Proteins as Important Reactive Compounds in Drinking Water Treatment

Transcription

1 Proteins as Important Reactive ompounds in Drinking Water Treatment Junsung Kim, Guanghui Hua, Gladys Dave Makdissy, Reckhow John Mcellan, ynthia astellon, Darlene Amherst Buttrick University of Massachusetts - MA WRR onference 8 April 2008

2 Outline Formation of N-DBPs from NOM Occurrence haracteristics hemistry of selected End Products DHAN DHAD NDMA Reactivity of Specific Nitrogenous onstituents Amino Acids Proteins & others Key N-DBPs and Methods to be developed

3 Reactions with hlorine The THMs H The Precursors! HO + natural organics (NOM) Br H Br Br H Oxidized NOM and inorganic chloride Aldehydes hlorinated Organics TOX THMs HAAs Br Br H Br hloroform Bromodichloromethane hlorodibromomethane Bromoform

4 The Haloacetic Acids Br Br OOH OOH Br OOH Br Br OOH Br Trichloroacetic Bromodichloroacetic hlorodibromoacetic Tribromoacetic Acid Acid Acid Acid (TAA) H OOH H Br OOH Br H OOH Br Dichloroacetic Bromochloroacetic Dibromoacetic Acid Acid Acid (DAA)

5 N-DBPs we know about: end products ertain to come from N-organics when using free chlorine N & NBr Major types: 9 species yanogen Halides Haloacetonitriles Halonitromethanes NO hloropicrin (HP) 2 H Br Br N H N H N Br Dichloroacetonitrile Bromochloroacetonitrile Dibromoacetonitrile (DAN) (BAN) Special focus on these compounds because of large data set (DBAN) Trichloroacetonitrile (TAN) N

6 Why N-DBPs? Nitrogenous organics are generally quite reactive an be enhanced by chloramination Some evidence that they are major contributors to adverse human health effects of DBPs Very little is known about N-DBPs Analytical chemistry is more complicated

7 HO ytotoxicity Work of Michael Plewa DBP hemical ass IAA BAA TBAA hloroacetamide Trichloroacetonitrile 3-Iodo-3-bromopropenoic Acid DBAA MX DIAA DBAA BDAA BIAA BAA AA 2-Bromobutenedioic Acid 2,3-Dibromopropenoic Acid TAA DAA DBNM DBNM BNM TBNM BDNM 3,3-Dibromo-4-oxopentanoic Acid BNM 2-Iodo-3-bromopropenoic Acid 3,3-Dibromopropenoic Acid DNM NM TNM Tribromopropenoic Acid 2-Bromo-3-methylbutenedioic Acid hlorodibromomethane Bromoacetamide Dibromoacetamide Tribromopyrrole Bromate Dichloroacetamide Trichloroacetamide EMS +ontrol Other DBPs Iodoacetamide Haloacetamides Dibromoacetonitrile Bromoacetonitrile Iodoacetonitrile Bromochloroacetonitrile Haloacetonitriles Dichloroacetonitrile hloroacetonitrile Iodoform Halomethanes Halonitromethanes 3,3-Bromochloro-4-oxopentanoic Acid Bromoform hloroform Halo Acids Haloacetic Acids HO ell ytotoxicity as %½ Values (~L 50 ) Log Molar oncentration (72 h Exposure) July 2006

8 Quantitative Structure-Toxicity Models Lowest Observed Adverse Effect Level AWWARF report by Bull et al., 2007 Number of halogenated DBPs >1000 All Halo DBPs Halonitriles > > >1-10 >0.1-1 > Number of halonitriles Distribution of estimated chronic LOAELs, mg/kg day -1

9 hemistry of the end products DAN Surface Water Dichloroacetonitrile (μg/l) Loss of Residual hlorine Dose 2.5 mg/l 5 mg/l 10 mg/l Time (hrs)

10 H DAN N DHAN H N OH k 2 k 1 k 4 H 2 O O H N fast O Key intermediate oncentrations are well known OH H 2 O fast OH H fast NH OH H N O pka = 3.7 N--DAD anion DAD H NH 2 O (+II) S (+IV) H N--DAD NH O k 1-1 OH k 1-2 HO H NH 2 H NH OH O O fast fast OH NH 3 H O NH 2 DAA OH

11 Proposed Rate Law for DAN Hydrolysis and oxidation d k k OH = { + [ ] + k [ ( + I)]} dt k1 = 1.78 x10-7 ±0.35 x10-7 (s-1) k2 = 3.42 ±0.31 (M-1s-1) k3 = 1.30 x 10-1 ±0.08 x 10-1 (M-1s-1)

12 DAN half-life based on ph & HO hlorine Residual (mg/l) Hours 1 Day 3 Days 1 Week H 2 O 3 Weeks 1 Hour O - OH - 10 Minutes At 20 From Reckhow, Platt, MacNeill & Mcellan, 2001 Aqua 50:1:1-13 Degradation in DS observed to increase with increasing ph IR data: Obolensky & Frey, ph

