David Hinks1, dhinks@ncsu.edu, Nelson Vinueza-Benitez1, David C Muddiman2, Antony J Williams3. (1) Department of Textile Engineering, Chemistry & Science, North Carolina State University, Raleigh, North Carolina 27695, United States, (2) Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695, United States, (3) Department of eScience, Royal Society of Chemistry, Wake Forest, North Carolina 27587, United States The synthetic organic chemistry industry arguably began with the commercialization of the first synthetic dye, Mauveine, by Sir William Henry Perkin in 1856. Throughout the next 150 years, research and development of dyes exploded in response to the growing demand for high performance colored products for multiple major industries, including textiles, plastics, coatings, cosmetics, and printing. While many thousands of prototype dyes have been designed, synthesized, characterized, and tested, most of the structural and property data have been kept from the open literature even though large segments of the colorant industry have matured and many high volume dyes are now off patent. This is unfortunate considering that dyes are of fundamental importance to a number of growing areas of science and technology, including solar energy capture, medicinal chemistry (e.g. photodynamic therapy for cancer treatment), biomarkers, environmental monitoring, security printing, and camouflage. The ability for all scientists to observe comprehensive dye structure-property relationship data could help advance the theoretical and practical understanding of the role of dyes in various complex systems. NC State University's recently formed Forensic Sciences Institute is building a dye library that will enable establishment of the first comprehensive cheminfomatics system for forensic trace evidence analysis of dyed materials, as well as a broad range of dye discovery projects. As part of this effort, NC State recently secured a remarkable donation of approximately 100,000 dye samples, spectra and performance data that were made by a leading chemical manufacturer over a period of more than 50 years. Significant parts of the library will be made available online for free. The scope and challenges in developing a digitized structural database will be reviewed. Once completed, the new library will provide all scientists with a powerful tool for dye discovery and knowledge.

1. Cheminformatics for
Dye Chemistry Research:
Bringing Online an Unprecedented
100,000 Sample Dye Library
March 19, 2014
David Hinks, Nelson Vinueza,
Antony J. Wi l l i a m s
D e p a r t m e n t o f Te x t i l e
E n g i n e e r i n g , C h e m i s t r y & S c i e n c e

2. TECS Department Core Competencies
Goals of this presentation
Core Research Competencies
• Share information on a new physical dye library resource
– Opportunities and cheminformatics challenges
• Gain feedback on ways to optimize its utility
• Make new connections for dye and dye-related research
• Springboard for new collaborations / research proposals

3. TECS Department Core Competencies
In the beginning
Core Research Competencies
• 1856 William Henry Perkin
– 18 yr old student of Hoffman’s
– Failed quinine synthesis
– Produced purple impurity
• All too familiar serendipity result
– First dye synthesis
patent
– Father of industrial
chemistry
http://colour.sdc.org.uk/perkin‐timeline/

4. TECS Department Core Competencies
In the beginning
Core Research Competencies
“Producing a New Coloring
Matter for Dyeing with a Lilac
or Purple Color Stuffs of Silk,
Cotton, Wool, or other
Materials”

5. TECS Department Core Competencies
Greenford Green Dyeworks
First chemical factory
Core Research Competencies
http://colour.sdc.org.uk/perkin‐timeline/

6. TECS Department Core Competencies
Ubiquitous synthetic dyes
Core Research Competencies
Traditional applications
• Textiles
• Paper
• Plastics
• Paints
• Cosmetics
• Photography
• Food
Research needed:
- toxicity
- life-cycle assessment &
environmental impact
- application efficiency

7. TECS Department Core Competencies
Functional Dyes
Core Research Competencies
Safety & visibility

8. TECS Department Core ComDpyeteensc ietso
hide by
Core Research Competencies

9. TECS Department Core Competencies
Core Research Competencies
Dyes as
pharmaceuticals
(photodynamic
therapy)

10. GTEroCSw Dinepga rAtmreenta Cso reo Cf oRmpeesteencaiersch in
Functional Dyes
Core Research Competencies
Dye-Sensitized
Solar Cells
Dyes as
pharmaceuticals
(photodynamic
therapy)
Security Inks

