(at)fas.harvard.edu 781-518-0720 Chair-Elect Catherine Costello Boston University School of Medicine 670 Albany Street, room 511 Boston, MA 02118-2646 Cecmsms(at)bu.edu Immediate Past Chair Ruth Tanner Olney Hall 415B Lowell, MA 01854 University of Mass Lowell Ruth_Tanner(at)uml.edu 978-934-3662 Secretary: Michael Singer Sigma-Aldrich 3 Strathmore Rd, Natick, MA 01360 774-290-1391, michael.singer(at)sial.com Treasurer: James Piper 19 Mill Rd, Harvard, MA 01451 978-456-3155, piper28(at)attglobal.net Auditor: Anthony Rosner Archivist Tim Frigo Trustees: Peter C. Meltzer, Esther A. H. Hopkins, Michael E. Strem Directors-at-Large David Harris, Stephen Lantos, James Phillips, Ralph Scannell, Mary Burgess, John Burke Councilors Alternate Councilors Term Ends 12/31/2013 Alfred Viola Mark Froimowitz Michael Singer Sophia R. Su Robert Lichter Kenneth C. Mattes Mary Shultz Tim Frigo Leland L. Johnson, Jr. Mukund Chorghade Term Ends 12/31/2014 Katherine Lee C. Jaworek-Lopes Michael P. Filosa Lawrence Scott Doris Lewis Andrew Scholte Morton Z. Hoffman Raj Rajur Patrick Gordon John Podobinski Mary Burgess Stuart Levy Term Ends 12/31/2015 Catherine E. Costello Marietta Schwartz Ruth Tanner JerryJasinski Dorothy J. Phillips Stephen Lantos Michaeline Chen Norton P. Peet Jackie ONeil Wilton Virgo

Contents
Call for Nominations ____________________________________2
2013 James Flack Norris Award for Outstanding Acheivement in the Teaching of Chemistry By Jack Driscoll, NESACS Public Relations Chair. Photos by James Phillips. (Cover photo by Morton Z. Hoffman).

February Monthly Meeting Report _________________________4 Monthly Meeting _______________________________________5

Esselen Award Meeting at the Harvard Faculty Club and Pfizer Lecture Hall, Award to Frantiek Tureek and Michael H. Gelb By Amy Tapper with photos by Amy Tapper

8th Annual NESACS Golf Tournament Report _________________6 9th Annual NESACS Golf Tournament Announcement ___________7 Summer Scholar Report _________________________________8
Towards an All-Atom Model for m-Poly(phenylene ethynylene) Class of Foldamers using theCHARMM27 Force Field: Structure and Unfolding Pathway of Foldamers of Various Lengths Morris E. Cohen, Adam Moser, and Binyomin Abrams, Department of Chemistry, Boston University, Boston MA

Cambridge Science Festival Annoucement __________________12 NESACS at Fenway Park-May 10, 2013 ____________________16 Cover: A photo from the February Meeting at Northeastern University, 140 The
Fenway. Pictured (L-R) are Liming Shao, 2013 NESACS Chair; Februarys speaker, Jeannette Brown, Merck retired; and Prof. Patricia Mabrouk, Northeastern University, NESACS WCC Chair. Photo by Morton Z. Hoffman. September 2013 Issue: July 15, 2013

Editorial Deadlines: Summer 2013 Issue: June 15, 2013

All Chairs of standing Committees, the editor of THE NUCLEUS, and the Trustees of Section Funds are members of the Board of Directors. Any Councilor of the American Chemical Society residing within the section area is an ex officio member of the Board of Directors.

The Nucleus is published monthly, except June and August, by the Northeastern Section of the American Chemical Society, Inc. Forms close for advertising on the 1st of the month of the preceding issue. Text must be received by the editor six weeks before the date of issue. Editor: Michael P. Filosa, Ph.D., ZINK Imaging, Inc., 16 Crosby Drive, Building 4G, Bedford, MA 01730 Email: Michael.filosa(at)zink.com; Tel: 508-843-9070 Associate Editors: Myron S. Simon, 20 Somerset Rd., W. Newton, MA 02465, Tel: 617-332-5273, Sheila E Rodman, Email: serodman(at)hotmail.com, Mindy Levine, 516-697-9688, mindy.levine(at)gmail.com Board of Publications: Mary Mahaney (Chair), Mindy Levine, Vivian K. Walworth, James Phillips Business Manager: Karen Piper, 19 Mill Rd., Harvard, MA 01451, Tel: 978-456-8622 Advertising Manager: Vincent J. Gale, P.O. Box 1150, Marshfield, MA 02050, Email: Manager-vincegale(at)mboservices.net; Tel: 781-837-0424 Contributing Editors: Morton Hoffman, Feature Editor; Dennis Sardella, Book Reviews Calendar Coordinator: Sheila Rodman, email: serodman(at)hotmail.com Photographers: Morton Z. Hoffman and James Phillips Proofreaders: Donald O. Rickter, Vivian K. Walworth, Mindy Levine Webmaster: Roy Hagen Copyright 2013, Northeastern Section of the American Chemical Society, Inc.
The Nucleus April 2013 3

