mechanistic research at york - chem-mechanism.ukchem-mechanism.uk/york_research.pdfmechanisms in...
TRANSCRIPT
Mechanistic research at York
Mechanisms in molecular interactions and self-assemblies
Victor Chechik Dave Smith
Victor ChechikMechanistic chemistry of free radicals (+ EPR spectroscopy) and nanostructures
• Free radical detection
• Harnessing free radicals for applications
• Organic magnetic materials
Latest raw data\pinene silica X data: +MS, 1.2min #148
0
200
400
600
Intens.
287.0 287.5 288.0 288.5 289.0 289.5 290.0 290.5 m/z
simulation
20 G
experiment
Methodology developing for the detection of free radical intermediates, e.g., based on spin trapping and EPR spectroscopy or MS (with Andrew Rickard).J. Am. Chem. Soc. 2009, 131, 7189; Science 2015, 349, 1072.
New approaches to synthetically-useful radical chemistry, e.g., radical initiation based on non-thermal plasmas or electrochemistry (with Deborah O’Connell, Peter O’Brien and Alison Parkin).Chem. Comm. 2017, 53, 3685; Chem. Eur. J. 2016, 22, 3496.
New chemistry of stable free radicals (with AnnMarie O’Donoghue) and applications to magnetic materialsNat. Comm. 2017, 15088.
• Understanding molecular structure/dynamics
in supramolecular/nanostructures by EPR spectroscopy
• Magnetic nanoparticles
• Nanoparticles in photocatalysis
10 G
Spin labels and EPR spectroscopy for characterisation of nanostructures (with Dave Smith).Soft Matter 2015, 11, 8968; Langmuir 2014, 30, 9210.
Iron and iron oxide micro and nanoparticles, e.g., for drug delivery applications (with Dept. Phys., Electronics and Biol at York).
Understanding the mechanisms of photocatalysis at the semiconductor nanoparticle surface, e.g., EPR spectroscopy to characterise charge carrier trapping at the surface (with Richard Douthwaite).
Dave SmithSupramolecular Nanomaterials
• Self-Assembled Hierarchical Multi-Component Materials
• Physical organic methods to understand & direct performance on multiple length-scales (molecular, nano, micro, macro)
• Applications: Tissue Engineering, Drug Formulation, Environmental Remediation, Soft Nano-Electronics
D. K. Smith and co-workers, J. Am. Chem. Soc. 2015, 137, 15486D. K. Smith and co-workers, Angew. Chem. Int. Ed. 2016, 55, 183
Supramolecular Nanomedicine
• Self-Assembled Multivalent (SAMul) Molecular Recognition
• Physical organic methods used to characterize and optimize binding in highly competitive biological environments
• Applications: Gene Delivery, Heparin Rescue for Coagulation Control, Cell-Surface Binding, Anti-viral Agents
SelfAssembly
BiomolecularRecognition
D. K. Smith and co-workers, Chem. Sci. 2014, 5, 1484D. K. Smith and co-workers, J. Am. Chem. Soc. 2015, 137, 10056
Mechanisms in metal catalysis, kinetics, photochemistry, in operando measurements
Simon Duckett Ian Fairlamb Jason Lynam Robin Perutz
John Slattery Alison Parkin Caroline Dessent
Ian Fairlamb
Mn catalysis (homogeneous) & C-H bond activation
Angewandte Chemie 2016 & 2015Full EPSRC Ind. CASE funding with
Syngenta (Mn catalysis)Full BBSRC Ind. CASE funding with
GSK (Biocatalysis)
Fairlamb group
Catalysis & Mechanism
Automation & Robotics
Biocatalysis & MetalCatalysis
Sustainable Synthesis
http://www-users.york.ac.uk/~ijsf1/index.html
Working with Jason Lynam and Rutherford Appleton Laboratories
Homogeneous-heterogeneous catalysts for cross-coupling reactions; C-H bond activation chemistry
• Nitrite/nitrate redox chem. at PdII/PdIV, C-H bond activation catalysis and functionalisation (J. Am. Chem. Soc. 2017)
• Mechanistic C-H bond activation in fluorinated organic –organometallic systems (Organometallics 2015)
• C-H bond functionalisation at Pd: use of robotic reaction screening and statistical analysis (new – supported by UoY/Wellcome Trust funding).