11. TECS Department Core Competencies
Functional Dyes
Core Research Competencies
Biomedical imaging
http://www.koheras.com/side9489.html

12. ETaECsStm Deapnar tmCehnte Cmoreic Caoml pCetoenmciepsany
Dyes Research
Core Research Competencies
• Formerly Eastman-Kodak
• R&D in dye chemistry
– Photographic business
– Synthetic fibers
– Designed, synthesized, and
tested 1000s of dyes
– Unpublished
– Exited textile dyes business in
1990s
Max Weaver
Eastman’s lead dye chemist

13. ETaECsStm Deapnar tmDeynte C oLreib Croamrpyetencies
Donation to NC State
Core Research Competencies
• All dye samples from Kingsport, TN research building
(0.1- 3 g samples)
• >250,000 dyed fabric and carpet samples
• >250,000 test data
• 100s of technical reports
• Text books
• Rare BIOS Reports

14. LToEcCaSt Dioepnartment Core Competencies
College of Textiles, NC State
Core Research Competencies

15. Textile Department of Textile Engineering, Engineering, Chemistry & Chemistry & Science
Science
Faculty
31 interdisciplinary
faculty
Chemists
Organic/ Analytical/
Physical
Engineers
Chemical/Mechanical/
Industrial/ Textile/
Aeronautical
Students
~485 undergraduates
• Polymer & Color Chemistry
• Textile Engineering
• Textile Technology
~50 Master’s students
~70 PhD students
• Fiber and Polymer Science
• Textile Technology
Management
15

16. TECS Department Core Competencies
Renovation
Core Research Competencies

17. TECS Department Core Competencies
Moving
Core Research Competencies

18. TECS Department Core Competencies
Installation
Core Research Competencies

19. BTriEtCisSh D eIpnatretmlelingt eConrec Ceo mOpbetjeenccietisve
Subcommittee (BIOS) Reports
Core Research Competencies
• Joint US-British investigation
• Interrogation of German chemists
• 1946-49

20. TeTEsCt SD Daeptaartment Core Competencies
Core Research Competencies
• Color fastness on variety of synthetic fabrics
• Photostability; sublimation stability

21. TeTEsCt SD Daeptaartment Core Competencies
Core Research Competencies
• Color fastness on variety of fabrics
• Photostability; sublimation stability
File #
Synthesis
Notebook #
Varying
concentrations
Photostability

22. TECS Department Core Competencies 98,000 prototype dyes
Core Research Competencies

23. TECS Department Core Competencies
500-600 samples per draw
Core Research Competencies

24. TECS Department Core Competencies
All major dye classes
Core Research Competencies
• Many
– Azo
– Anthraquinone
• Fewer
– Methine
– Nitrodiphenylamine
– Porphyrin/phthalocyanine
– NIR dyes & UV absorbers

25. TECS Department Core Competencies
Anthraquinone dyes
Core Research Competencies

26. TECS Department Core Competencies
Azo dyes
Core Research Competencies

27. TECS Department Core Competencies
Unusual dyes
Core Research Competencies

28. TECS Department Core Competencies
Unusual polymeric dyes
Core Research Competencies

29. TECS Department Core Competencies Large number of structures of potential
interest for multiple applications
• Methines
Core Research Competencies

30. TECS Department Core Competencies
The oldest compounds (1940s)
Core Research Competencies

31. TECS Department Core Competencies
The oldest compounds (~1940s)
Core Research Competencies
NB# 303A‐2C

32. HToEwCS w Deeplal rtpmreents Ceorrev Ceodm?petencies
Excellent undergrad training
Even the very old dyes appear to be quite pure
Core Research Competencies

33. TECS Department Core Competencies
How Core well Research preserved?
Competencies
Many of the more complex structures appear good quality