February Monthly Meeting

By Jack Driscoll, Public Relations Chair, NESACS

Corporate Patrons $2000 - or more

AstraZeneca Pharmaceuticals Eisai Pharmaceuticals EMD Serono Genzyme Corp. Johnson Matthey Merck & Co. Novartis Pfizer Inc. Schering Corp. Strem Chemicals, Inc. Vertex Pharmaceuticals

Dorothy Phillips (l) and Jeanette Brown with her new book- (Photo by James Phillips)

The February monthly meeting of NESACS was held at Northeastern University at 140 The Fenway across from the Museum of Fine Arts. The building was formerly the site of the Forsythe Institute. Parking was difficult as a result of the recent blizzard in Bostons very snowy February. Our guest speaker was Jeanette Brown, formerly an organic chemist for CibaGeigy and Merck, where she (http://www.thehistorymakers.com/bio graphy/jeannette-brown-42) developed drugs for diseases such as tuberculosis

Ruth Tanner, NESACS Immediate Past Chair (l), Jeanette Brown, Liming Shao, NESACS 2013 Chair (Photo by James Phillips)

$1000-$1999
Boehringer Ingelheim GlaxoSmithKline Irix Pharmaceuticals Lyophilization Services of NE Sundia Meditech Yes Bank

and coccidiosis. The location of the meeting was arranged by Prof. Pam Mabrouk of Northeastern University. After her industrial career, Jeanette was appointed chairperson of the Project SEED Committee for the American Chemical Society. She also served on the faculty of the New Jersey Institute of Technology (NJIT) as a visiting professor of chemistry and a faculty associate. She was interested in science education and biographies of African American chemists. She went

$300-$999
Cambridge Major Labs Girindus Merrimack Consultants Organix PCI Synthesis Sigma Aldrich Waters Corp. Wilmington PharmaTech

Jack Driscoll, PR Chair NESACS, Patricia Mabrouk, Woman Chemists Committee Chair, NESACS (Photo by James Phillips)

on to publish her own book in 2011, entitled, African American Women Chemists, which was her topic for our February meeting of NESACS. This book was published by Oxford University Press and is readily available at retailers such as Amazon. The monthly meetings typically involve a board meeting from 4:305:30pm followed by an hour of networking with hor doeuvres and beverages, followed by dinner and capped with a talk by an interesting
continued on page 13
4 The Nucleus April 2013

Monthly Meeting
The 932nd Meeting of the Northeastern Section of the American Chemical Society
Thursday, April 4, 2013 Harvard University, Cambridge, MA Harvard Faculty Club, 20 Quincy Street 4:30 pm Board Meeting 5:30 pm Social Hour 6:30 pm Dinner 8:15 pm Award Meeting, Mallinckrodt Building, 12 Oxford St. Pfizer Lecture Hall (MB23), ground floor. Dr. Liming Shao, NESACS Chair, presiding Welcome Dr. Anna Sromek, Chair, Esselen Award Committee The Esselen Award - Dr. Myron S. Simon, Founding Member of the Esselen Award Committee Introduction of the Award Recipients Dr. Paul B. Hopkins, Chair, Department of Chemistry, University of Washington. Presentation of the Award - Gustavus J. Esselen, IV Michael H. Gelb, Harry and Catherine Jaynne Boand Professor of Chemistry, and Frantiek Tureek, Professor of Chemistry, University of Washington. Lecture: The Chemistry of Next Generation Newborn Screening Dinner reservations should be made no later than noon, Thursday, March 28. Reservations are to be made using PayPal services: http:// acssymposium.com/paypal.html. Select pay with credit or debit card option and follow the additional instructions on the page. Members, $30; Non-members, $35; Retirees, $20; Students, $10. Reservations for new members and for additional information, contact the secretary Anna Singer at (781)272-1966 between 9am and 6pm or e-mail at secretary@nesacs.org. Reservations not cancelled at least 24 hours in advance must be paid. THE PUBLIC IS INVITED Free Parking in the Broadway Street garage (3rd level or higher), enter from Cambridge St. via Felton St.

Biographies
Dr. Frantiek Tureek

Abstract
The Chemistry of Next Generation Newborn Screening Newborn screening of inborn errors of metabolism is an important modern component of public health that allows detection of several genetic disorders enabling the start of early treatment of affected children. We have developed new chemical methods for rapid and reliable measurements of enzyme activities that are indicative of genetic

defects associated with lysosomal storage disorders, porphyrias, and congenital disorders of glycosylation. The first part of the lecture will deal with the technique of affinity capture-release mass spectrometry and its applications to clinical enzymology and proteomics. The second part will address the detection by tandem mass spectrometry of lysosomal storage disorders in dried blood spots and recent progress in multiplexing our analytical methods for large-scale newborn screening. u