• Electrochemical activation of waste Pd (Newton Fund)
Internal collaborations: Duckett, Lynam, Perutz, Slattery and Wilson (Maths)External collaborations: Lin (HKUST), Ariafard (Tasmania), Eisenstein (Montpellier), Doherty (Newcastle), Willans (Leeds), Lee (Aston), Johnston (B’ham), EU + Pharma Ind., iPRD / Blacker & Bourne (Leeds)
C-H bond activation EU-COST action – CHAOS (catalysis-focus)EU-IMI-4 (Chem21), BayerCropScience (CASE Award) and Bruker (CASE Award); Chemspeed Robotics
• New cross-coupling Pd catalysts, including bimetallic complexes, Pdn clusters and Pd nanoparticles
• Natural product synthesis and peptide C-H bond functionalisation (Chem. Commun. 2015; Chem. Eur. J. 2015)
http://www-users.york.ac.uk/~ijsf1/index.html (Fairlamb)
Jason LynamUltrafast Spectroscopy as a Mechanistic Probe
Studying mechanism on a ps-ms timescale.Quantitative insight into the processes underpinning Mn-catalysis.Key intermediates in C-C bond formation observed.Effects of substrate and ligands quantified.
Fairlamb, Lynam and Towrie (RAL)
Mechanistic Insight into Organometallic Catalysis
Catalyst DeactivationProduct Isolated
New easily prepared catalyst precursor identified
MethodsIn situ spectroscopyIsotopic labellingKinetics(Organometallic) product isolationDensity Functional Theory
Informed by experiment, DFT identifies novel mechanistic steps
EPSRC Grant EP/H011455/1 J. Am. Chem. Soc., 2013, 135, 2222. Dalton Trans., 2014, 43, 4565. Lynam and Slattery
John SlatteryOuter-sphere electrophilic fluorination (OSEF)
Slattery and Lynam
Patent Appl. WO2016/087879A1J. Am. Chem. Soc., 2015, 137, 10753. Dalton Trans., 2016, 45, 1717.Angew. Chem. Int. Ed., 2017, DOI: 10.1002/anie.201702401R1
OSEF – A novel mechanism for metal-mediated C-F bond formation
Metal-mediated alkyne functionalization via OSEF
Mechanistic details – from NMR, UV/Vis and comprehensive DFT studies probing closed-shell and SET-based mechanisms
Slattery and collaborators
e.g. Chem. Eur. J., 2016, 22, 3414.Dalton Trans., 2015, 44, 110.Dalton Trans., 2014, 43, 11277.J. Am. Chem. Soc., 2013, 135, 2222.
Computational mechanistic studiesDFT and ab initio methods for mechanistic studies in a range of areas
MGD
model
MGD
model
Trp179
Asp13
Ile142
Cys141
Arg606
Trp472
Trp293
Metalloenzymes:Acetylene hydratase
Self-assembled ligand systems
Main group chemistry
Ligand design
Tungsten-containing enzyme
Catalytic alkyne hydration facilitated by ligand-assisted proton shuttle (LAPS) steps
Ligand-exchange mechanism at PhE+ cations (E = S, Se)
Weak C-H…N H-bonds in solution
Alison ParkinExpanding and utilising the electrochemical toolkit
Expansion
• FT voltammetry: simultaneous measurement of electron-hopping and catalytic turnover
PNAS, FTV of Mo enzyme, 2015; Anal Chem, FTV of disulfide protein, 2016; JACS submitted, FTV of H2 biocatalysis
• Conductive surface chemistry to “wire” any redox-catalyst to any electrode