13 Halamides ompounds Monohaloacetamides hloroacetamide, Bromoacetamide Dihaloacetamides Dichloroacetamide (DAD) Bromochloracetamide (BAD) Dibromoacetamide (DBAD) Trihaloacetamides trichloroacetamide & analogues hlorination byproducts Probably a bit less prevalent with chloramines Pre-oxidation will probably reduce subsequent formation

14 Haloacetamides Mostly from HANs: Measureable by G Haloaceton itriles hlorine Haloacetam ides Haloacetic Acids Free (f) N-Halogenated Forms ombined (c ) Sulfite Total (t)

15 DAD Halflife hlorine Residual (mg/l) 100 DAD Stability Minutes 1 Hour 8 Hours 1 Day 3 Days 1 Week HO Weeks ph Reducing onditions OH - 3 Days 1 Week 8 Hours 3 Weeks 1 Day 1 Hour

16 Nitrosamines NDMA: typically formed at greater levels with chloramination than with chlorination ontinues to form across DS? other nitrosamines (beyond NDMA) have been reported in chloraminated water Levels and mechanisms Earlier work: Valentine & Weinberg New mechanism: Mitch

17 Pathway to NDMA Role of Dichloramine and oxygen Based on recent work by Bill Mitch and colleagues Dichloramine H N N H 3 R H 3 Dimethyl(xx)amine PRODUTS R H N H O N N Monochloro Unsymmetric Dimethylhydrazine (UDMH-) N H 3 H 3 N O O Oxygen H 3 H 3 Nitrosodimethylamine (NDMA)

18 The Unnatural Precursor? Ranitidine (Zantac) 63% conversion to NDMA Schmidt et al., 2006 [WQT] Introduced in 1981, largest selling prescription drug by 1988 Stomach ulcers and esophageal reflux Mean concentration of 3000 ng/l estimated for raw municipal WW (national average) Sedlak 2005 AWWARF report 450 ng/l formation in raw WW expected Unknowns: how much does this persist in treatment and in the environment? 18

19 Reaction of UDMH Abbreviations DMD: dimethyldiazene TMT: tetramethyltetrazene FMMH: formaldehyde monomethylhydrazone FDMH: formaldehyde dimethylhydrazone DM: dimethylcyanamide DMF: dimethylformamide From: Mitch & Sedlak, 2002 [ES&T, 36:588]

20 The DBP Iceberg DHAAs THMs, THAAs IR ompounds 50 MWDS DBPs Stuart Krasner ~700 Known DBPs Susan Richardson Halogenated ompounds Non-halogenated ompounds

21 Organic Nitrogen Abundance Ratio to carbon Redrawn from Westerhoff & Mash, DO/DON (mg-/mg-n) Percentile

22 Ranges of Org-N by types Estimates from literature surveys Order of magnitude estimates for organic nitrogen in surface waters (all values in µg-n/l) assification 50%ile 90%ile 99%ile DON Free AA ombined AA Nucleic acids Amino Sugars Humic-N Others

23 Amino Acids and Proteins Simple Amino Acids some form THMs and HANs Highest reactivity for activated AAs Tyrosine & Tryptophan: activated aromatic ysteine: sulfhydryl group H 2 NH 2 H OOH Alanine Proteins many linked AAs; relatively unreactive polypeptide bonds Reactions with proteins occurs most readily on AA side chains HO H 2 NH 2 H OOH Tyrosine

24 Phenylalanine Tyrosine ysteine ystine Glutamine Tryptophan hlorine Demand More reactive than 10 most NOM hlorine Demand (mg/mg-) 2 Aquatic NOM Fractions Selected Amino Acids Whole Waters Fulvic Acid Humic Acid Precursor Weak Hydrophobic Acids Hydrophobic Neutral Hydrophobic Bases Hydrophilic Acids Hydrophilic Neutrals Hydrophilic Bases Methionine Aspartic acid Lysine Arginine Histidine Asparagine 0

25 Phenylalanine Tyrosine ysteine ystine Glutamine Tryptophan Methionine Aspartic acid Lysine Arginine Histidine Asparagine THM formation Precursor Hydrophobic Neutral Hydrophobic Bases Hydrophilic Acids Hydrophilic Neutrals Hydrophilic Bases Minor except for two Trihalomethane Formation (μg/mg-) Tryptophan Tyrosine Aquatic NOM Fractions Selected Amino Acids Whole Waters Fulvic Acid Humic Acid Weak Hydrophobic Acids

26 Phenylalanine Tyrosine ysteine ystine Glutamine Tryptophan Hydrophilic Acids Hydrophilic Neutrals Hydrophilic Bases Methionine Aspartic acid Lysine Arginine Histidine Asparagine Trihaloacetic Acid Like THMs Tryptophan Tyrosine Aquatic NOM Fractions Selected Amino Acids Precursor Trihaloacetic Acid Formation (μg/mg-) Whole Waters Fulvic Acid Humic Acid Weak Hydrophobic Acids Hydrophobic Neutral Hydrophobic Bases