Dr. Frantiek Tureek was born in Prague, Czechoslovakia, where he received a Ph.D. in organic chemistry from Charles University in 1977. In 1987 he and his family left Czechoslovakia, and, after spending a year in a refugee camp, they moved to the United States, where he joined Fred McLafferty at Cornell University. In 1990 he joined the faculty of the Chemistry Department at University of Washington, Seattle. His research interests have been in the chemistry of highly reactive molecules (enols, sulfenic acids), hypervalent radicals, nucleobase radicals related to DNA damage, and peptide radicals and cation-radicals. His other interests include mass spectrometric instrumentation, gas-phase ion chemistry, ionsurface interactions (soft and reactive landing), and applications to proteomics, clinical analysis, and newborn screening. He is author of >370 scientific papers, three books, and several patents. Among his recent awards are the P. B. Hopkins Faculty Award, the Czech Head-Patria Science Prize, the Johannes Marcus Marci Spectroscopy Award, and the Thomson Medal of the International Mass Spectrometry Federation. Michael H. Gelb Professor Michael H. Gelb is the Harry and Catherine Jaynne Boand Endowed Professor of Chemistry and Biochemistry at the University of Washington in Seattle. Gelb received his B.S. degree from the University of California, Davis and his Ph.D. with Stephen G. Sligar at Yale University on aspects of the catalytic mechanism of cytochrome P450. Granted an American Cancer
continued on page 13
The Nucleus April 2013 5

NESACS 8th Annual Golf Tournament

By Amy Tapper (Photos by Amy Tapper) In 2012, the 8th annual NESACS Golf Tournament was again held at Wedgewood Pines Country Club in Stow, MA. A total of 62 players participated in the scramble format tournament. The afternoon began with a box lunch followed by a shotgun start at 1 PM. The lunchtime is a good opportunity for players to practice their putting and chipping as well as to network with colleagues who travel from all over the US to attend this annual event. After the tournament, a cocktail hour is held, followed by a buffet dinner and awards ceremony. This year there was a three-way tie for first place with the winning score of 64 (8 shots under par). The winners were then determined by their score on the hardest holes (or highest handicap holes). The golfers on the first-place team were Damon Abernathy, Nick Fudula, Andrew Morbey, and Ed Morbey. The golfers on the second-place team were Tae Cho, David Akeson, Dav Terro, and Sohan Abraham. The golfers on the third place team were Stu Needleman, Paul Defino, Nathan Barashansky, and Kevin Duffield. Prizes were also given for the longest drive and closest to the pin for both men and women. The mens long drive was won by John Green and the ladies by Angeles Dios. The mens closest-tothe-pin was won by Doug Saffran and the ladies by Cassandra Celatka. We are extremely grateful to the sponsors of this tournament. All proceeds from this tournament support NESACS programs. Over the past several years and again in 2012, our highest donor was the Lyophilization Services of New England (LSNE) (http://www.lyophilization.com). Our other generous sponsors who participated were: Aptuit (http://www.aptuit.com) Cambridge Major Laboratories (http://www.c-mlabs.com) Emerson Resources (http://www.emersonresources.com) IRIX Pharmaceuticals (http://www.irixpharma.com) Johnson Matthey Pharma Services (http://www.jmpharmaservices.com). Please visit their websites to investigate their services and capabilities We are looking forward to the 9th annual tournament, to be held on August 5, 2013 at the Kernwood CC in Salem, MA. u

First-place team (L-R)- Damon Abernathy, Edward Morbey, Andrew Morbey, Nick Fudala with tournament co-chair Harry Mandeville.

Second-place team- Tae Cho(R), David Akeson, Dav Terro, and Sohan Abraham(L)

Third-place team (L-R) Paul Defino, Stu Needleman, Kevin Duffield, Nathan Barashansky

Closest to the pin Doug Saffran with Harry Mandeville photos continued on page 11
6 The Nucleus April 2013

9th Annual NESACS Scramble Golf Tournament

2013 Tournament Co-Organized with PCI Synthesis
Kernwood Country Club
www.kernwoodcc.org Salem, MA August 5, 2013
BBQ Lunch followed by a Shot Gun Start at 1 PM Buffet Dinner and Awards Immediately Following

Cost: $170 per golfer

Greens fee, Cart Full BBQ lunch, snacks and drinks on the course, passed appetizers, and full buffet dinner with carving stations Prizes include longest drive, closest to the pin, first, second, and third place teams Hole Sponsorships are available at the suggested levels: $2500 $2000 $1500 $1000 $500 $300 Boron Osmium Sulfur Tritium Oxygen Nitrogen

Fee Includes:

Please note: hole sponsorships are very important. All proceeds support NESACS programs Registration: contact Harry Mandeville at h.mandeville@verizon.net. Please include all golfers names and e-mail addresses. Payment: by check only. Please send your check to: Harry Mandeville 7 Pillings Pond Road Lynnfield, MA 01940