Angewandte, Conductive gels, 2016; Nat Comm, Si-Echem+photonics, 2016
Utilisation
• Redox-tagging drug molecules for triggered activation and monitoring
Inorg Chem, Fc-tagged CO-releasing molecules (with IJSF and JML), 2017
• Electro-synthesis
– late stage functionalisation (with PAOB and VC)
– CO2 mineralisation
Alison ParkinExpanding and utilising the electrochemical toolkit
Monitoring Reaction Mechanisms with Mass Spectrometry Interfaced with Laser
Spectroscopy
Dr Caroline Dessent
● Instrumentation unique in UK
● Commercial electrospray mass spectrometers custom-adapted to allow laser spectroscopy of mass-selected ions
● Bruker AmaZon and Bruker Esquire ESI-MS
Fig: Schematic of apparatus
(---laser UV/VIS OPO)
Current Capabilities
• Solution-phase reaction mechanisms probed via ESI-MS (reactants/products/intermediates)
• Solution-phase photochemical mechanisms probed via ESI-MS
• Products/intermediates identified via UV/VIS laser spectroscopy
• Direct monitoring of photochemical reaction mechanisms of isolated (gas-phase) systems (e.g. sunscreen photodegradation, Flavin photodegradation)
Planned Future Capabilities• IR-fingerprint detection
• Chiral molecule detection
References1. Locating the Proton in Nicotinamide Protomers via Low-Resolution UV Action
Spectroscopy of Electrosprayed Solutions, Edward Matthews and Caroline E. H. Dessent, JPC A, 46, 9209-9216, 2016.
2. UV laser photoactivation of hexachloroplatinate bound to individual nucleobases in vacuo as molecular level probes of a model photopharmaceutical, Edward Matthews,
Ananya Sen, Naruo Yoshikawa, Caroline E. H. Dessent, PCCP, 18, 15143, 2016.
Mechanisms in sustainable and applied chemistry
James Clark Mike North Peter O’Brien
Will Unsworth Paul Clarke
Levoglucosenone as a Bio-based Platform molecule
J H Clark et al; see for example Chem Comm., 2014, 9650
James Clark
Designing new bio-based solvents to match polarity gaps
J H Clark, et al, ChemSusChem,2016, 3503 ; Green Chem., 2017, DOI: 10.1039/C7GC00112F.
Mike North: Unprecedented Carbonato
Intermediates in Cyclic Carbonates Synthesis
• Complex 2 was subsequently detected when complex 1 was
treated with CO2 at 50 bar carbon dioxide pressure by m/z, IR, 1H NMR and 13C NMR spectra.
• Formation of carbonate complex predicted by DFT calculation.
• complex 1 is not Lewis acidic, complex 2 is Lewis acidic.
• Enantiomerically pure epoxides and deuterated epoxides were
employed in the study of the mechanism.
Adduct state Transition state Product state
M. North et al., Chem. Eur. J., 2014, 20, 15005; ChemSusChem 2016, 9, 791.
HSPiP for Greener Solid Phase
Organic Synthesis (SPOS)
• The ability of various green
solvents to swell common
SPOS resins has recently
been investigated.[1]
• Initial swelling results have
been used to predict
additional green solvents
using HSPiP software.
[1]. S. B. Lawrenson, M. North, F. Peigneguy, A. Routledge, Green Chem., 2017, 19, 952-962.