34. TECS Department Core Competencies
How well preserved?
Core Research Competencies
356.1485
[M+H]
410 nm

35. TECS Department Core Competencies
UV/Vis, Fluorescence
Core Research Competencies
1
2.5E+06
2.0E+06
1.5E+06
1.0E+06
5.0E+05
0.0E+00
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
250 350 450 550 650 750
Emission (CPS)
Absorbance
Wavlength (nm)
Dye 1
Dye 2
Dye 3
DYE 1E
DYE 2E
DYE 3E
Dyes
UV‐Vis Absorption Emission

max (nm) ε (M‐1 cm‐1) em (nm)
NCSU‐MWDL1 289; 493 (*) 3820; 8,390 584
NCSU‐MWDL2 283; 464 (*) 3360; 5,730 535
NCSU‐MWDL3 287; 474 (*) 3390; 6,200 545
2
3

36. STiEnCgSl eDe Cparrtymsentat Cl oXre- CRomapye tencies
Crystallography
Core Research Competencies
• Likely that none of the dyes have been characterized
crystallographically

37. TECS Department Core Competencies
Forensic Dye Database
Core Research Competencies
• No standardized database of dyes is available for the
criminal justice community
– Fibers analyzed via microscopy, uv/vis
microspectrophotometry, sometimes LC-MS
– Method development
• LC
• MS
• Raman
– Dye identification without destruction of evidence
– Statistical validation

38. DTeEtCrSo Dite Apaurtmtoenmt Cootriev Ceo mFpaetbenrciices
Collection (1955 – present)
Core Research Competencies

39. Mass Spectra of Disperse Blue 60
39
M+H+
O
O
2M+Na+
NH2
NH2
N
O
O
O
CH3
Disperse Blue 60

40. UV Spectra of Disperse Blue 60 _005
40
Disperse Blue 60
Manufacturer variance

41. Disperse Blue 60
Manufacturer variance
DB 60 – 005
Mobay Chemical Corp.
45000
40000
35000
30000
25000
20000
15000
10000
5000
0
[M+H]+
N
100 200 300 400 500 600 700 800 900
Ion Counts
m/z
380.1241
226.2162 781.2228
[2M+Na]+
O
O
NH2
NH2
O
O O CH3
50000
45000
40000
35000
30000
25000
20000
15000
10000
5000
0
[M+H]+
N
100 200 300 400 500 600 700 800 900
Ion Counts
m/z
394.1393
809.2531
320.2557
[2M+Na]+
O
O
NH2
NH2
O
O O
CH3
50000
45000
40000
35000
30000
25000
20000
15000
10000
5000
0
N
100 200 300 400 500 600 700 800 900
Ion Counts
m/z
408.1554
837.2854
257.1510
[M+H]+
[2M+Na]+
O
O
NH2
NH2
O
O O
CH3
41
Disperse Blue 60 production

42. Year Make Model
2006 Dodge Dakota
2007 Suburu Tribeca
2008 Buick Enclave
2009 Mitsubishi Eclipse
2009 Nissan Maxima
2010 Honda Element
2010 Honda Pilot
2011 Ford Fusion
2011 Mazda 6
2011 Volkswagen Jetta
42
Ford Fusion Automotive Fibers

43. 2011 Ford Fusion
2.5
2
1.5
1
0.5
0
‐0.5
‐1
0 2 4 6 8 10 12 14
Intensity
Time (min)
4.40
7.69
8.89 10.25
11.50
660 nm
43
Ford Fusion Black Fiber

44. 2011 Ford Fusion
660 nm
90000
80000
70000
60000
50000
40000
30000
20000
10000
0
226.2162
C.I. Disperse Blue 60
100 200 300 400 500 600 700 800 900
Ion Counts
m/z
380.1238
781.2216
324.2144
N
O
O
NH2
NH2
O
O O CH3
[M+H]+
[2M+Na]+
44
Ford Fusion Black Fiber