The Nucleus April 2013

Summer Scholar Report

Towards an All-Atom Model for m-Poly(phenylene ethynylene) Class of Foldamers using the CHARMM27 Force Field: Structure and Unfolding Pathway of Foldamers of Various Lengths
Morris E. Cohen, Adam Moser, and Binyomin Abrams,* Department of Chemistry, Boston University, Boston MA * To whom correspondence should be addressed. E-mail: abramsb@bu.edu Current address: Loras College, Dubuque, IA Abstract An all-atom model for the m-Poly(phenylene ethynylene) (mPPE) class of foldamers was developed for the CHARMM27 force field. The folding behavior of mPPEs of different residue lengths with triethylene glycol exohelical side chains in explicit water were studied by all-atom molecular dynamics simulations with the CHARMM27 force field. mPPEs were studied in both the helical and extended conformations in water to find the minimum energy structures. The unfolding pathway and free energy landscapes of the foldamers were probed using metadynamics, in which the folded state was determined to be 8.5 and 16.3 kcal mol 1 more favorable in implicit solvent and explicit solvent, respectively. Introduction Biological macromolecules, such as proteins, lipids, and DNA self-assemble into compact solution structures. 1 Folded conformations are determined by temperature, hydrogen bonding, and van der Waals interactions. Due to the prevalence of folding in bio-macromolecules, a deep understanding of the folding process is of particular importance. 2 Consequently, significant work has been done to understand the fundamental science behind the folding process. 3 Because of the complex nature of proteins and other bio-macromolecules, compounds that mimic the way proteins behave have been sought out.4 Nonetheless, despite -helices being one of the most common protein structures,5 there exist relatively few synthetic molecules that mimic an -helix.1 This has led to the development of m-Poly(phenylene ethynylene) or mPPEs,6 oligomers that fold using noncovalent interactions between atoms to adopt a helical structure that is more thermodynamically favored in solution. J. Moore and others610 have shown that mPPEs with ester side chains and a residue length of 12 or more adopt a specific -helix conformation in acetonitrile and water. mPPEs have been both synthesized 7,11,12 and modeled,1315 but few are water soluble, which presents a significant limitation on their application to biological systems.9,16 Both Saven13 and Sen17 have independently shown that the folded -helix conformation is a minimum energy structure. Bruce and others12, 1820 have shown that mPPEs with small exohelical side chains ( COOMe, CONH2 , etc.) prefer a folded conformation over an extended conformation. Additionally, Elmer 21 has shown that mPPEs can get trapped in misfolded states during the folding process, similar to that of proteins. In this study, we examine the effect of residue length on the folding propensity of mPPE with triethylene glycol ester
8 The Nucleus April 2013

side chains (COOTg) in both explicit and implicit solvent. Moore has previously shown experimentally that an mPPE with residue length of eight will not fold, and a residue length of ten will form a semi-folded state.10 Additionally, the free energy landscape of unfolding was investigated using metadynamics, an accelerated sampling method used to study free energy surfaces and force systems out of local minima in molecular dynamics simulations.22 Parameterization of mPPE and Simulation Details

Figure 1: Structure of mPPE monomer. C8 is connected to C2 of the following unit. 1, 2, and 3 have monomer lengths of 8, 10, and 12, respectively. Triethylene glycol (Tg) side chains were used in this study.

Figure 2: Structure of tolane. The potential for the dihedral angle between the two benzene rings was calculated by Okuyama experimentally to be 0.6 kcalmol1.29

Table 1: Comparison of HF charges to the charges used for mPPE (atoms labeled in Figure 1)

Parameterization The potential energy term for the CHARMM force field23 is given by:

Summer Scholar
continued from page 8

Results and Discussion

where the force constants Kb, K, KUB, K, K are the bond, angle, Urey-Bradley, dihedral, and improper dihedral force constants, respectively; b, , s, , are the bond length, bond angle, Urey-Bradley distance, dihedral angle, and improper dihedral, respectively. Force field parameters for 3 (mPPE 12-mer, Figure 1) were either obtained from analogous residues in the CHARMM27 force field24 or were developed to fit experimental results and quantum mechanical calculations. The triethylene glycol side chain parameters were taken from the CHARMM ether force field. 25 The ester functional group parameters were taken from the CHARMM lipid parameters for deoxylysophosphatidyl-choline (LPPC).26 The triple bond carbon parameters were taken from the CGenFF parameters of 2-butyne.27 The benzene carbons and hydrogens were matched to the benzene parameters of phenylalanine.24 The missing charges (C2, C4, C6-8, Figure 1) were calculated using Gaussian0928 using HF/631G** basis set and fit to ensure charge neutral groups. The parameters for the dihedral, , between the two benzene planes (Figure 2) were derived from Gaussian09 HF/631G** calculations, and using experimental data of tolane,29 to produce the correct rotational potential energy surface. The ab initio torsional potential energy surface was obtained from a 90 rotational scan in 10 increments due to the periodicity of the potential energy surface. Parameters were then created K , n, and to match the potential energy surface. The best-fit parameters were determined to be a force constant K = 0.06 kcal mol1 rad2, periodicity n = 2, and = 180. Simulation Details Initial helical configurations of mPPE were generated using the CHARMM36 package and the new mPPE parameters. Explicit solvent simulations had one mPPE solvated in TIP3P water in truncated octahedra (8469 TIP3P waters and side of length of 80 for 3). Equilibration runs (500 ps) and production runs (10-50 ns) were performed using 1 fs integration timesteps using the NAMD2 package. 30 The NPT ensemble was generated using Langevin piston method at 1 atm with a piston temperature of 300 K, a piston period of 200 fs, and a damping time constant of 100 fs. Electrostatics were treated using Particle Mesh Ewald. Non-bonded interactions were calculated using a switching function between 12 and 14 . For implicit solvent simulations, Generalized Born Implicit Solvent modeling water as a dielectric continuum with a dielectric of 78.5 was used. Equilibration runs (1 ns) and production runs (100 ns) were performed using 1 fs integration timesteps using the NAMD2 package30 with langevin temperature control. An alpha cutoff of 16 was used for calculating Born radius. Non-bonded interactions were calculated using a switching function between 16 and 18 .