O’Brien Group Mechanistic Research
Mechanistic Interrogation of Organolithium Chemistry
DFTModelling
Mechanisticblack box
?N
Boc
+ R–Li
+
NNMe
New SyntheticMethodology
6Li/13C NMR Spectroscopyof RLi/diamine Complexes
In situ React IR Spectroscopy
y = -0.0237 ± 0.0011x - 3.4005R² = 0.9842
-7
-6.5
-6
-5.5
-5
-4.5
-4
-3.5
-3
0 30 60 90 120 150
ln[p
relith
iati
on
co
mp
lex A
]
time / sec
t1/2 = 29.2 (± 1.3) sec
y = -0.0079x ± 9.7x10-5 - 2.9465R² = 0.9964
-6
-5.5
-5
-4.5
-4
-3.5
-3
-2.5
0 50 100 150 200 250 300 350 400
ln[L
ihit
hia
ted
In
term
ed
iate
]
time / sec
t1/2 = 86.9 (± 1.1) sec
KineticAnalysis
ReactionConditions
O’Brien Group Mechanistic Research
Mechanistic Interrogation of Organolithium Chemistry
J. Am. Chem. Soc. 2010, 132, 15445
In situ IR and NMR Spectroscopy: Rotamers
J. Am. Chem. Soc. 2012, 134, 5300
6Li/13C NMR Spectroscopyof RLi/diamine Complexes
y = -0.0237 ± 0.0011x - 3.4005R² = 0.9842
-7
-6.5
-6
-5.5
-5
-4.5
-4
-3.5
-3
0 30 60 90 120 150
ln[p
relith
iati
on
co
mp
lex A
]
time / sec
t1/2 = 29.2 (± 1.3) sec
y = -0.0079x ± 9.7x10-5 - 2.9465R² = 0.9964
-6
-5.5
-5
-4.5
-4
-3.5
-3
-2.5
0 50 100 150 200 250 300 350 400
ln[L
ihit
hia
ted
In
term
ed
iate
]
time / sec
t1/2 = 86.9 (± 1.1) sec
In situ React IR Spectroscopy
J. Am. Chem. Soc. 2010, 132, 7260J. Am. Chem. Soc. 2016, 138, 651
LithiationRates
Correlating Theory with Experiment:Using DFT to Predict Reactivity
TrappingRates
Unsworth group published work
Unsworth and Taylor et al. Org. Lett. 2013, 15, 258
React IR- detection of N-acyliminium ions
React IR- Mechanistic/kinetic details• Ag-nanoparticle involvement• Synergistic Ag/silica relationship uncovered
Unsworth and Taylor et al. Angew. Chem. Int. Ed. 2016, 55, 13798
Unsworth group ongoing/future work
For background see: Chem. Eur. J. 2016, 22, 8777.
Successive Ring Expansion (SuRE) reactions in supramolecular chemistry
(e.g. catenanes, rotaxanes).
[Potential links to Durham ECRs, e.g. Avestro, Kitching, Mcgonigal
For background, see: Angew. Chem. Int. Ed. 2015, 54, 15794
Vinyl metal reactive intermediates
Understanding Stereodivergent Heterocycle SynthesisPaul A. Clarke
TBAF/AcOH gives the 2,6-trans-THP.
TFA gives the 2,6-cis-THP.
DFT and synthetic studies show that the 4-hydroxyl group essential for stereodivergence.
Chem. Sci. 2017, 8, 482
Prebiotic “Protocell” Mediated Carbohydrate SynthesisPaul A. Clarke and David K. Smith
Amino esters or amino nitriles embedded in “Protocells” made of simple dipeptide hydrogels or agarose are
catalytically active and promote the formation of 2-deoxy-D-ribose as well as other carbohydrates of prebiotic relevance.
Catalytically active hydrogels are also under investigation.
Mechanisms in enzyme catalysis and metalloproteins
Gideon Davies Martin Fascione Paul Walton
M. A. Fascione et al, Chem. Eur. J., 2012, 18, 321-333 “Do glycosyl sulfonium ions engage in neighboring group participation? A study of oxathiane glycosyl donors and the basis for their selectivity”
Martin Fascione: glycosylation mechanisms
M. A. Fascione et al, Chem. Eur. J., 2012, 18, 2987-2997 “Mechanistic studies on a sulfoxide transfer reaction mediated by diphenyl sulfoxide”
mechanistic carbohydrate chemistry
O
O
S
Ph
OMe
O
O
O
S
Ph
OMe
dr: 96:4
O[18O, 87%]
S
48%
Tf2OOSOTf S OTf
DCM2 equiv.
1 equiv.
-60°C ® rt
-60°C ® rt
DCM
"2:1 premix"
O i)
ii)S
O
O
S
Ph
OO
O
S
Ph
dr: 93:7
52%
-60°C ® rt
DCMO
i)
ii)S
"2:1 premix"
O
O
S
Ph
OSR
LPMO
CBM CBM
endo-G
exo-G
Cu
O2
e
CAZy classification AA9, AA10, AA11, AA13
Quinlan et al, Proc Nat Acad Sci 2011, 15079–15084. Frandsen et al, Nature Chem. Biol. 2016, 298–303.