45. 2011 Ford Fusion
2.5
2
1.5
1
0.5
0
‐0.5
‐1
0 2 4 6 8 10 12 14
Intensity
Time (min)
4.40
7.69
8.89 10.25
11.50
660 nm
45
Ford Fusion Black Fiber

46. 2011 Ford Fusion
660 nm
50
45
40
35
30
25
20
15
10
5
0
OH
C.I. Disperse Blue 73
100 200 300 400 500 600 700 800 900
Ion Counts
m/z
377.1130
867.1765
423.1011
268.0841
[M+H]+
O
O
O
CH3
NH2
NH2 OH
[2M+Na]+
46
Ford Fusion Black Fiber

47. 2011 Ford Fusion
2.5
2
1.5
1
0.5
0
‐0.5
‐1
0 2 4 6 8 10 12 14
Intensity
Time (min)
4.40
7.69
8.89 10.25
11.50
660 nm
47
Ford Fusion Black Fiber

48. 2011 Ford Fusion
660 nm
60000
50000
40000
30000
20000
10000
0
O
O
HN
OH OH
100 200 300 400 500 600 700 800 900
Ion Counts
m/z
377.0771
489.3667
775.1277
228.2321
[M+H]+
[2M+Na]+
N+ O- O
C.I. Disperse Blue 77
48
Ford Fusion Black Fiber

49. 2011 Ford Fusion: C.I. Disperse Blue 77 vs. C.I. Disperse Blue 73
2.5
Disperse Blue 73 Disperse Blue 77
2.5
2
1.5
1
0.5
0
‐0.5
‐1
0 2 4 6 8 10 12 14
Intensity
Time (min)
4.40
7.69
8.89 10.25
11.50
2
1.5
1
0.5
0
‐0.5
‐1
0 2 4 6 8 10 12 14
Intensity
Time (min)
4.40
7.69
8.89 10.25
11.50
50
45
40
35
30
25
20
15
10
5
0
OH
100 200 300 400 500 600 700 800 900
Ion Counts
m/z
377.1130
867.1765
423.1011
268.0841
[M+H]+
O
O
O
CH3
NH2
NH2 OH
[2M+Na]+
60000
50000
40000
30000
20000
10000
0
O
O
HN
OH OH
100 200 300 400 500 600 700 800 900
Ion Counts
m/z
377.0771
489.3667
775.1277
228.2321
[M+H]+
[2M+Na]+
N+ O- O
49
Ford Fusion Black Fiber

50. Time-of-Flight Secondary Ion Mass Spectrometry
Analysis of dyed fibers without extraction
O
O
NH2
HN
SO3H
6000
4500
3000
1500
0
Dyed Nylon Cross Section
390 392 394 396 398
Intensity (a.u.)
m/z, Negative Ion

51. DTeEvCeS lDoeppamrtmeenntt Coofre C Cohmepmeteinncfieosrmatics
For Core Public Use
Research Competencies
Stage 1: Digitize and publish all structures on ChemSpider
Stage 1
Stage 2
Stage 3
Stage 2: Protocols for collaborative projects and funding
Stage 3: Education and Training Program (REU?)
Stage 4: Establish online interest group(s)
User-based identification of potential high value compounds
4
Stage 5
SAR Forensics Toxicology/Env
Textiles Solar Cells Biomedical
Stage 5: Purify and characterize (MAJOR CHALLENGE)

52. TECS Department Core Competencies
Acknowledgments
Core Research Competencies
• Eastman Chemical Company
– Max Weaver and team
– Stewart Witzeman
– Bob Maleski
• Graduate Students
– Min Li
– Guan Wang
– XiuzhuFei
– ShaFu
– Nanshan Zhang
– Ann Crawford
• Undergraduate Students
– Cody Zane
– Emily Lichtenberger
• NC State Staff
– Maqbool Hussain (Post Doc)
– Chuanzhen Zhou (Post Doc)
– Roger Sommer (Crystallography)
– Dzung Nguyen
• NC State Faculty
– David Muddiman
– Keith Beck
– Dieter Griffis

53. Thank You! dhinks@ncsu.edu