Table 2: Structural conformation data for mPPEs of different oligomer lengths. Rg refers to radius gyration of the mPPE backbone. The pitch refers to the average distance between the planes of benzenes six residues apart

Figure 3: Time evolution of Rg for 3 in explicit solvent beginning in the folded conformation (red) and extended-coil conformation (green). The extended-coil conformation collapses into a misfolded knotted structure that is not escaped for the rest of the simulation.

Figure 4: Time evolution of Rg for 3 in implicit solvent beginning in the folded conformation (red) and extended-coil conformation (green). The extended-coil conformation collapses into a semi-folded structure after 2 ns and eventually collapses into a misfolded state, which it does not escape.

Structure In explicit solvent, mPPEs 1-3 remained in the folded conformation throughout simulations up to 50 ns, and for simulations of 100 ns in implicit solvent. The time evolution of Rg for 3 is shown in Figure 3 (explicit solvent) and Figcontinued on page 10
The Nucleus April 2013 9

Summer Scholar
continued from page 9

ure 4 (implicit solvent). Rg remained constant at a value of nearly 6.5 (Table 2) for all three foldamers, in both explicit and implicit solvents, which indicates a strong favoring of the folded structure. The helix pitch, measured as the average distance between the planes of benzenes six residues apart, was determined to be 3.42 , which is consistent with the experimental value of 3.5 .10 Simulations of 3 beginning in a random coil show a sharp decrease in Rg at 12 ns in explicit solvent, which corresponds to a collapse in structure from an extended-coil into a misfolded structure (Figure 3). In implicit solvent, a semi-folded structure was achieved after 2 ns (Figure 4). Furthermore, a misfolded structure, with Rg equivalent to the folded structure, occurs at 30 ns and persists for the

Figure 5: Potential of mean force for 3 calculated using metadynamics on Rg collective variable, in explicit (red) and implicit (green) solvent. The folded state is found to be 8.5 kcal mol1 (implicit solvent) and 16.3 kcal mol1 (explicit solvent) more stable than the extended conformation.

remainder of the 100 ns simulation. While R g of 3 in implicit solvent beginning in an extended-coil eventually reaches that of the folded structure, examination of the structure shows a compressed, misfolded structure. Metadynamics The free energy associated with uncoiling of the mPPEs was determined using metadynamics 31 where a historydependent bias potential is used to fill the free energy surface (FES) over time and allow efficient sampling of the FES. The form of the bias potential on a collective variable is given as:

where W is the gaussian hill height and is the hill width. Rg was chosen as the collective variable to study the unfolding pathway ( W = 0.1 kcal mol 1, = 0.3 , and gaussians were added every 1000 steps). The folded conformations were the global minima in
10 The Nucleus April 2013

(1) Guichard, G.; Huc, I. Chem. Commun. 2011, 47, 59335941. (2) Vendruscolo, M.; Zurdo, J.; MacPhee, C. E.; Dobson, C. M. Phil. Trans. R. Soc. Lond. A. 2003, 361, 12051222. (3) Dobson, C. M. Nature 2003, 426, 884890. (4) Hecht, S., Huc, I., Eds. Foldamers: Structure, Properties,
continued on page 11

the free energy profiles along R g , in both explicit and implicit solvent, which is consistent with the experimental results (Figure 5). In explicit solvent, the folded conformation was found to be 16.3 kcal mol1 more stable than the extended-coil conformation. As expected, the implicit solvent model leads to increased sampling of the non-native states32 and the free energy of unfolding (8.5 kcal mol1 for 3 in implicit solvent) is significantly lower than that predicted by the explicit model. Furthermore, the minimum observed in implicit solvent was located at a slightly larger radius of gyration (Rg = 6.8) than in explicit solvent (Rg = 6.4), due to the fact that the helix in implicit solvent achieved a slightly larger helix radius before unfolding. Additionally, the broadening of the implicit solvent free energy well is due to the prevalence of thermodynamicallyfavorable semi-folded structures that occur with Rg near 7. Nonetheless, there is good qualitative agreement between the results for the unfolding pathway generated in implicit and explicit solvent. Conclusions In this paper, the parameterization of the mPPE class of foldamers is discussed. The new CHARMM parameters for mPPE have been shown to correctly reproduce the experimentally determined folded structure for oligomers of 8, 10, and 12 monomers. Simulations on these mPPEs starting in the folded conformation remain folded in both implicit and explicit solvent. Additionally, mPPEs starting in the extended-coil conformations collapse into mis-folded and semi-folded conformations, which are more stable than the extended-coil conformations. Free energy sampling from metadynamics further confirms that the folded conformation is preferred over the extended state by 8.5 and 16.3 kcalmol1 in implicit and explicit solvent, respectively. As expected, implicit solvent simulation underestimate the free energy of folding. Our results indicate that the mPPE model correctly predicts the equilibrium structure of the native state for oligomers of length 8-12 monomers and provides a free energy of unfolding that is consistent with the experimental results in acetonitrile. The relative free energies of unfolding of different length oligomers, and the relative free energies of unfolding in different solvents, deserve a separate study. Acknowledgementsx0 The authors gratefully acknowledge the support of the Boston University Undergraduate Research Opportunities Program, the Northeastern Section of the American Chemical Society, the Boston University Scientific Computing and Visualization Group, and the National Science Foundation. MC acknowledges the James Flack Norris and Theodore William Richards Undergraduate Summer Scholarship. References