Mechanisms of Cu-containing LPMOs(Walton and Davies)
Methods
MO #163
(β-LUMO 1)
MO #164
(β-LUMO 2)
Spectroscopy Theory
StructuresKinetics
Mechanisms in complex chemical processes and analysis of rich data
Lucy Carpenter Terry Dillon Mat Evans
Andrew Rickard Julie Wilson (Maths)
Terry Dillon - gas-phase organic oxidation
OH + RH (+ O2) H2O + RO2
RO2 = key intermediates - difficult to detect & budgets uncertainFurther RO2 chemistry terminates (1) or recycles key radicals (2)
RO2 + HO2 ROOH + O2 (1) OH + RO + O2 (2)
Experiments lasers generate RO2 & detect OH
Mechanistic info: rate constants; products;
isotope effects; speciated radical recycling info.
Applications: atmospheric / indoor air chem.;
biofuel combustion; autoignition...
Winiberg et al. , Atmos. Chem. Phys. 2016, 16, 4023-4042
Gross et al., J. Phys. Chem. A, 2014, 118 (6), 974–985
Taraborrelli et al., Nature Geos., 2012, 5, 190–193, 2012
Terry Dillon - mechanism validation
1. Reaction rates - experiments on multicomponent RH mixtures
X + RH products (X = OH, Cl,...)
• RH depletion by GC-TOF-MS
• ensemble relative rate analysis
rapid validation of kinetic database & SAR
new data for aromatics, large alkenes
2. Radical reactivity = k1[CH4] + k2[C5H8] + k3[NO2] + ...
Comparative Rate Method for OH &
Cl radicals (with York Plasma Institute)
test atmospheric models / measurements
Shaw et al. , Atmos. Chem. Phys. 2017 (in prep)
Sinha et al., Atmos. Chem. Phys. 2008, 8, 2213
SocietyKnowledge
EconomyTraining
AQ and Climate ResearchUnderpinned by detailed mechanistic understanding
Mechanism Development and
Evaluation
Field Observations
diagnostics and analysis tools
Modelling on a range of scales
Fundamental laboratory data
Chamber Evaluation £6M investment in buildings,
laboratories and equipment
Impact and translation
Master Chemical Mechanism
GEOS-ChemGlobal and
Regional Model
Fundamental chemistry
Field observations
Chamber Evaluationhttp://wacl.org.uk@AtmosChemYork
http://wacl.org.uk
Twitter: @AtmosChemYork
Case Studies• Evidence for renoxification in
the tropical marine boundary layer
• Halogens are an important NOx sink
• Potentially major impact on our understanding of oxidation chemistry Reed et al., Atmos. Chem. Phys., 17, 4081, 2017
HNO3 + aerosol → pNO3- + H+
pNO3 + hv → xHONO + yNO2
HONO + hv → OH + NO
NO NO2 NOx O3 HONO PAN
York’s Cape Verde observatory
• Atmospheric iodine levels influenced by sea surface emissions of inorganic iodine
• HOI and I2 production following the reaction of O3 with I− at the air–sea interface
• Microlayer enchantment
Carpenter et al., Nature Geoscience, 6, 108, 2013
http://wacl.org.uk
Twitter: @AtmosChemYork
Case Studies
• Iodine’s impact on tropospheric oxidants: a global model study in GEOS-Chem
• Newly implemented I chemistry + Br chemistry yield a tropospheric O3 burden decrease of 14.4 % and a small increase in OH (1.8 %) Sherwen et al., Atmos. Chem. Phys., 16, 1161, 2016
• Halogen chemistry reduces O3 radiative forcing• More active halogen chemistry in present day vs. preindustrial
Sherwen et al., Atmos. Chem. Phys., 17, 1557, 2017
length
of drought
Julie Wilson: data processing method development and statistical pattern recognition e.g. multivariate analysis applied in metabolomics and proteomics
Multivariate analysis applied to chemical synthesis
Synthesis of 5-phenylphenanthridin-6(5H)-one