27 Lysine Arginine Histidine Asparagine Glutamine Tryptophan Phenylalanine Tyrosine ysteine ystine Methionine Aspartic acid Dihaloacetic Acid Aspartic acid Precursor Dihaloacetic Acid Formation (μg/mg-) Histidine Asparagine Aquatic NOM Fractions 387 Selected Amino Acids Whole Waters Fulvic Acid Humic Acid Weak Hydrophobic Acids Hydrophobic Neutral Hydrophobic Bases Hydrophilic Acids Hydrophilic Neutrals Hydrophilic Bases

28 Lysine Arginine Histidine Asparagine Glutamine Tryptophan Phenylalanine Tyrosine ysteine ystine Methionine Aspartic acid Dihaloacetonitriles Aspartic acid Histidine Aquatic NOM Fractions 255 Precursor Selected Amino Acids 85 Dihaloacetonitrile Formation (μg/mg-) Whole Waters Fulvic Acid Humic Acid Weak Hydrophobic Acids Hydrophobic Neutral Hydrophobic Bases Hydrophilic Acids Hydrophilic Neutrals Hydrophilic Bases

29 Amino Acids From: Perdue & Ritchie,

30 Amino AA conc 2 ons. DBP Formation (µg/mg-) Acid (µm/mg-) (mg/mg-) TOX THM TAA DAA HANs Unkn TOX Glycine Alanine Valine Isoleucine Leucine Serine Threonine Methionine Aspartic acid Glutamic acid Lysine Ornithine Arginine Histidine Asparagine Glutamine Tryptophan Phenylalanine Tyrosine Total FAA Upper Limit Whole Waters Total FAA 4.1% 1.0% 0.4% 0.3% 1.9% 21.4% 0.7% Upper Limit 55.0% 12.9% 5.6% 4.6% 25.2% 285.0% 8.8%

31 Degradation pathways R 1 R 4 H N R2 R 3 R 1 X + Nu X N R2 R 4 R 3 R 1 =H X + Nu X X N R2 R 4 R 3 R 2 =H or OOH I II R 2 =H or OOH HX (O 2 ) R 1 =H HX (O 2 ) General scheme for carbonyl and cyano formation from chlorination of amines and amino acids (adapted from Nweke and Scully, 1989, and Armesto et al., 1998). R 1 NH 2 R 1 R 4 N III O R 3 R 4 R 3 V NH 2 X X + Nu X R 4 N IV R 4 =H N R 3 HX R 3 VI Monohalamine Pathway Dihalamine Pathway

32 N-chloro-organics Reactions of chlorine with organic amines R Primary amines HO HO NH2 R NH R N 2 Secondary amines R 2 2 HO NH R N Inorganic chloramines can transfer their active chlorine in a similar fashion

33 LFERs Log k HO (M -1 s -1 ) Amino Acids 1 o Amines 2 o Amines 3 o Amines Polypeptides Relationship between basicity and 2 nd order rate constants for reaction of HO with N- compounds Data Sources: Friend, 1956; Hussain et al., 1972; Isaac et al., 1983; Armesto et al., 1993; Armesto et al., 1994; Antelo et al., 1995; Abia et al., pk a

34 Degradation of Organic hloramines Parent Amine k obs (s -1 ) t ½ (min) Alanine 1.3E Glycine 1.4E Histidine 2.7E Leucine 1.6E Phenylalanine 2.2E Serine 2.4E reatinine 3.5E Glycine N acetyl 6.0E Glycine ethyl ester 2.3E Glycylglycine 1.0E Sarcosine 5.3E

35 Analysis of Organic N-chloramines Approach Seems well suited to L Prior efforts with G were not very successful Proposal e.g., tosyl derivatization Fast analysis with UPL Parallel detection and analysis by Post-column reaction with I and absorbance L/MS/MS

36 onclusions: from QSTR Research needs Group Example Occurrence Toxicology Haloquinones Organic N- haloamines Alkaloidal nitrosamines 2,6-dichloro-3-methyl-1,2- benzoquinone (DMBQ) Prioritize on range of stabilities and mutagenic activity N-nitrosonornicotine 1-Noxide yclopentenoic acids & MX-related 3,5-dichloro 1-hydroxy-4- ketocyclopent-2-enoic acid 1 2 MF 2 1 Halonitriles 2,3-Dichloropropenal (arc) 2,3-dibromopropionitrile (DT) 1 1

37 Summary There is a broad range of nitrogenous organic compounds in natural waters that are reactive with chlorine and produce both regulated and non-regulated DBPs Amino acids are generally reactive High hlorine demand Very high DHAN formation Moderate to high DiHAAs; low to moderate THMs & TriHAAs Proteins Rapid degradation at reactive sites Then slow degradation, leading to similar DBP profiles Toxic compounds that may be regulated could include Organic chloramines Halonitriles Alkaloidal nitrosamines

38 Acknowledgements Richard Bull UMass Research support Guanghui Hua Junsung Kim Hans Mentzen Sponsor AWWA Research Foundation Project #2867 RFP #4089

39 The End Special thanks to AWWARF