2012 Golf Winners

continued from page 6

Closest to the pin Cassandra Celatka

Longest drive- John Green

Longest drive- Angeles Dios

Summer Scholar
and Applications; Wiley-VCH: Federal Republic of Germany, 2007. (5) de Oliveira Santos, J. S.; VoisinChiret, A. S.; Burzicki, G.; Sebaoun, L.; Sebban, M.; Lo- hier, J.-F.; Legay, R.; Oulyadi, H.; Bureau, R.; Rault, S. J. Chem. Inf. Model 2012, 52, 429 439. (6) Nelson, J. C.; Saven, J. G.; Moore, J. S.; Wolynes, P. G. Science 1997, 277, 17931796. (7) Prince, R. B.; Barnes, S. A.; Moore, J. S. J. Am. Chem. Soc. 2000 , 122 , 27582762. (8) Heemstra, J. M.; Moore, J. S. Org. Lett. 2004, 6, 659662. (9) Stone, M. T.; Moore, J. S. Org. Lett. 2004, 6, 469472. (10) Lahiri, S.; Thompson, J. L.; Moore, J. S. J. Am. Chem. Soc. 2000 , 122 , 1131511319. (11) Zhao, D.; Moore, J. S. J. Am. Chem. Soc. 2002, 124, 99969997. 7 (12) Nguyen, H. H.; McAliley, J. H.; Bruce, D. A. Macromolecules 2011, 44, 6067. (13) Lee, O.-S.; Saven, J. G. J. Phys. Chem. B 2004, 108, 1198811994. (14) Blatchly, R. A.; Tew, G. N. J. Org. Chem. 2003, 68, 87808785. (15) Tie, C.; Gallucci, J. C.; Parquette, J. R. J. Am. Chem. Soc. 2006 , 128 , 11621171. (16) Arnt, L.; Tew, G. N. Macromolecules 2004, 37, 12831288. (17) Sen, S. J. Phys. Chem. B 2002, 106, 1134311350. (18) Adisa, B.; Bruce, D. A. J. Phys. Chem. B 2005, 109, 75487556. (19) Adisa, B.; Bruce, D. A. J. Phys. Chem. B 2005, 109, 1995219959. (20) Nguyen, H. H.; McAliley, J. H.; III, W. R. B.; Bruce, D. A. Macromolecules 2010, 43, 5932 5942. (21) Elmer, S.; Pande, V. S. J. Phys. Chem. B 2001, 105, 482485.
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(22) Laio, A.; Gervasio, F. L. Rep. Prog. Phys. 2008, 71, 126601. (23) Brooks, B. R. et al. J. Comput. Chem. 2009, 30, 15451614. (24) MacKerell, A. D. et al. J. Phys. Chem. B 1998, 102, 35863616. (25) Vorobyov, I.; Anisimov, V. M.; Greene, S.; Venable, R. M.; Moser, A.; Pastor, R. W.; Alexander D. MacKerell, J. J. Chem. Theory Comput. 2007, 3, 11201133. (26) Klauda, J. B.; Venable, R. M.; Freites, J. A.; OConnor, J. W.; Tobias, D. J.; Mondragon- Ramirez, C.; Vorobyov, I.; Alexander D. MacKerell, J.; Pastor, R. W. J. Phys. Chem. B 2010, 114, 78307843. (27) Vanommeslaeghe, K.; Hatcher, E.; Acharay, C.; Kundu, S.; Zhong, S.;

Shim, J.; Darian, E.; Guvench, O.; Lopes, P.; I. Vorobyov, A. D. M. J. J. Comput. Chem. 2010, 31, 671690. (28) Gaussian09, Frisch, M. J. et. al. Gaussian, Inc., Wallingford CT, 2009. (29) Okuyama, K.; Hasegawa, T.; Ito, M.; Mikami, N. J. Phys. Chem. 1984, 88, 17111716. (30) Phillips, J. C.; Braun, R.; Wang, W.; Gumbart, J.; Tajkhorshid, E.; Villa, E.; Chipot, C.; Skeel, R. D.; Kale, L.; Schulten, K. J. Comput. Chem. 2005, 26, 17811802. (31) Laio, A.; Parrinello, M. Proc. Natl. Acad. Sci. USA 2002 , 99 , 1256212566. (32) Zhou, R. Proteins 2003 , 53 , 148161. u

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Cambridge Science Festival

Northeastern Section of the American Chemical Society http://www.nesacs.org
The Cambridge Science Festival, the first of its kind in the United States, is an annual ten series of daylong events based on science, technology, engineering & math (STEM). The Festival makes science accessible, interactive and fun! The schedule of events for April 1321, 2013 is: http://cambridgesciencefestival.org/2013Festival/2013ScheduleOfEvents.aspx A signature event is the Science Carnival on Sat. April 13, 2013. Schools supporting the event include MIT, Harvard, Suffolk University, Northeastern University and many more. The American Chemical Society (ACS), the worlds largest scientific society, with 164,000 members, and the Northeastern Section of the ACS will be represented.

12:00pm - 4:00pm

Come one, come all!! The annual Science Carnival of CSF is kicking off the Festival yet again this year, Bring curious minds of all ages! Check back for updates soon! Cost: Free

The Cambridge Science Festival is organized and run by the MIT Museum. The MIT Museum also has a program called Science on the Streets. This program uses researchers and innovators to engage audiences with their love of STEM to kids, families and adults attending cultural and community events throughout Massachusetts. Volunteers are needed. Prepared by Dr. Jack Driscoll, Chair, Public Relations, Northeastern Section of the ACS.
12 The Nucleus April 2013

DIRECTORY February Meeting

continued from page 4

Biographies
Michael H. Gelb continued from page 5

SERVICES

speaker. I am always amazed at what can get accomplished during the networking session. If you want to get involved, why not come to a monthly meeting. Meetings are most often held the second Thursday of each month. You can find the time, date and location in The Nucleus or on the NESACS website (nesacs.org). We have some very interesting industrial and academic people at these meetings. We also have many active committees and need more volunteers. u

Calendar
continued from page 16

Apr 23

Prof. Sam Thomas (Tufts University) Brandeis, Gerstenzang 121 4:00 pm Prof. David Moore (Lehigh University) Using cryogenic spectroscopy to elucidate interactions of reactant molecules with nanocatalyst materials Tufts, Room P-106 4:30 pm Prof. Michael Jennings (University of Alabama) Total Syntheses of -and -C-glycoside Natural Products via Oxocarbenium Cations UNH Room N104 (formerly L103) 11:10 am Prof. David Moore (Lehigh University) Using cryogenic spectroscopy to elucidate interactions of reactant molecules with nanocatalyst materials Tufts, Room P-106 4:30 pm

Apr 24

Prof. Ted Betley (Harvard University) MIT, 6-120 4:15 pm Prof. Hannah Sevian (Boston University) Developing a Learning Progression on Chemical Design UNH Room N104 (formerly L103) 11:10 am Prof. Matthew S. Sigman (University of Utah) Prof. Jonathan Ellman (Yale University) MIT, 6-120 4:00 pm

Apr 25

Society postdoctoral fellowship, he then investigated mechanism-based inactivators of serine proteases and developed fluorinated ketones as tightbinding inhibitors of several classes of proteases working with Robert H. Abeles at Brandeis University. His current research interests include: 1) Studying the function and regulation of a group of enzymes called phospholipase A2 that are involved in lipid mediator biosynthesis related to inflammation; 2) Antimalaria and anti-trypanosome drug discovery; 3) New technology for the newborn screening of enzyme deficiency diseases including lysosomal storage diseases. He is author of >350 scientific papers and several patents. Among his awards are the P. B. Hopkins Faculty Award, the Medicines for Malaria Venture Project of the Year Award, The ICI Chemicals Excellence in Chemistry Award, The Pfizer Award from the American Chemical Society, and the Alfred P Sloan Fellowship Award. He was recently elected as a Fellow of the American Association for the Advancement of Science. u

Apr 30

Apr 26

Prof. Melanie Sanford (University of Michigan) WPI, Gateway Park, Rm. 1002 12:00 Noon

Apr 29

Prof. Eric Ferreira (Colorado State University) Brandeis, Gerstenzang 121 4:00 pm Prof. Wilfred A. van der Donk (University of Illinois at Urbana-Champaign) Phosphate Biosynthesis: A Treasure Trove for Novel Chemistry MIT, 56-114 4:00 pm

Prof. Eric Ferreira (Colorado State University) Boston College, Merkert 130 4:00 PM Prof. Basar Bilgicer (Notre Dame University) Multicomponent molecular design for therapeutic applications Tufts, Room P-106 4:30 pm Prof. Elizabeth M. Nolan (MIT) UNH Room N104 (formerly L103) 11:10 am

Notices for The Nucleus Calendar of Seminars should be sent to:

Sheila E Rodman, email: serodman(at)hotmail.com
The Nucleus April 2013 13

BUSINESS DIRECTORY
SERVICES SERVICES SERVICES

14

The Nucleus April 2013

BUSINESS DIRECTORY
SERVICES SERVICES CAREER SERVICES

Index of Advertisers
AsisChem, Inc. ....................14 Boston College ....................15 ChemDev Solutions ..............4 Eastern Scientific Co.............6 Front Run OrganX, Inc........14 Huffman Laboratories, Inc. .14 Mass-Vac, Inc.......................11 Micron Inc. ..........................14 New Era Enterprises, Inc.....14 NuMega Resonance Labs....14 Organix, Inc.........................14 PCI Synthesis ......................13 PolyOrg, Inc. .......................15 Rilas Technologies, Inc. ......15 Robertson Microlit Labs. ....14 Waters Corporation .............15
The Nucleus April 2013 15

Calendar
Check the NESACS home page for late Calendar additions: http://www.NESACS.org
Note also the Chemistry Department web pages for travel directions and updates.
These include: http://www.bc.edu/schools/cas/chemistry/semina rs.html http://www.bu.edu/chemistry/seminars/ http://www.brandeis.edu/departments/chemistry/ events/index.html http://www.chem.harvard.edu/courses/seminars. php http://chemcalendar.mit.edu/index.php http://chem.tufts.edu/seminars.html http://engineering.tufts.edu/chbe/newsEvents/se minarSeries/index.asp http://www.chem.umb.edu http://www.umassd.edu/cas/chemistry/ http://www.uml.edu/Sciences/chemistry/Seminar s-and-Colloquia.aspx http://www.unh.edu/chemistry/events

19 Mill Road Harvard, MA 01451

NONPROFIT ORG. U.S. POSTAGE PAID NORTHEASTERN SECTION AMERICAN CHEMICAL SOCIETY

ACS Northeastern Section at Fenway Park!

Red Sox Game 7:10pm, Friday, May 10th
In the return of a popular NESACS tradition, NESACS members, and friends of NESACS are invited to Fenway Park on Friday, May 10th to watch the Red Sox play the Toronto Blue Jays. Our right field grandstand seats are priced at $35 and include handling charges. These tickets will go fast! Reserve your seats by mailing your check (payable to NESACS) to Anna Singer, 12 Corcoran Road, Burlington, MA 01803. Questions (but not reservations) may be sent to secretary@nesacs.org. u

Prof. Richard P. Hsung (University of Wisconsin-Madison) LaMattina Lecture Series Ynamides: A Modern Functional Group In the New Millennium UNH, Room N104 (formerly L103) 11:10 am

Prof. Brandon Ashfeld (University of Notre Dame) MIT, 6-120 4:00 pm

Apr 15

Apr 03

Prof. Irwin Oppenheim (MIT) Boston College, Merkert 130 4:00 pm Prof. Thomas Meade (Northwestern University) Harvard, Pfizer Lecture Hall, 12 Oxford St., Cambridge, 02138 4:15 pm

Prof. Glenn Micalzio (The Scripps Research Institute) Pfizer Research Scientist TBA Harvard, Pfizer Lecture Hall 4:15 pm

Apr 16

Apr 04

Prof. David Reichman (Columbia University) Harvard, Pfizer Lecture Hall, 12 Oxford St. 5:00 pm Prof. Erick Carreira (ETH, Zurich) MIT, 6-120 4:00 pm

Prof. Erin Carlson (University of Indiana) Boston College, Merkert 130 4:00 pm Prof. Scott Phillips (Pennsylvania State University) New strategies in reagent design for point-ofuse diagnostics Tufts, Room P-106 4:30 pm Prof. Nicolay Tsarevsky (Southern Methodist University) UNH, Room N104 (formerly L103) 11:10 am

Apr 08

Prof. Gong Chen (Penn State University) Brandeis, Gerstenzang 121 4:00 pm

Apr 17- Apr 18

Apr 10

Davison Inorganic Chemistry Seminar Prof. Gerard Ferey (Universite de Versaille) MIT, 6-120 4:15 pm

Prof. Chao-Jun Li (McGill University, Montreal, QC. Exploration of New Reactivities for Synthetic Efficiency Northeastern, 129 Hurtig Hall 12:00 pm

Apr 18

Apr 01

Prof. Douglas Stephan (University of Toronto) Harvard, Pfizer Lecture Hall, 12 Oxford St 4:15 pm

Apr 11

Apr 02

Prof. Daniel J. Weix (University of Rochester) No More Nucleophiles: Direct, Selective Cross Coupling of Electrophiles Boston College, Merkert 130 4:00 pm Prof. David Crich (Wayne State University) Stereocontrolled glycosidic bond formation: A challenge and an inspiration for organic chemists Tufts, Room P-106 4:30 pm

Prof. Phillip Geissler (University of California Berkeley) Harvard, Pfizer Lecture Hall, 12 Oxford St. 4:15pm Prof. Olof Echt (UNH Physics) Adsorption on Aggregates of Fullerenes: SiteSelective Storage Capacities and Adsorption Energies UNH Room N104 (formerly L103) 11:10 am Prof. Dr. Andreas Hirsch (Friedrich-AlexanderUniversitt Erlangen-Nrnberg, Germany) Chemical Functionalization of Synthetic Carbon Allotropes Boston College, Merkert 130 4:00 pm

Prof. Thomas Keyes (Boston University) Boston College, Merkert 130 4:00 PM Prof. Michael Jennings (Universityof Alabama; Tuscaloosa,AL) Synthesis of and --C--glycoside Natural Products via Oxocarbenium Cations Northeastern, 129 Hurtig Hall 12:00 pm Prof. Daniel Kirby UNH Room N104 (formerly L103) 11:10 am

Apr 22

Dr. Agnes Derecski (Air Products Inc.) Brandeis, Gerstenzang 121 4:00 pm Continued on page 13

Notices for The Nucleus Calendar of Seminars should be sent to:

Sheila E Rodman, email: serodman(at)hotmail.com